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  1. Ismail TS
    Med J Malaysia, 2009 Sep;64(3):250-5; quiz 256.
    PMID: 20527283 MyJurnal
    Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in COPD patients and place a large burden on healthcare resources. COPD patients with frequent exacerbations have accelerated decline in lung function, poorer health status and are at higher risk of mortality. The mainstay of treatment includes increasing short acting bronchodilator therapy and systemic glucocorticosteroids with or without antibiotics. Non invasive ventilation is indicated in those with respiratory failure with acidosis or hypercapnia. Preventive strategies to reduce exacerbations include smoking cessation, immunisation against influenza and S. pneumonia, chronic maintenance inhaled pharmacotherapy, pulmonary rehabilitation and self management education.
  2. Ab Rahim SN, Omar J, Tuan Ismail TS
    Ann Pediatr Endocrinol Metab, 2020 Sep;25(3):152-155.
    PMID: 32871650 DOI: 10.6065/apem.2040004.002
    The gonadotropin-releasing hormone (GnRH) stimulation test is a valuable tool in diagnosing and differentiating causes of early pubertal occurrences. Utility of the test can be limited in some instances, however, including the early phases of pubertal hypothalamic-pituitary-gonadal axis activation, in girls showing commonly overlapping pictures, and in obese children due to excess circulating estrogen that suppresses luteinizing hormone (LH). A lack of consistent baseline and stimulated gonadotropin cutoffs observed in different studies also contributes to limitations in testing. Nevertheless, early detection of true pathological causes for pubertal disorders is needed to allow prompt treatment and better prognosis. While basal LH can be beneficial as a good screening tool for detecting pubertal disorder, it does not preclude the need for GnRH testing. The aim of this review was to highlight the role of GnRH stimulation tests and varying testing cutoffs in diagnosis of precocious puberty and its classification.
  3. Wan Azman WN, Omar J, Koon TS, Tuan Ismail TS
    Oman Med J, 2019 Mar;34(2):94-98.
    PMID: 30918601 DOI: 10.5001/omj.2019.19
    Pre-analytical quality in clinical chemistry testing is as important as analytical and post-analytical quality. The most prevalent pre-analytical interference and a major source of error producing unreliable laboratory test results is hemolysis of blood samples. In vitro hemolysis may be due to the blood withdrawal technique or sample handling whereas in vivo hemolysis can originate from acquired, hereditary, or iatrogenic conditions and is not technique dependent. Interpreting in vivo or in vitro hemolysis requires clinicians to supply reliable clinical history and findings. Even then, to reject or release the result with interpretation is still under debate. Thus, hemolyzed specimens are a serious pre-analytical problem calling for well-designed and strictly implemented laboratory guidelines. The aim of this non-systematic review (addressed to healthcare professionals) was to highlight the challenges in identifying and rejecting hemolysis specimens.
  4. Muid S, Abu Bakar NA, Abdul Rahman T, Tengku Ismail TS, Kholin SF, Suvorov AV, et al.
    Malays J Pathol, 2019 Dec;41(3):283-292.
    PMID: 31901913
    INTRODUCTION: Apart from inflammation and endothelial dysfunction, other key components in the development of atherogenesis include prothrombogenesis and oxidative stress. The effects of long-term confinement and isolation, exposure to radiation and different gravity forces during space travel could potentially increase the long-term risk of atherosclerosis. To the best of our knowledge, this is the first study determining the status of prothrombogenesis and oxidative stress in six cosmonauts subjected to the longest duration of confined isolation period of 520 days in preparation for prospective undetermined manned space travel to Mars.

    MATERIALS AND METHODS: This collaborative research between the National Space Agency (ANGKASA), Universiti Teknologi MARA, Malaysia and Institute of Biomedical Problems (IBMP), Russia was conducted at the Russian Academy of Sciences IBMP, Moscow, Russia. Six multi-national cosmonauts were assigned to live in a ground-based confined module for 520 days. Standard exercise and diet regime were instituted throughout the isolation phase. Six age, ethnic and gender-matched healthy, free-living ground controls were recruited in parallel. Serial serum and whole blood were analysed for biomarkers of prothrombogenesis [plasminogen activator inhibitor-1 (PAI-1) and homocysteine] and oxidative stress [oxidised low-density lipoprotein (ox-LDL) and malondialdehyde (MDA)].

