Displaying publications 1 - 20 of 250 in total

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  1. Tiong KH, Yiap BC, Tan EL, Ismail R, Ong CE
    Xenobiotica, 2010 Jul;40(7):458-66.
    PMID: 20402563 DOI: 10.3109/00498251003786749
    1. The effect of flavonoids on coumarin 7-hydroxylation, an activity marker of an important human liver cytochrome P450 isoform, cytochrome P450 2A6 (CYP2A6), was investigated in this study. 2. Coumarin 7-hydroxylase activity was measured fluorometrically in reaction mixtures containing cDNA-expressed CYP2A6, nicotinamide adenine dinucleotide phosphate generating system and 10 uM coumarin, at various concentrations of flavonoids. 3. Among the 23 compounds tested, most of the active members were from flavonol group of hydroxylated flavonoids, with myricetin being the most potent inhibitor followed by quercetin, galangin, and kaempferol. 4. Further exploration of the inhibition mechanism of these compounds revealed that myricetin, galangin, and kaempferol exhibited mixed-type of inhibition pattern while quercetin was observed to exhibit competitive mode of inhibition. 5. Structure-function analyses revealed that degree of inhibition was closely related to the number and location of hydroxyl groups, glycosylation of the free hydroxyl groups, degree of saturation of the flavane nucleus as well as the presence of the alkoxylated function.
  2. Ngow H, Teh LK, Langmia IM, Lee WL, Harun R, Ismail R, et al.
    Xenobiotica, 2008 Jun;38(6):641-51.
    PMID: 18570163 DOI: 10.1080/00498250801999087
    1. A retrospective study was conducted to explore the importance of CYP2C9 genotyping for the initiation and maintenance therapy of warfarin in clinical practice. A total of 191 patients on warfarin therapy in a local hospital were recruited after written informed consent. Their medical records were reviewed and no intervention of warfarin dose was performed. 2. A total of 5 ml of blood were taken from each subject for DNA extraction and identification of 1, 2, 3 and 4 CYP2C9 alleles, using a nested-allele-specific-multiplex-polymerase chain reaction (PCR). Half the patients were Malays and the remaining were Chinese. 3. Two genotypes were detected; 93.2% had CYP2C9 1/1 and 6.8% were CYP2C9 1/3. Warfarin doses were higher in patients with CYP2C91/1. Patients with the 1/3 genotype experienced a higher rate of serious and life-threatening bleeding; 15.4 versus 6.2 per 100 patients per 6 months. 4. The observation clearly highlights the inadequacy of the current dosing regimens and the need to move toward a more individualized approach to warfarin therapy. Prospective clinical studies are now being conducted to assess dosing algorithms that incorporate the contribution of the genotype to allow the individualization of warfarin dose.
  3. Nurfadhlina M, Foong K, Teh LK, Tan SC, Mohd Zaki S, Ismail R
    Xenobiotica, 2006 Aug;36(8):684-92.
    PMID: 16891249
