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Group A Streptococcus puerperal sepsis with invasive neonatal infection: A fatal case

Siti Hafsyah MH, Ibrahim NR, Noraida R, Ismail AA, Anani Aila MZ, Hajissa K, et al.

Med J Malaysia, 2021 Sep;76(5):731-733.
PMID: 34508383

Neonatal invasive Group A Streptococcus (GAS) infection is a rare occurrence nowadays. Prior maternal vaginal colonization is an important factor in early neonatal disease. We report a case of invasive and fatal infection in a neonate. At Day 1 of life, a term baby was found to be lethargic, with poor feeding, and later became unresponsive. Consequently, the baby was immediately brought to the Emergency Department of Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan via ambulance. Despite the active resuscitation efforts in the hospital, the baby died. An autopsy was carried out to determine the cause of death. The mother was noted to have puerperal pyrexia secondary to vaginal discharge. Her high vaginal swab culture was positive for GAS. GAS was also isolated from the intracardiac blood, pleural fluid, peritoneal fluid, and umbilical swab of the baby, giving evidence to the aetiology of the mortality. Vaginal colonization of GAS is an important factor for high morbidity and mortality for both mother and infant due to its invasiveness and virulence.
Effect of rosiglitazone/ramipril on preclinical vasculopathy in newly diagnosed, untreated diabetes and IGT patients: 1-year randomised, double-blind, placebo-controlled study

Rahman S, Ismail AA, Ismail SB, Naing NN, Abdul Rahman AR

Eur J Clin Pharmacol, 2007 Aug;63(8):733-41.
PMID: 17565489 DOI: 10.1007/s00228-007-0315-3

OBJECTIVE: To investigate whether pharmacological interventions with rosiglitazone/ramipril can reverse preclinical vasculopathy in newly diagnosed untreated patients with type 2 diabetes (T2DM) and impaired glucose tolerance (IGT).

METHODS: In this randomised, double-blind, placebo-controlled study, 33 T2DM and 33 IGT patients were randomised to 4 mg rosiglitazone or 5 mg ramipril or placebo for 1 year. The subjects were newly diagnosed, untreated, normotensive, nonobese, nonsmoker, and nonhyperlipidaemic. Haemodynamic variables were measured at three treatment phases and pulse wave velocity (PWV) and augmentation index (AI) were measured throughout the treatment period.

RESULTS: Rosiglitazone showed a significant reduction in PWV (p=0.039) and AI (p=0.031) and ramipril demonstrated a significant reduction of AI (p=0.025) in IGT in comparison to placebo on the 12th month of treatment. No significant difference was observed in PWV and AI in T2DM with rosiglitazone/ramipril in comparison to placebo during overall treatment period.

CONCLUSIONS: Rosiglitazone significantly reversed preclinical vasculopathy in IGT as evident by significant decrease in PWV and AI after 1 year of treatment. Ramipril also reduced large artery stiffness as shown by significant decrease of AI after 1 year of treatment in IGT. Further trials are needed for a longer period of time, maybe with higher doses, to show whether rosiglitazone/ramipril can reverse preclinical vasculopathy in T2DM.
Fulltext Insulin sensitivity and secretory status of a healthy malay population

