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Validation of a high-performance liquid chromatography method for tramadol and o-desmethyltramadol in human plasma using solid-phase extraction

Gan SH, Ismail R

J Chromatogr B Biomed Sci Appl, 2001 Aug 15;759(2):325-35.
PMID: 11499486

An HPLC system using solid-phase extraction and HPLC with UV detection has been validated in order to determine tramadol and o-desmethyltramadol (M1) concentrations in human plasma. The method developed was selective and linear for concentrations ranging from 50 to 3,500 ng/ml (tramadol) and 50 to 500 ng/ml (M1) with mean recoveries of 94.36 +/- 12.53% and 93.52 +/- 7.88%, respectively. Limit of quantitation (LOQ) was 50 ng/ml. For tramadol, the intra-day accuracy ranged from 95.48 to 114.64% and the inter-day accuracy, 97.21 to 103.24%. Good precision (0.51 and 18.32% for intra- and inter-day, respectively) was obtained at LOQ. The system has been applied to determine tramadol concentrations in human plasma samples for a pharmacokinetic study.
Fulltext The prevalence of Actinobacillus actinomycetemcomitans in a healthy Malay population in Malaysia

Zahari, N.M., Ismail, R., Bunyarit, S.S., Shafiei, Z., Al Rawenduzy, K.C.M.A.

Malaysian Dental Journal, 2007;28(1):45-50.
MyJurnal

Actinobacillus actinomycetemcomitans is considered a major pathogen in periodontal disease. The aim of this study was to determine the prevalence of A. actinomycetemcomitans from 46 subjects aged 20-24 years old of who were all periodontally healthy Malays.
Fulltext Ambit determination method in estimating rice plant population density

Abu Bakar, B., Abdul Rahman, M.S., Teoh, C.C., Abdullah, M.Z.K., Ismail, R.

Food Research, 2018;2(2):177-182.
MyJurnal

Rice plant population density is a key indicator in determining the crop setting and fertilizer application rate. It is therefore essential that the population density is monitored to ensure that a correct crop management decision is taken. The conventional method of determining plant population is by manually counting the total number of rice plant tillers in a 25 cm x 25 cm square frame. Sampling is done by randomly choosing several different locations within a plot to perform tiller counting. This sampling method is time consuming, labour intensive and costly. An alternative fast estimating method was developed to overcome this issue. The method relies on measuring the outer circumference
or ambit of the contained rice plants in a 25 cm x 25 cm square frame to determine the number of tillers within that square frame. Data samples of rice variety MR219 were collected from rice plots in the Muda granary area, Sungai Limau Dalam, Kedah. The data were taken at 50 days and 70 days after seeding (DAS). A total of 100 data samples were collected for each sampling day. A good correlation was obtained for the variety of 50 DAS and 70 DAS. The model was then verified by taking 100 samples with the latching strap for 50 DAS and 70 DAS. As a result, this technique can be used as a fast, economical and practical alternative to manual tiller counting. The technique can potentially be used in the development of an electronic sensing system to estimate paddy plant population density.
Genetic polymorphism of CYP2D6: Malaysian Indians have the highest frequency for CYP2D6*4 in Asia

Ismail R, Teh LK

Eur J Clin Pharmacol, 2001 Oct;57(8):617-8.
PMID: 11758642
Malignant melanoma in Malaysia--a report of 23 cases

Ismail R, Meng LL

J Dermatol, 1988 Apr;15(2):168-71.
PMID: 3049733
Fulltext Utility of Lung Perfusion SPECT/CT in Detection of Pulmonary Thromboembolic Disease: Outcome Analysis

Tan TH, Ismail R

Nucl Med Mol Imaging, 2023 Feb;57(1):1-8.
PMID: 35013684 DOI: 10.1007/s13139-021-00726-2