    The genetically polymorphic cytochrome P450 (CYP) 2A6 is the major nicotine-oxidase in humans that may contribute to nicotine dependence and cancer susceptibility. The authors investigated the types and frequencies of CYP2A6 alleles in the three major ethnic groups in Malaysia and CYP2A6*1A, CYP2A6*1B, CYP2A6*1x2, CYP2A6*2, CYP2A6*3, CYP2A6*4, CYP2A6*5, CYP2A6*7, CYP2A6*8 and CYP2A6*10 were determined by allele-specific polymerase chain reaction (PCR) in 270 Malays, 172 Chinese and 174 Indians. Except for CYP2A6*2 and *3 that were not detected in the Malays and Chinese, all the other alleles were detected. Frequencies for the CYP2A6*4 allele were 7, 5 and 2%, respectively, in Malays, Chinese and Indians. A statistically significant high frequency of the duplicated CYP2A6*1x2 allele occurred among Chinese. Among Malays and Chinese, the most common allele was CYP2A6*1B, but it was CYP2A6*1A among Indians. These ethnic difference in frequencies suggested that further studies are required to investigate the implications on diseases such as cancer and smoking behaviour among these major ethnic groups in Malaysia.
  4. Ismail R, Kassim MA, Inman M, Baharim NH, Azman S
    Water Sci Technol, 2002;46(9):179-83.
    PMID: 12448467
    Environmental monitoring was carried out at Upper Layang Reservoir situated in Masai, Johor, Malaysia. The study shows that thermal stratification and natural mixing of the water column do exist in the reservoir and the level of stratification varies at different times of the year. Artificial destratification via diffused air aeration techniques was employed at the reservoir for two months. The results show that thermal stratification was eliminated after a week of continuous aeration. The concentrations of iron and to a lesser extent manganese in the water column was also reduced during the aeration period.
  5. Ismail R, Allaudin ZN, Lila MA
    Vaccine, 2012 Sep 7;30(41):5914-20.
    PMID: 22406276 DOI: 10.1016/j.vaccine.2012.02.061
    Gene therapy and vaccines are rapidly developing field in which recombinant nucleic acids are introduced in mammalian cells for enhancement, restoration, initiation or silencing biochemical function. Beside simplicity in manipulation and rapid manufacture process, plasmid DNA-based vaccines have inherent features that make them promising vaccine candidates in a variety of diseases. This present review focuses on the safety concern of the genetic elements of plasmid such as propagation and expression units as well as their host genome for the production of recombinant plasmid DNA. The highlighted issues will be beneficial in characterizing and manufacturing plasmid DNA for save clinical use. Manipulation of regulatory units of plasmid will have impact towards addressing the safety concerns raised in human vaccine applications. The gene revolution with plasmid DNA by alteration of their plasmid and production host genetics will be promising for safe delivery and obtaining efficient outcomes.
  6. Zahari Z, Inrahim MA, Tan SC, Mohamad N, Ismail R
    Turk J Med Sci, 2016 Dec 20;46(6):1743-1748.
    PMID: 28081321 DOI: 10.3906/sag-1507-132
    BACKGROUND/AIM: Sleep disturbances may contribute to poor treatment outcomes in opioid-dependent patients. The extent to which the sleep profiles of opioid-dependent patients differ from those of the general Malaysian population is not documented. This study compared opioid-naive subjects and opioid-dependent patients on methadone maintenance therapy (MMT) in terms of their sleep quality.