Al-Mahmood AK, Ismail AA, Rashid FA, Wan Bebakar WM

Malays J Med Sci, 2006 Jul;13(2):37-44.
PMID: 22589603 MyJurnal

Insulin insensitivity is a common finding in several metabolic disorders including glucose intolerance, dyslipidemia, hyperuricemia and hypertension. Most of the previous studies on insulin sensitivity were performed on diabetic or obese population. So our knowledge about insulin sensitivity of healthy population remains limited. Rising prevalence of obesity, diabetes and metabolic syndrome is a serious issue in Malaysia and some other rapidly developing countries. So it is important to look at the insulin sensitivity status of healthy Malaysian subjects and to compare it in future with those of diabetic, obese or metabolic syndrome patients. In this study we sampled subjects who were independent of confounding factors such as obesity (including abdominal obesity), hypertension and glucose intolerance (diabetes, IGT or IFG) which may influence insulin sensitivity. Fasting plasma glucose, fasting insulin and lipid profile were determined. Insulin sensitivity and secretory status were calculated using the homeostasis model assessment (HOMA) software (HOMA%S, HOMA%B and HOMA-IR). The insulin sensitivity (HOMA%S) of healthy Malay subjects aged between 30-60 years was 155.17%, HOMA-IR was 1.05 and HOMA%B was 116.65% (values adjusted for age, sex, BMI and waist circumference). It was seen that non-obese Malaysians can prevent age related lowering of insulin sensitivity if they can retain their BMI within limit.
Study site: 7 schools and 2 public offices in Kota Bharu, Kelantan, Malaysia
The effects of anti-obesity intervention with orlistat and sibutramine on microvascular endothelial function

Al-Tahami BA, Ismail AA, Bee YT, Awang SA, Salha Wan Abdul Rani WR, Sanip Z, et al.

Clin. Hemorheol. Microcirc., 2015;59(4):323-34.
PMID: 24002121 DOI: 10.3233/CH-131765

INTRODUCTION: Obesity is associated with impaired microvascular endothelial function. We aimed to determine the effects of orlistat and sibutramine treatment on microvascular endothelial function, anthropometric and lipid profile, blood pressure (BP), and heart rate (HR).
METHODS: 76 subjects were recruited and randomized to receive orlistat 120 mg three times daily or sibutramine 10 mg daily for 9 months. Baseline weight, BMI, BP, HR and lipid profile were taken. Microvascular endothelial function was assessed using laser Doppler fluximetry and iontophoresis process. Maximum change (max), percent change (% change) and peak flux (peak) in perfusion to acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis were used to quantify endothelium dependent and independent vasodilatations.
RESULTS: 24 subjects in both groups completed the trial. After treatment, weight and BMI were decreased for both groups. AChmax, ACh % change and ACh peak were increased in orlistat-treated group but no difference was observed for sibutramine-treated group. BP and total cholesterol (TC) were reduced for orlistat-treated group. HR was reduced for orlistat-treated group but was increased in sibutramine-treated group.
CONCLUSION: 9 months treatment with orlistat significantly improved microvascular endothelial function. This was associated with reductions in weight, BMI, BP, HR, TC and low density lipoprotein cholesterol. No effect was seen in microvascular endothelial function with sibutramine.
KEYWORDS: Microvascular endothelial function; obesity; orlistat; sibutramine
Fulltext Gene expression profiling in ethnic Malays with type 2 diabetes mellitus, with and without diabetic nephropathy

Lokman FE, Seman NA, Ismail AA, Yaacob NA, Mustafa N, Khir AS, et al.

J Nephrol, 2011;24(6):778-89.
PMID: 21360476 DOI: 10.5301/JN.2011.6382

BACKGROUND: Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD) among type 2 diabetes mellitus patients (DM) in Malaysia. This study used microarray analysis to determine the gene expression profiling in ethnic Malay patients with type 2 DM.
METHODS: A total of 312 patients were recruited; 25 were on dialysis due to ESRD, 128 were classified as normoalbuminuric, 93 as microalbuminuric and 66 as macroalbuminuric, based on urine albumin to creatinine ratio of <3.5, between 3.5 and 35 and =35 mg/mmol, respectively.
RESULTS: Microalbuminuria was associated with up- and down-regulation of 2,694 and 2,538 genes, respectively, while macroalbuminuria was associated with up-regulation of 2,520 genes and down-regulation of 2,920 genes. There was significant up-regulation of 1,135 genes and down-regulation of 908 genes in the ESRD samples. Thirty-seven significantly up-regulated genes and 40 down-regulated genes were commonly expressed in all 3 groups of patients with worsening of renal functions. Up-regulated genes included major histocompatibility complex (HLA-C), complement component 3a receptor 1 (C3AR1), solute carrier family 16, member 3 (SLC16A3) and solute carrier family 9 (sodium/hydrogen exchanger) (SLC9A8). Consistently down-regulated genes included were bone morphogenetic phosphatase kinase (BMP2K), solute carrier family 12, member 1 (SLC12A1), solute carrier family 7 (SLC7A2), paternally expressed 10 (PEG10) and protein phosphatase 1 regulatory (inhibitor unit) (PPP1R1C).
CONCLUSION: This study has identified several genes of interest, such as HLA-C, SLC16A3, SLC9A8, SLC12A1 and SLC7A2, that require verification of their roles as susceptibility genes for diabetic nephropathy in ethnic Malays with type 2 DM.
A simple and rapid genotyping method for beta-2 receptor (beta2 AR) gene using allele specific multiplex PCR