PURPOSE: To evaluate the clinical outcome of Q-SPECT/CT in pulmonary thromboembolic disease.
METHODS: From Jan 2020 to Jan 2021, 30 consecutive patients (M:F = 8:22; median age = 52 year (21-89)) suspected of having acute pulmonary embolism (PE) or chronic thromboembolic pulmonary hypertension (CTEPH) were referred for non-contrasted Q-SPECT/CT. All patients were COVID-19 PCR negative. MSKCC Q-SPECT/CT and/or PISAPED criteria were used to determine the presence of thromboembolic disease in Q-SPECT/CT. Final diagnosis was made based on composite reference standards that included at least 2-month clinical cardiorespiratory assessment and follow-up imaging.
RESULTS: Q-SPECT/CT was positive in 19 patients: indeterminate in 1 and 10 were negative. Three false positive cases were observed during follow-up. Of the remaining 16 true positives, all patients' cardiorespiratory symptom were improved or stabilised after treatment with anticoagulants. The overall sensitivity, specificity, PPV, NPV and accuracy of Q-SPECT/CT were 100% (95% CI, 79.41-100%), 78.57% (95% CI, 49.20-95.34%), 84.21% (95% CI, 66.41-93.57%), 100% and 90.00% (95% CI, 73.47-97.89%) respectively.
CONCLUSIONS: In the current COVID-19 pandemic, Q-SPECT/CT can be an alternative modality to detect pulmonary thromboembolic disease. Normal Q-SPECT/CT excludes pulmonary thromboembolic disease with high degree of certainty. However, false positive has been observed.
Fulltext Use of pilot plant scale continuous fryer to simulate industrial production of potato chips: thermal properties of palm olein blends under continuous frying conditions

Tarmizi AH, Ismail R

Food Sci Nutr, 2014 Jan;2(1):28-38.
PMID: 24804062 DOI: 10.1002/fsn3.76

Binary blends of palm olein (PO) with sunflower oil (SFO), canola oil (CNO), and cottonseed oil (CSO) were formulated to assess their stability under continuous frying conditions. The results were then compared with those obtained in PO. The oil blends studied were: (1) 60:40 for PO + SFO; (2) 70:30 for PO + CNO; and (3) 50:50 for PO + CSO. The PO and its blends were used to fry potato chips at 180°C for a total of 56 h of operation. The evolution of analytical parameters such as tocols, induction period, color, p-anisidine value, free fatty acid, smoke point, polar compounds, and polymer compounds were evaluated over the frying time. Blending PO with unsaturated oils was generally proved to keep most qualitative parameters comparable to those demonstrated in PO. Indeed, none of the oils surpassed the legislative limits for used frying. Overall, it was noted that oil containing PO and SFO showed higher resistance toward oxidative and hydrolytic behaviors as compared to the other oil blends.
Pharmacokinetics of phenytoin in routine clinic patients in Malaysia

Ismail R, Rahman AF, Chand P

J Clin Pharm Ther, 1994 Aug;19(4):245-8.
PMID: 7989403

We estimated individual and population Michaelis-Menten pharmacokinetic parameters for phenytoin (DPH) in epileptic patients attending our neurology clinic using the computer programme. OPT. Our results agreed well with literature values but were lower than those we obtained earlier in a smaller number of patients. The Km was independent of age, weight and sex but there was a weak, correlation between Vm and body weight. We conclude that the use of population Vm and Km in normograms could lead to errors in DPH dose estimations as they correlated very poorly with patient characteristics. OPT was easy to use and sufficiently accurate for deriving dose estimates in routine patients. Its use would enable practitioners to generate their patients' own parameters for use in individual dosage adjustments. The estimates can subsequently be updated as more data become available.
Fulltext Therapeutic drug monitoring for gentamicin in Hospital Universiti Sains Malaysia

Ismail R, Sarriff A, Abdul Rahman AF

Med J Malaysia, 1990 Mar;45(1):57-64.
PMID: 2152070

We evaluated the usefulness of therapeutic drug monitoring (TDM) for gentamicin and the use of a two-point peak and trough pair concentration method to adjust its dose. Of the 194 patients included, initial concentrations were appropriate in only sixty nine. In the seventy one cases of dosage adjustments using this method, those attaining therapeutic levels increased overall from 38% to 67%. It is concluded that TDM for gentamicin with dosage adjustment using this simple pharmacokinetic approach is useful and adequate in monitoring for gentamicin therapy.
Fulltext Radiation-induced formation of acrylated palm oil nanoparticle using pluronic f-127 microemulsion system

Tajau, R., Wan Yunus, W.M.Z., Mohd Dahlan, K.Z., Mahmood, M.H., Hashim, K., Ismail, M., et al.