    MATERIALS AND METHODS: Participants comprised Malay male opioid-naive subjects (n = 159) and opioid-dependent patients (n = 160) from MMT clinics in Kelantan, Malaysia, between March and October 2013. Sleep quality was evaluated using the translated and validated Malay version of the Pittsburgh Sleep Quality Index (PSQI).

    RESULTS: The opioid-dependent patients exhibited higher global PSQI scores [adjusted mean (95% CI) = 5.46 (5.02, 5.90)] than the opioid-naive group [4.71 (4.26, 5.15)] [F (1, 313) = 4.77, P = 0.030].

    CONCLUSION: This study confirmed the poorer sleep quality among opioid-dependent patients on MMT, as manifested by their higher global PSQI scores. The sleep complaints in this patient population are a factor to consider and, when necessary, sleep evaluation and treatment should be undertaken to improve MMT patients' quality of sleep and overall treatment outcome.

  7. Goh SH, Khor KH, Ismail R, Megat Abdul Rani PA, Mohd Mohidin TB, Bahaman AR, et al.
    Trop Biomed, 2020 Dec 01;37(4):1074-1082.
    PMID: 33612759 DOI: 10.47665/tb.37.4.1074
    The incidence of leptospirosis seems to be on the rise and could be an alarming indirect indication of a global re-emergence. It is a potential public health threat when dogs are speculated to be involved in the transmission of leptospirosis through possible subclinical harbouring of Leptospira spp. and subsequent shedding into the environment. This study aimed to detect anti-leptospiral antibodies among dogs and their handlers using the microscopic agglutination test (MAT). Blood samples from 266 apparently healthy dogs and 194 dog handlers were collected at four working dog organisations and four dog shelters. Serum samples were tested using MAT against 20 leptospiral serovars with a cut-off titre >=1:100 (dog) and >=1:50 (dog handlers). Seventy dogs (70/266; 26.3%) were seropositive mainly against serovars Icterohaemorrhagiae, Ballum, Bataviae and Javanica (titres ranged: 1:100-1:800). Sixty-seven dog handlers (67/194; 34.5%) were seropositive mainly against serovars Grippotyphosa, Icterohaemorrhagiae and Malaysia (titres ranged: 1:50-1:200). Dogs were seropositive due to exposure, vaccination or active infection. Seropositive dog handlers could indicate exposure or active infection. This shows the potential of dogs in maintaining and spreading the infection in Malaysia. Due to the occupational risk as a result of frequent contact with dogs and exposure to contaminated environments, dog handlers should be made aware of the presence of this zoonotic disease.
  8. Lau WP, Ng KP, Ganapathy SS, Tah PC, Ismail R, Jalalonmuhali M, et al.
    Transplant Proc, 2022 Feb 03.
    PMID: 35125235 DOI: 10.1016/j.transproceed.2021.12.019
    BACKGROUND: Proteinuria and metabolic acidosis adversely affect long term renal allograft outcome and are highly prevalent in reported studies. The role of dietary intake in influencing proteinuria and metabolic acidosis remained uncertain. This study aims to determine the prevalence rate of proteinuria and metabolic acidosis among kidney transplant recipients (KTRs) and to study their relationship with dietary intake.

    METHODS: We performed a cross-sectional study on KTRs with functioning renal allograft and at least 3 months post transplant. Dietary protein, salt, and dietary acid load were estimated using 24-hour urine collection. Demographic characteristics, concomitant medications, medical history, and laboratory results were obtained from electronic medical records.

    RESULTS: A total of 204 KTRs were recruited with median age of 48 years (interquartile range [IQR], 18 years); male to female ratio was 61:39. A total of 79.9% (n = 163) were living related kidney transplants. The median duration after transplant was 71 months (IQR, 131 months), and median eGFR was 65 mL/min/1.73 m2 (IQR, 25 mL/min/1.73 m2). The prevalence rates of proteinuria (defined as ≥ 0.5 g/d) and metabolic acidosis (defined as at least 2 readings of serum bicarbonate ≤ 22 mmol/L in the past 6 months) were 17.7 % and 6.2%, respectively. High dietary protein of > 1.2 g/kg ideal body weight (adjusted odds ratio, 3.13; 95% CI, 1.35-7.28; P = .008) was significantly associated with proteinuria. Dietary protein, salt, and acid load did not correlate with chronic metabolic acidosis.

    CONCLUSIONS: The prevalence rate of proteinuria is consistent with published literature, but metabolic acidosis rate is extremely low in our cohort. High protein intake (> 1.2 g/kg ideal body weight) is a risk factor of proteinuria and may have negative impact on KTR outcome.