Romaino SM, Teh LK, Zilfalil BA, Thong CP, Ismail AA, Amir J, et al.

J Clin Pharm Ther, 2004 Feb;29(1):47-52.
PMID: 14748897 DOI: 10.1046/j.1365-2710.2003.00535.x

Polymorphism of the beta2-adrenergic receptor (beta2 AR) gene is an important determinant of the function of this receptor. It affects receptor down-regulation and beta2-agonist responses. It has also been a focus of interest in attempts to elucidate the genetic basis of asthma, hypertension, obesity and cystic fibrosis. Several different techniques have been established to determine beta2 AR genotypes but none of these methods are simple enough to detect simultaneously all the five alleles of our research interest (Arg16/Gly16, -20T/C, Gln27/Glu27, -47T/C and Thr164/Ile164).
Fulltext Metabolic and Inflammatory Changes with Orlistat and Sibutramine Treatment in Obese Malaysian Subjects

Al-Tahami BAM, Al-Safi Ismail AA, Sanip Z, Yusoff Z, Shihabudin TMT, Singh TSP, et al.

J Nippon Med Sch, 2017;84(3):125-132.
PMID: 28724846 DOI: 10.1272/jnms.84.125

INTRODUCTION: Obesity is associated with numerous health problems, particularly metabolic and cardiovascular complications. This study aimed to assess the effects that, nine months of pharmacological intervention with orlistat or sibutramine, on obese Malaysians' body weight and compositions, metabolic profiles and inflammatory marker.
METHODS: Seventy-six obese subjects were randomly placed into two groups. The first group received three daily 120 mg dosages of orlistat for nine months (n=39), and the second group received a once daily 10 or 15 mg dosage of sibutramine for nine months (n=37). Baseline measurements for weight, body mass index (BMI), waist circumference (WC), body fat percentage (BF), visceral fat (VF), adiponectin, fasting plasma glucose (FPG), fasting insulin, pancreatic B cell secretory capacity (HOMA%B), insulin sensitivity (HOMA%S), insulin resistance (HOMA-IR) and serum high sensitivity C-reactive protein (hs-CRP) were performed and repeated during the sixth and ninth months of treatment.
RESULTS: Twenty-four subjects completed the trial in both groups. For both groups, weight, BMI, WC, BF, VF, HOMA-IR and hs-CRP were significantly lower at the end of the nine month intervention. However, there were no significant differences between the two groups for these parameters with nine months treatment. There was a significant decrease in FPG in orlistat group; while fasting insulin and HOMA%B reduced in sibutramine group. For both groups, there were also significant increases in adiponectin levels and HOMA%S at the end of the nine month intervention.
CONCLUSION: Nine months of treatment with orlistat and sibutramine not only reduced weight but also significantly improved BMI, WC, BF, VF, FPG, adiponectin, fasting insulin, HOMA%B, HOMA%S, HOMA-IR and hs-CRP. These improvements could prove useful in the reduction of metabolic and cardiovascular risks in obese subjects.
Maggot debridement therapy to treat hard-to-heal diabetic foot ulcers: a single-centre study

Nair HK, Ahmad NW, Ismail AA, Alabed AAA, Zheming BO, Kaur G, et al.