    RESULTS: There were significantly lower concentrations of PAI-1 and homocysteine in cosmonauts during confinement compared to the controls. There were no significant differences seen in the concentrations of biomarkers of oxidative stress during confinement but there was a significant percentage change increment for serum MDA in cosmonauts.

    CONCLUSION: Long-term confinement decreased the risk of prothrombogenesis and this could be attributed to the exercise and diet regime which includes omega-3 fatty acids supplementation given to the crew members during their confinement period. However, oxidative damage could not be excluded and may be attributed to the influence of psychological stress during this prolonged confinement.

  5. Wan Nik WNFH, Zulkeflee HA, Ab Rahim SN, Tuan Ismail TS
    World J Diabetes, 2023 Jan 15;14(1):26-34.
    PMID: 36684386 DOI: 10.4239/wjd.v14.i1.26
    Insulin resistance increases the risk of developing diabetes, and the degree of resistance influences the glycemic control of patients with diabetes. Numerous researchers have focused on improving insulin sensitivity in order to prevent diabetes-related complications and other chronic diseases. Several studies have also linked vitamin D levels to insulin secretion and resistance, given that both vitamin D and its receptor complex play important roles in regulating pancreatic β-cells. It has been suggested that vitamin D supplementation improves vitamin D levels, but further research is needed to confirm this as neither insulin function nor glycemic control improves when vitamin D levels increase. Magnesium is a cofactor for many enzymes. Although the role of magnesium in the management of diabetes has long been evaluated, it has not yet been determined whether magnesium supplements improve insulin function. However, several researchers have found that patients with good glycemic control have high magnesium levels. Magnesium is closely related to vitamin D and is necessary for the transport and activation of vitamin D in humans. Combined supplementation with vitamin D and magnesium improves glycemic control in patients with diabetes.
  6. Ng WK, Philip AZ, Lim TT, Wong M, Goh EL, Tengku Ismail TS, et al.
    Med J Malaysia, 2023 May;78(3):350-356.
    PMID: 37271845
    INTRODUCTION: In managing hypertension, monotherapy and sometimes a combination of more than one agent are used to achieve blood pressure (BP) control. The objective of this prospective, observational, multi-centre study was to assess the level of BP control in patients receiving one or more anti-hypertensive drugs in private medical centres in Malaysia according to the treatment regimens (monotherapy, free drug combinations and single pill combinations).

    MATERIALS AND METHODS: Data were collected through medical records and interview sessions with patients on current pharmacotherapy for hypertension management at baseline and 2-3 months later. Results are expressed as mean ± SD for continuous data and as frequencies and percentages for categorical data.

    RESULTS: Among 182 recruited patients, 89 (49%) achieved BP control by the end of the study. Majority (62/89) patients were on single-pill (monotherapy or SPC) antihypertensives. Majority (63/89) required more than two antihypertensives to achieve BP control.

    CONCLUSION: Both SPC and free drug combination antihypertensives reduced BPs, but physicians preferred SPC to improve BP control and increase treatment compliance.