  9. Dom NC, Ahmad AH, Latif ZA, Ismail R
    Trans R Soc Trop Med Hyg, 2013 Nov;107(11):715-22.
    PMID: 24062522 DOI: 10.1093/trstmh/trt073
    Dengue has emerged as one of the major public health problems in Malaysia. The Ministry of Health, Malaysia, is committed in monitoring and controlling this disease for many years. The objective of this study is to analyze the dengue outbreak pattern on a monthly basis in Subang Jaya in terms of their spatial dissemination and hotspot identification.
  10. Che Dom N, Faiz Madzlan M, Nadira Yusoff SN, Hassan Ahmad A, Ismail R, Nazrina Camalxaman S
    Trans R Soc Trop Med Hyg, 2016 Apr;110(4):237-45.
    PMID: 27076510 DOI: 10.1093/trstmh/trw015
    Dengue fever (DF) is an urban vector-borne disease transmitted by Aedes aegypti and Aedes albopictus. Both species deposit their eggs in favorable breeding sites either in natural or artificial containers. An understanding of their habitat characteristics is crucial in curbing DF outbreaks
  11. Pan Y, Abd-Rashid BA, Ismail Z, Ismail R, Mak JW, Ong CE
    Protein J, 2011 Dec;30(8):581-91.
    PMID: 22001938 DOI: 10.1007/s10930-011-9365-6
    This study aimed to express two major drug-metabolizing human hepatic cytochromes P450 (CYPs), CYP2D6 and CYP3A4, together with NADPH-cytochrome P450 oxidoreductase (OxR) in Escherichia coli and to evaluate their catalytic activities. Full length cDNA clones of both isoforms in which the N-terminus was modified to incorporate bovine CYP17α sequence were inserted into a pCWori(+) vector. The modified CYP cDNAs were subsequently expressed individually, each together with OxR by means of separate, compatible plasmids with different antibiotic selection markers. The expressed proteins were evaluated by immunoblotting and reduced CO difference spectral scanning. Enzyme activities were examined using high performance liquid chromatography (HPLC) assays with probe substrates dextromethorphan and testosterone for CYP2D6 and CYP3A4, respectively. Results from immunoblotting demonstrated the presence of both CYP proteins in bacterial membranes and reduced CO difference spectra of the cell preparations exhibited the characteristic absorbance peak at 450 nm. Co-expressed OxR also demonstrated an activity level comparable to literature values. Kinetic parameters, K(m) and V(max) values determined from the HPLC assays also agreed well with literature values. As a conclusion, the procedures described in this study provide a relatively convenient and reliable means of producing catalytically active CYP isoforms suitable for drug metabolism and interaction studies.
  12. Miller V, Jenkins DA, Dehghan M, Srichaikul K, Rangarajan S, Mente A, et al.
    PMID: 38588684 DOI: 10.1016/S2213-8587(24)00069-X
    BACKGROUND: The association between the glycaemic index and the glycaemic load with type 2 diabetes incidence is controversial. We aimed to evaluate this association in an international cohort with diverse glycaemic index and glycaemic load diets.

    METHODS: The PURE study is a prospective cohort study of 127 594 adults aged 35-70 years from 20 high-income, middle-income, and low-income countries. Diet was assessed at baseline using country-specific validated food frequency questionnaires. The glycaemic index and the glycaemic load were estimated on the basis of the intake of seven categories of carbohydrate-containing foods. Participants were categorised into quintiles of glycaemic index and glycaemic load. The primary outcome was incident type 2 diabetes. Multivariable Cox Frailty models with random intercepts for study centre were used to calculate hazard ratios (HRs).

    FINDINGS: During a median follow-up of 11·8 years (IQR 9·0-13·0), 7326 (5·7%) incident cases of type 2 diabetes occurred. In multivariable adjusted analyses, a diet with a higher glycaemic index was significantly associated with a higher risk of diabetes (quintile 5 vs quintile 1; HR 1·15 [95% CI 1·03-1·29]). Participants in the highest quintile of the glycaemic load had a higher risk of incident type 2 diabetes compared with those in the lowest quintile (HR 1·21, 95% CI 1·06-1·37). The glycaemic index was more strongly associated with diabetes among individuals with a higher BMI (quintile 5 vs quintile 1; HR 1·23 [95% CI 1·08-1·41]) than those with a lower BMI (quintile 5 vs quintile 1; 1·10 [0·87-1·39]; p interaction=0·030).

    INTERPRETATION: Diets with a high glycaemic index and a high glycaemic load were associated with a higher risk of incident type 2 diabetes in a multinational cohort spanning five continents. Our findings suggest that consuming low glycaemic index and low glycaemic load diets might prevent the development of type 2 diabetes.

    FUNDING: Full funding sources are listed at the end of the Article.