J Wound Care, 2021 12 01;30(Sup12):S30-S36.
PMID: 34882006 DOI: 10.12968/jowc.2021.30.Sup12.S30

OBJECTIVE: Maggot debridement therapy (MDT) has seen a resurgence in recent years in the treatment of hard-to-heal wounds, as a result of rising antibiotic resistance. The sterilised larvae of Lucilia cuprina have been used in MDT in Malaysia since 2003, with encouraging results for the treatment of hard-to-heal diabetic wounds. We report a case series of 30 patients selected from our clinic by convenient sampling with diabetic lower limb ulcers treated with MDT. The average age of patients receiving MDT was >50 years. Of the 30 patients in the study, nine were female and 21 were male. All patients had underlying diabetes, two patients had leg ulcers and 28 patients had diabetic foot ulcers. Sterilised Lucilia cuprina larvae were applied via a standard method of 10 maggots per square centimetre and dressed with sterile gauze. The study endpoint was defined as ≤5% coverage with slough or necrotic tissue following three successive applications of MDT. In this study, maximum debridement of wounds was achieved in 96.6% (29 patients) of our patients, with ≤5% coverage with slough or necrotic tissue, in addition to a reduction in wound-related pain, as assessed by a visual analogue scale. No adverse events were reported. The findings of this study support the use of MDT as a safe, efficacious, and cost-effective method of managing diabetic wounds.
Fulltext Host immune response against DENV and ZIKV infections

Sekaran SD, Ismail AA, Thergarajan G, Chandramathi S, Rahman SKH, Mani RR, et al.

Front Cell Infect Microbiol, 2022;12:975222.
PMID: 36159640 DOI: 10.3389/fcimb.2022.975222

Dengue is a major public health concern, affecting almost 400 million people worldwide, with about 70% of the global burden of disease in Asia. Despite revised clinical classifications of dengue infections by the World Health Organization, the wide spectrum of the manifestations of dengue illness continues to pose challenges in diagnosis and patient management for clinicians. When the Zika epidemic spread through the American continent and then later to Africa and Asia in 2015, researchers compared the characteristics of the Zika infection to Dengue, considering both these viruses were transmitted primarily through the same vector, the Aedes aegypti female mosquitoes. An important difference to note, however, was that the Zika epidemic diffused in a shorter time span compared to the persisting feature of Dengue infections, which is endemic in many Asian countries. As the pathogenesis of viral illnesses is affected by host immune responses, various immune modulators have been proposed as biomarkers to predict the risk of the disease progression to a severe form, at a much earlier stage of the illness. However, the findings for most biomarkers are highly discrepant between studies. Meanwhile, the cross-reactivity of CD8+ and CD4+ T cells response to Dengue and Zika viruses provide important clues for further development of potential treatments. This review discusses similarities between Dengue and Zika infections, comparing their disease transmissions and vectors involved, and both the innate and adaptive immune responses in these infections. Consideration of the genetic identity of both the Dengue and Zika flaviviruses as well as the cross-reactivity of relevant T cells along with the actions of CD4+ cytotoxic cells in these infections are also presented. Finally, a summary of the immune biomarkers that have been reported for dengue and Zika viral infections are discussed which may be useful indicators for future anti-viral targets or predictors for disease severity. Together, this information appraises the current understanding of both Zika and Dengue infections, providing insights for future vaccine design approaches against both viruses.
Fulltext Metabolite Profiles of Red and Yellow Watermelon (Citrullus lanatus) Cultivars Using a 1H-NMR Metabolomics Approach

Sulaiman F, Ahmad Azam A, Ahamad Bustamam MS, Fakurazi S, Abas F, Lee YX, et al.