  7. Ong JC, W Omar WMH, Tuan Ismail TS, Chatterjee K, Hussain S
    J ASEAN Fed Endocr Soc, 2024;39(2):81-85.
    PMID: 39620185 DOI: 10.15605/jafes.039.02.04
    A three-year-old girl with a history of recurrent tonsillitis was investigated for failure to thrive and global developmental delay. Clinically, she had a triangular face with low-set ears and intermittent tachycardia. She had growth failure with her weight under the third centile while her height was within normal limits. Other systemic examinations were unremarkable. The presence of an elevated free T4 (FT4) with an inappropriately high thyroid stimulating hormone (TSH) in this patient raised the clinical suspicion of Thyroid Hormone Resistance Syndrome. DNA sequencing confirmed the diagnosis, which showed R243W gene mutation in Thyroid Hormone Receptor-Beta1 (THRB1).
  8. Che Soh NAA, Yaacob NM, Omar J, Mohammed Jelani A, Shafii N, Tuan Ismail TS, et al.
    PMID: 33171973 DOI: 10.3390/ijerph17218199
    Hyperprolactinemia (hPRL) often poses a diagnostic dilemma due to the presence of macroprolactin. Understanding the prevalence of macroprolactinemia (mPRL) has an important implication in managing patients with hPRL. The primary aim of this study was to determine the prevalence of mPRL globally and to explore selected factors influencing the prevalence estimate. Studies with original data related to the prevalence of mPRL among patients with hPRL from inception to March 2020 were identified, and a random effects meta-analysis was performed. Of the 3770 records identified, 67 eligible studies from 27 countries were included. The overall global prevalence estimate was 18.9% (95% CI: 15.8%, 22.1%) with a substantial statistical heterogeneity (I2 = 95.7%). The highest random effects pooled prevalence was observed in the African region (30.3%), followed by Region of the Americas (29.1%), European (17.5%), Eastern Mediterranean (13.9%), South-East Asian (12.7%), and Western Pacific Region (12.6%). Lower prevalence was observed in studies involving both sexes as compared to studies involving only female participants (17.1% vs. 25.4%) and in more recent studies (16.4%, 20.4%, and 26.5% in studies conducted after 2009, between 2000 and 2009, and before 2000, respectively). The prevalence estimate does not vary according to the age group of study participants, sample size, and types of polyethylene glycol (PEG) used for detection of macroprolactin (PEG 6000 or PEG 8000). With macroprolactin causing nearly one-fifth of hPRL cases, screening for mPRL should be made a routine before an investigation of other causes of hPRL.
  9. Zakaria WNA, Mohd Yunus N, Yaacob NM, Omar J, Wan Mohamed WMI, Sirajudeen KNS, et al.
    PMID: 33567588 DOI: 10.3390/ijerph18041595
    (1) Background: Several studies have suggested that the vitamin D receptor (VDR) gene plays a role in type 2 diabetes mellitus (T2DM) susceptibility. Nonetheless, the association between T2DM and VDR polymorphisms remains inconclusive. We determined the genotype of VDR rs1544410 (BsmI) and rs2228570 (FokI) polymorphisms among Malaysian patients with T2DM and their association with glycemic control factors (vitamin D levels, calcium, magnesium, and phosphate). (2) Methods: A total of 189 participants comprising 126 patients with T2DM (63 with good glycemic control and 63 with poor glycemic control) and 63 healthy controls were enrolled in this case-control study. All biochemical assays were measured using spectrophotometric analysis. VDR gene FokI and BsmI polymorphisms were analyzed using polymerase chain reaction and endonuclease digestion. (3) Results: Our findings revealed no significant differences in VDR FokI and BsmI genotypes between participants with T2DM and healthy controls. Moreover, no significant association was observed between both single nucleotide polymorphisms and glycemic control factors. Participants with poor glycemic control had significantly lower serum magnesium levels and significantly higher HOMA-IR compared to the other groups. (4) Conclusions: The present study revealed that VDR gene BsmI and FokI polymorphisms were not significantly associated with T2DM.
  10. Manap RA, Loh LC, Ismail TS, Muttalif AR, Simon GK, Toh RB, et al.
    PMID: 23185124 DOI: 10.2147/PROM.S19211
    BACKGROUND: Budesonide/formoterol used for both maintenance and reliever therapy has been shown to benefit patients with persistent asthma. We evaluated patient satisfaction and asthma control among Malaysian patients prescribed budesonide/formoterol as single maintenance and reliever therapy in a real-life clinical practice.
    METHODS: Adult patients diagnosed with partially controlled or uncontrolled asthma were recruited in a 6-month, prospective, open-label study involving ten hospital-based chest clinics in Malaysia. Patients were prescribed one or two inhalations of budesonide/formoterol Turbuhaler (160/4.5 μg per inhalation) twice daily as maintenance therapy and additional inhalation as reliever therapy. Maintenance doses were decided by physicians based on Global Initiative for Asthma-defined treatment objectives. The primary outcome measure was the change in mean Satisfaction with Asthma Treatment Questionnaire (SATQ) scores from baseline to an average of 3 months and 6 months. Secondary outcome was the change in mean Asthma Control Questionnaire 5-item version (ACQ-5) scores from baseline to an average of 3 months and 6 months and the proportion of patients achieving the minimum clinically important difference.
    RESULTS: Of 201 eligible patients recruited, 195 completed the study. Overall, SATQ mean (standard deviation) score was significantly improved from 5.1 (0.76) at baseline to 5.5 (0.58) (P < 0.001). The increase was observed in all domains of SATQ and had occurred at 3 months for most patients. ACQ-5 mean (standard deviation) score was significantly reduced from 2.2 (1.13) at baseline to 1.2 (0.95) (P < 0.001). A total of 132 (67.7.1%) patients had achieved the minimal clinically important difference (≥0.5) of ACQ-5 scores at study end.
    CONCLUSION: In a nationwide study, budesonide/formoterol maintenance and reliever therapy achieved greater patient satisfaction and better asthma control compared with previous conventional asthma regimes among Malaysian patients treated in a real-life practice setting. Such an approach may represent an important treatment alternative for our local patients with persistent asthma.
    KEYWORDS: Malaysia; Symbicort; asthma; asthma control; budesonide/formoterol; maintenance and reliever therapy; satisfaction
    Study site: Chest clinics, Hospitals, Malaysia
  11. Mohd Nasir S, Ismail AF, Tuan Ismail TS, Wan Abdul Rahman WF, Wan Ahmad WAN, Tengku Din TADA, et al.
    World J Exp Med, 2024 Mar 20;14(1):91271.
    PMID: 38590306 DOI: 10.5493/wjem.v14.i1.91271
    BACKGROUND: Diabetes is known damage the liver and kidney, leading to hepatic dysfunction and kidney failure. Honey is believed to help in lowering the blood glucose levels of diabetic patients and reducing diabetic complications. However, the effect of stingless bee honey (SBH) administration in relieving liver and kidney damage in diabetes has not been well-studied.