  13. Lye JX, Kow RY, Ismail R, Khalid KA
    J Hand Surg Asian Pac Vol, 2021 Jun;26(2):166-179.
    PMID: 33928864 DOI: 10.1142/S2424835521500156
    Background: The Michigan Hand Outcomes Questionnaire (MHQ), a self-reported questionnaire for patients with hand disorders, has been widely used globally. It has been cross-culturally adapted into different languages across all continents. Aims of this study were to translate the MHQ into Malay language and to evaluate its reliability and validity compared with Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire in a Malay-speaking population. Methods: The MHQ was cross-culturally adapted into a Malay version based on the guidelines. A pre-testing involving thirty patients with hand disorders was performed to assess whether it was comprehensible to the target population. One hundred patients with hand disorders were recruited in this study to answer the MHQ and DASH questionnaires. The MHQ was tested twice with an interval of two weeks in between. Statistical analysis was performed to assess the reproducibility and internal consistency via the test-retest method and Cronbach's alpha calculation, respectively. The association between MHQ and DASH questionnaire was assessed with Spearman's correlation calculation. Results: In the pre-testing, twenty-six patients (86.7%) understood all the questions in the Malay version of MHQ. The test-retest analysis showed a good reliability across the duration of two weeks with the intraclass correlation coefficient of all subscales ranging from 0.925 to 0.984. Cronbach's alpha values of the Malay version MHQ ranged from 0.82 to 0.97, indicating a good internal consistency. Spearman's correlation factor of the MHQ in comparison with DASH showed a fair to moderately strong correlation with the values ranging from 0.513 to 0.757. Conclusions: The Malay version of MHQ was successfully translated and culturally-adapted with excellent reliability (reproducibility and internal consistency) and good construct validity.
  14. Isahak I, Mahayiddin AA, Ismail R
    PMID: 18041300
    The aims of the study were to determine the attack rate of influenza-like illness among inhabitants of five old folk homes nationwide using influenza vaccine as a probe and the effectiveness of influenza vaccination in prevention of influenza-like illness. We conducted a nonrandomized, single-blind placebo control study from June 2003 to February 2004. VAXIGRIP(R) 2003 Southern hemisphere formulation was used. Among 527 subjects, the attack rates of influenza-like illness in the influenza vaccine group were 6.4, 4.6 and 2.4% during the first, second and third 2-month periods, respectively. The attack rates of influenza-like illness in the placebo group were 17.7, 13.8 and 10.1%. Influenza vaccination reduced the risk of contracting influenza-like illness by between 14, and 45%. The vaccine effectiveness in reducing the occurrence of influenza-like illness ranged from 55 to 76%, during the 6-month study followup. The presence of cerebrovascular diseases significantly increased the risk of influenza-like illness (p < 0.005). Vaccine recipients had fewer episodes of fever, cough, muscle aches, runny nose (p < 0.001) and experience fewer sick days due to respiratory illness. Subjects who received influenza vaccination had clinically and statistically significant reductions in the attack rate of influenza-like illness. Our data support influenza vaccination of persons with chronic diseases and >50 year olds living in institutions.
  15. Wong JS, Bau R, Ahmad F, Ismail R, Yip AFY
    Med J Malaysia, 2013 Apr;68(2):141-3.
    PMID: 23629560 MyJurnal
    Atrial fibrillation (AF) is usually asymptomatic and often associated with established cardiovascular risk factors such as hypertension. The prevalence atrial fibrillation in patients admitted to Malaysian hospitals has been determined, but asymptomatic atrial fibrillation (AAF) in hypertensive patients in the primary care setting is not established. This study reports the prevalence of AAF in hypertensive patients in Malaysia, in a primary care setting. The overall prevalence of AAF was 0.75% with no differences between the gender. The prevalence of AAF increases with age - in the age groups of 30-39, >40-49, >50-59, >60-69, 70-79 and >80 years old were 0%, 0.17%, 0.35%, 2.32%, 2.59%, and 0% respectively. Hypertensive patients with age of ≥ 61 year old were associated with a probability of 10.6 times higher for AAF. We suggest the age threshold to screen for AAF to be age of 60. It is estimated that there are 49,029 Malaysians with AAF in 2010. A large population is at risk of AAF-related complications. There is justification for an even greater emphasis on diagnostic, primary and secondary prevention strategies.