Molecules, 2020 Jul 15;25(14).
PMID: 32679913 DOI: 10.3390/molecules25143235

Watermelon, a widely commercialized fruit, is famous for its thirst-quenching property. The broad range of cultivars, which give rise to distinct color and taste, can be attributed to the differences in their chemical profile, especially that of the carotenoids and volatile compounds. In order to understand this distribution properly, water extracts of red and yellow watermelon pulps with predominantly polar metabolites were subjected to proton nuclear magnetic resonance (1H-NMR) analysis. Deuterium oxide (D2O) and deuterated chloroform (CDCl3) solvents were used to capture both polar and non-polar metabolites from the same sample. Thirty-six metabolites, of which six are carotenoids, were identified from the extracts. The clustering of the compounds was determined using unsupervised principal component analysis (PCA) and further grouping was achieved using supervised orthogonal partial least squares discriminant analysis (OPLS-DA). The presence of lycopene, β-carotene, lutein, and prolycopene in the red watermelon plays an important role in its differentiation from the yellow cultivar. A marked difference in metabolite distribution was observed between the NMR solvents used as evidenced from the PCA model. OPLS-DA and relative quantification of the metabolites, on the other hand, helped in uncovering the discriminating metabolites of the red and yellow watermelon cultivars from the same solvent system.
Predictors of ischaemic heart disease in a Malaysian population with the metabolic syndrome

Yeow TP, Khir AS, Ismail AA, Ismail IS, Kamarul Imran M, Khalid BA, et al.

Diabet Med, 2012 Nov;29(11):1378-84.
PMID: 22803824 DOI: 10.1111/j.1464-5491.2012.03741.x

AIMS: Cardiovascular disease is the foremost cause of mortality in Malaysia but little is known about the prevalence of the metabolic syndrome and its associations with other known cardiovascular risk markers. We undertook a population-based study to examine these.
METHODS: For the study, 4341 subjects were selected using a multistage stratified sampling method. Subjects were interviewed for personal and past medical history. Biomedical markers and anthropometric indices were measured. The metabolic syndrome was defined using the harmonized criteria. The associations between the metabolic syndrome and cardiovascular risk markers, including high-sensitivity C-reactive protein, microalbuminuria and HbA(1c) were examined.
RESULTS: The prevalence of the metabolic syndrome was 42.5%. Subjects with the metabolic syndrome are significantly more likely to have higher BMI (> 25 kg/m(2)), HbA(1c) [≥ 42 mmol/mol (6.0%)], LDL (≥ 2.6 mmol/l), elevated albumin:creatinine ratio (> 2.5 μg/mmol creatinine for men, 3.5 μg/mmol creatinine for women) and high-sensitivity C-reactive protein (> 3 mg/l); odds ratio 5.48, 6.14, 1.44, 3.68 and 1.84, respectively, P < 0.001. The presence of an elevated albumin:creatinine ratio and high-sensitivity C-reactive protein are strong predictors for the presence of a higher number of positive criteria of the metabolic syndrome. HbA(1c) > 48 mmol/mol (6.5%) is associated with increased relative risk of elevated albumin:creatinine ratio, high-sensitivity C-reactive protein and LDL (relative risk 3.10, 2.46 and 1.65 respectively, P < 0.001).
CONCLUSIONS: We confirmed the high prevalence of the metabolic syndrome in Malaysia. Our study revealed a strong relationship between risk markers of elevated BMI, HbA(1c), LDL, albumin:creatinine ratio and high-sensitivity C-reactive protein with the presence of the metabolic syndrome, putting them at a statistically high risk for cardiovascular mortality.
Fulltext Prevalence of abnormal glucose tolerance and risk factors in urban and rural Malaysia

Mustafa N, Kamarudin NA, Ismail AA, Khir AS, Ismail IS, Musa KI, et al.