    AIM: To investigate the effect of SBH administration on the kidney and liver of streptozotocin-induced (STZ; 55 mg/kg) diabetic Sprague Dawley rats.

    METHODS: The rats were grouped as follows (n = 6 per group): non-diabetic (ND), untreated diabetic (UNT), metformin-treated (MET), and SBH+metformin-treated (SBME) groups. After successful diabetic induction, ND and UNT rats were given normal saline, whereas the treatment groups received SBH (2.0 g/kg and/or metformin (250 mg/kg) for 12 d. Serum biochemical parameters and histological changes using hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were evaluated.

    RESULTS: On H&E and PAS staining, the ND group showed normal architecture and cellularity of Bowman's capsule and tubules, whereas the UNT and MET groups had an increased glomerular cellularity and thickened basement membrane. The SBH-treated group showed a decrease in hydropic changes and mild cellularity of the glomerulus vs the ND group based on H&E staining, but the two were similar on PAS staining. Likewise, the SBME-treated group had an increase in cellularity of the glomerulus on H&E staining, but it was comparable to the SBH and ND groups on PAS staining. UNT diabetic rats had tubular hydropic tubules, which were smaller than other groups. Reduced fatty vacuole formation and dilated blood sinusoids in liver tissue were seen in the SBH group. Conversely, the UNT group had high glucose levels, which subsequently increased MDA levels, ultimately leading to liver damage. SBH treatment reduced this damage, as evidenced by having the lowest fasting glucose, serum alanine transaminase, aspartate transaminase, and alkaline phosphatase levels compared to other groups, although the levels of liver enzymes were not statistically significant.

    CONCLUSION: The cellularity of the Bowman's capsule, as well as histological alteration of kidney tubules, glomerular membranes, and liver tissues in diabetic rats after oral SBH resembled those of ND rats. Therefore, SBH exhibited a protective hepatorenal effect in a diabetic rat model.

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