    Study site: Klinik Kesihatan Bintulu, Sarawak, Malaysia
  16. Ong CE, Teh LK, Ismail R
    Med J Malaysia, 2002 Jun;57(2):251-60.
    PMID: 24326665
    Drug interactions can cause iatrogenic disease. If concurrent medications are taken, the potential exists for a drug interaction to occur. Renewed interest in the topic interactions has been generated by the fatal interactions involving non-sedating histamine H-1 antagonists and the recent intriduction of two therapeutic agents, the selective serotonin reuptake inhibitors (SSRIs) and HIV protease inhibitors, for the treatment of depression and AIDS, respectively. These three therapeutic agents have been implicated in clinically significant drug interactions. The consequences of these interactions vary in clinical significance, extent, and effect. Some interactions are theoretical whereas others may lead to severe iatrogenic adverse experiences including lethal consequences.The purpose of this review is to alert the medical practioner to potential drug interactions that may occur when these drugs are prescribed to patients. The pharmacological basis and clinical signficance of these interactions are reviewed. The pharmacological mechanisms underlying these interactions are illustrative of those that may be involved for many other medications. Doctors should be aware of the potential pitfall that may occur when certain groups of drugs are prescribed with concurrent medications.
  17. Ho JJ, Amar HSS, Ismail R
    Med J Malaysia, 2001 Sep;56(3):331-5.
    PMID: 11732079
    The Griffiths Scales for Mental Development were used to assess a group of 60 normal 2-year old Malaysian children (25 Indian, 23 Malay and 12 Chinese). The mean GQ was 104.2 (SD 9.3). This was significantly higher than the test mean of 100, p < 0.001. The mean score for Malaysian children was significantly higher on the locomotor, personal social, performance and practical reasoning subscales while they were significantly lower on the hand eye subscale and did not differ from the test mean on the hearing and speech subscale. There was a significant correlation between GQ and social class, r = -0.39, p < 0.05. Scores were lower than those currently obtained on British children, p < 0.001. Minor difficulties due to language and cultural factors arose over the interpretation of several items but with standardisation of these items the test is useful in Malaysian children.
  18. Ismail R, Doi S, Naganathna N
    Med J Malaysia, 1995 Dec;50(4):298-301.
    PMID: 8668046
    The spread of HIV infection into Malaysia is estimated to have occurred in the early 1980's. The first case of AIDS was reported here in 1986. As of March 31, 1994, the numbers have increased to 8049 HIV positive individuals detected in the country. The risk behaviours among those tested positive were intravenous drug use in 77.2%, sexual transmission in 4.5%, while the remainder are still under investigation. Pediatric AIDS constitutes 0.2% of positives. The high prevalence among intravenous drug users (IVDU) is likely to be due to mandatory testing for HIV upon entry to rehabilitation centres. The trend of HIV infection in this country seems to be highest amongst the intravenous drug users. The increasing number of HIV infected prostitutes and heterosexuals in our population is worrying. Since 1986, a total of 104 HIV positive individuals have been treated at the University Hospital, Kuala Lumpur, Malaysia. Of these, 25 have died and of those still alive, 5 have symptomatic disease. The most common AIDS-defining illness is Pneumocystis carinii pneumonia. Education programmes have been developed targeting the various high risk groups and the general population.
  19. Ismail R
    Med J Malaysia, 1987 Jun;42(2):124-6.
    PMID: 2971861
    Acne is one of the most common disorders affecting mankind. Although acne does not cause death, it however produces a lot of discomfort, disfigurement and psychological trauma, particularly in teenagers. Acne vulgaris is a chronic condition involving the pilosebaceous unit of the skin. It is characterised by the presence of comedones, inflammatory papules, pustules or cysts, and eventually by scarring. The end result of acne varies from hyperpigmentation, slight pitting, to extremely disfiguring scars that may develop into keloids. Acne fulminans is a rare disorder and is characterised by sudden explosive appearance of highly inflammatory, tender, crusted, ulcerated lesions involving the back, chest and face. It is one of the most scarring acute dermatologic disorders of young people. A case of acne fulminans in a young female who developed haemolysis due to dapsone is reported here.
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