Diabetes Care, 2011 Jun;34(6):1362-4.
PMID: 21498788 DOI: 10.2337/dc11-0005

OBJECTIVE:
To determine the prevalence of prediabetes and diabetes among rural and urban Malaysians.
RESEARCH DESIGN AND METHODS:
This cross-sectional survey was conducted among 3,879 Malaysian adults (1,335 men and 2,544 women). All subjects underwent the 75-g oral glucose tolerance test (OGTT).
RESULTS:
The overall prevalence of prediabetes was 22.1% (30.2% in men and 69.8% in women). Isolated impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were found in 3.4 and 16.1% of the study population, respectively, whereas 2.6% of the subjects had both IFG and IGT. Based on an OGTT, the prevalence of newly diagnosed type 2 diabetes was 12.6% (31.0% in men and 69.0% in women). The prediabetic subjects also had an increased prevalence of cardiovascular disease risk factors.
CONCLUSIONS:
The large proportion of undiagnosed cases of prediabetes and diabetes reflects the lack of public awareness of the disease.
Prevalence of metabolic syndrome and its risk factors in adult Malaysians: results of a nationwide survey

Mohamud WN, Ismail Aa, Khir AS, Ismail IS, Musa KI, Kadir KA, et al.

Diabetes Res Clin Pract, 2012 04;96(1):91-7.
PMID: 22553777 DOI: 10.1016/j.diabres.2011.11.020

Aim: To report the national prevalence of metabolic syndrome (MetS) and its risk factors among adult Malaysians (>18 years old) based on World Health Organization (WHO), the National Cholesterol Education Program Expert Panel III (ATP III), International Diabetes Federation (IDF) and the 'Harmonized' criteria.Methods: A multi-stage stratified sampling method was used to select 4341 subjects from Peninsular and East Malaysia. Subjects underwent physical and clinical examinations.Results: Based on the WHO, ATP III, IDF and Harmonized definitions, the overall crude prevalences of MetS were 32.1, 34.3, 37.1 and 42.5%, respectively. Regardless of the criteria used, MetS was higher in urban areas, in females, in the Indian population and increased significantly with age. Risk factors also increased with age; abdominal obesity was most prevalent (57.4%), was higher in females (64.2%) and was highest in Indians (68.8%).Hypertension was higher in males (56.5%) and highest among Malays (52.2%). In contrast,the Chinese had the highest prevalence of hypertriglyceridemia (47.4%).Conclusions: Malaysia has a much higher prevalence of MetS compared with other Asian countries and, unless there is immediate intervention to reduce risk factors, this may pose serious implications on the country's healthcare costs and services.
Fulltext Prevalence of overweight and obesity among adult Malaysians: an update

Wan Nazaimoon WM, Musa KI, Md Khir AS, Ismail AA, Ismail IS, Khalid BAK, et al.

Asia Pac J Clin Nutr, 2011;20(1):35-41.
PMID: 21393108

A total of 4428 adults (>18 years old) from 5 different selected regions in Peninsular and East Malaysia participated in this health survey. Using World Health Organization recommendations for body mass index (BMI), the prevalence of overweight and obesity were found to be 33.6% (95% CI= 32.2, 35.0) and 19.5% (95% CI= 18.3, 20.7) respectively. There were more females who were obese (22.5%, 95% CI=20.9, 24.0) compared to males (14.1%, 95% CI=12.3, 15.9). Highest prevalence of obesity were among the Indians (24.6%, 95% CI=20.3, 29.3), followed closely by the Malays (23.2%, 95% CI=21.6, 24.8%) and lowest prevalence was among the Chinese subjects (8.2%, 95% CI=6.2, 10.6). More than 43% of the 531 younger subjects (<30 years old) were either overweight (20%, 95% CI=16.6, 23.6) or obese (13.9%, 95% CI=11.1, 17.2%). All subjects who claimed to be non-diabetes were required to undergo 75 g glucose tolerance test. Compared to subjects with normal BMI (18.5-24.9 kg/m2), there was a 3- and 2-folds increase in the prevalence of newly diagnosed diabetes and impaired glucose tolerance respectively, among obese subjects (BMI>30 kg/m2) who initially claimed to have no diabetes. This study highlights a need for more active, inter-sectoral participation advocating a health-promoting environment in order to combat obesity in this country.

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