Pertanika Journal of Science & Technology, 2013;21(1):127-134.
MyJurnal

This study demonstrated the utilization of radiation-induced initiator methods for the formation of
nanoparticles of Acrylated Palm Oil (APO) using aqueous Pluronic F-127 (PF-127) microemulsion
system. This microemulsion system was subjected to gamma irradiation to form the crosslinked APO
nanoparticles. Dynamic light scattering (DLS), Fourier Transform Infrared (FTIR) spectroscopy and
Transmission Electron Microscopy (TEM) were used to characterize the size and the chemical structure
of the nanoparticles. As a result, the size of the APO nanoparticle was decreased when the irradiation
dose increased. The decrease in size might be due to the effects of intermolecular crosslinking and
intramolecular crosslinking reactions of the APO nanoparticles during irradiation process. The size of the
nanoparticle is in the range of 98 to 200 nanometer (nm) after irradiation using gamma irradiator. This radiation-induced method provides a free initiator
induced and easy to control process as compared
to the classical or chemical initiator process. The
study has shown that radiation-induced initiator
methods, namely, polymerization and crosslinking
in the microemulsion, were promising for the
synthesis of nanoparticles.
Fulltext Statistical methods used to test for agreement of medical instruments measuring continuous variables in method comparison studies: a systematic review

Zaki R, Bulgiba A, Ismail R, Ismail NA

PLoS One, 2012;7(5):e37908.
PMID: 22662248 DOI: 10.1371/journal.pone.0037908

Accurate values are a must in medicine. An important parameter in determining the quality of a medical instrument is agreement with a gold standard. Various statistical methods have been used to test for agreement. Some of these methods have been shown to be inappropriate. This can result in misleading conclusions about the validity of an instrument. The Bland-Altman method is the most popular method judging by the many citations of the article proposing this method. However, the number of citations does not necessarily mean that this method has been applied in agreement research. No previous study has been conducted to look into this. This is the first systematic review to identify statistical methods used to test for agreement of medical instruments. The proportion of various statistical methods found in this review will also reflect the proportion of medical instruments that have been validated using those particular methods in current clinical practice.
Fulltext Scaling-up recombinant plasmid DNA for clinical trial: current concern, solution and status

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.
Spasmolytic effect of citral and extracts of Cymbopogon citratus on isolated rabbit ileum

Devi RC, Sim SM, Ismail R

J Smooth Muscle Res, 2011;47(5):143-56.
PMID: 22104376

Cymbopogon citratus, commonly known as lemongrass, has been shown to have antioxidant, antimicrobial and chemo-protective properties. Citral, a monoterpenoid, is the major constituent of C. citratus that gives off a lemony scent and is postulated to be responsible for most of its actions. In addition, C. citratus has been traditionally used to treat gastrointestinal discomforts, however, the scientific evidence for this is still lacking. Thus, the aim of the present study was to investigate the effect of the extracts of various parts of C. citratus (leaves, stems and roots) and citral on the visceral smooth muscle activity of rabbit ileum. The effect of the test substances were tested on the spontaneous contraction, acetylcholine (ACh)- and KCl-induced contractions. Citral at doses between 0.061 mM to 15.6 mM and the extract of leaves at doses between 0.001 mg/mL to 1 mg/mL significantly reduced the spontaneous, ACh- and KCl-induced ileal contractions. When the ileum was incubated in K(+)-rich-Ca(2+)-free Tyrode's solution, it showed only minute contractions. However, the strength of contraction was increased with the addition of increasing concentrations of CaCl(2). The presence of citral almost abolished the effect of adding CaCl(2), while the leaf extract shifted the calcium concentration-response curve to the right, suggesting a calcium antagonistic effect. These results were similar to that elicited by verapamil, a known calcium channel blocker. In addition, the spasmolytic effect of citral was observed to be reduced by the nitric oxide synthase inhibitor, L-NAME. In conclusion, citral and the leaf extract of C. citratus exhibited spasmolytic activity and it appeared that they may act as calcium antagonists. Furthermore, the relaxant effect of citral, but not that of the leaf extract may be mediated by nitric oxide suggesting the presence of other chemical components in the leaf extract other than citral.
Effectiveness of influenza vaccination in prevention of influenza-like illness among inhabitants of old folk homes

Isahak I, Mahayiddin AA, Ismail R

Southeast Asian J. Trop. Med. Public Health, 2007 Sep;38(5):841-8.
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.
Metastatic mucinous carcinoma of the eyelid

Kaur G, Ismail R, Harun H

Malays J Pathol, 2005 Dec;27(2):117-8.
PMID: 17191395

Metastatic eyelid tumours are rare and account for less than 2% of all eyelid neoplasms. We report a case of metastatic breast carcinoma to the eyelid in a 60-year-old Chinese lady presenting with a 2-year history of enlarging, painless nodular lower eyelid swelling. The 1 cm diameter lesion was provisionally diagnosed as a sebaceous cyst. However the excision biopsy revealed a mucinous carcinoma expressing oestrogen receptor protein. She had a past history of mastectomy one year previously and histology showed an infiltrating ductal carcinoma (oestrogen receptor status negative) without evidence of axillary lymph node metastasis. She had completed adjuvant radio- and chemotherapy. Further treatment of the current lesion involved a wide excision which did not show any residual malignancy. She had no other evidence of metastasis and was treated with letrozol. We highlight this case to create awareness among clinicians and opthalmologists on the possibility of metastatic disease as a cause of eyelid swelling, especially in patients with a history of cancer. It may also be the first sign of metastatic disease of an internal malignancy. A review of the literature is also presented.
Malaysian Indians are genetically similar to Caucasians: CYP2C9 polymorphism

Zainuddin Z, Teh LK, Suhaimi AW, Ismail R

J Clin Pharm Ther, 2006 Apr;31(2):187-91.
PMID: 16635054

CYP2C9 is one of the major drug metabolizing enzymes for many drugs including warfarin, NSAIDs and losartan. It is polymorphic in many populations. Data on the distribution of CYP2C9 and the implication of CYP2C9 polymorphism in the Malaysian population is lacking. Our objectives were therefore to investigate the prevalence of CYP2C9 variants among unrelated healthy volunteers of Malays, Chinese and Indians in Malaysia.
Fulltext Patient's knowledge and perception towards the use of non-steroidal anti-inflammatory drugs in rheumatology clinic northern Malaysia

Sulaiman W, Seung OP, Ismail R

Oman Med J, 2012 Nov;27(6):505-8.
PMID: 23226825 DOI: 10.5001/omj.2012.121

OBJECTIVE: In Rheumatology, non-steroidal anti-inflammatory drugs (NSAIDs) has been widely prescribed and used. However, despite their clinical benefits in the management of inflammatory and degenerative joint disease, NSAIDs have considerable side effects, mostly affecting the upper gastrointestinal system, which therefore, limit their use. This study was conducted to determine the patients' knowledge and perception regarding the used of NSAIDS.
METHODS: A total of 120 patients who attended the rheumatology clinic Hospital, Raja Permaisuri Bainun, Malaysia, and received NSAIDs more than 3 months were interviewed irrespective of their rheumatological conditions. Patient's knowledge and perception on the side effects of NSAIDs were recorded.
RESULT: Fifty-four percent of the patients obtained information regarding the side effect of NSAIDs either from the rheumatologist, rheumatology staff nurse or other medical staffs (75.4%). The remaining 45.8% were naive of such knowledge. Fifteen percent obtained the information by surfing the internet and 9.2% from printed media. Twenty-four (24.2%) patients, experienced indigestion and/or stomach discomfort attributed to NSAIDs used. Two patients (1.7%) had hematemesis and malena once.
CONCLUSION: This study shows that half of the patients who attended the rheumatology clinic were unaware of the side effect of NSAIDs. Available data showed that most of the knowledgeable patients are more conscience and self-educated. This study also reveals the important roles of clinicians, trained staff nurses as well as the pharmacist in providing the guidance and knowledge of any medication taken by patients.
KEYWORDS: Knowledge; NSAIDs; Rheumatology; Side effects

Study site: rheumatology clinic Hospital, Raja Permaisuri Bainun, Malaysia,
Fulltext Haplotypes frequencies of CYP2B6 in Malaysia

Musa N, Zulkafli MI, Talib N, Mohamad N, Fauzi H, Ismail R

J Postgrad Med, 2012 Oct-Dec;58(4):235-41.
PMID: 23298916 DOI: 10.4103/0022-3859.105439

Drugs with complex pharmacology are used in the management of drug use disorder (DUD) and HIV/AIDS in Malaysia and in parts of South-East Asia. Their multiethnic populations suggest complexity due to the genetic polymorphism, such as CYP2B6 that metabolizes methadone and anti-retroviral.
CYP2D6 phenotypes among Malays in Malaysia

Ismail R, Hussein A, Teh LK, Nizam Isa M

J Clin Pharm Ther, 2000 Oct;25(5):379-83.
PMID: 11123490

Although they originated from China, Malays have undergone a lot of intermarriages. A study suggested that CYP2D6 poor metabolism (PM) phenotype was more common in Malays compared to Chinese. CYP2D6 is highly polymorphic and is involved in the metabolism of many drugs and has been implicated in some environmentally-induced diseases. It is therefore useful to further study this polymorphism in Malays.
Fulltext Involvement of cytochromes p450 in drug-drug interactions: an overview

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.

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