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Mercury determination in hair of Malaysian fishermen by neutron activation analysis

Sarmani SB, Kiprawi AZ, Ismail RB

Biol Trace Elem Res, 1994;43-45:435-41.
PMID: 7710858

Fish has been known as a source of nonoccupational mercury exposure to fish-consuming population groups. In this study, hair samples collected from fishermen and their families residing in an industrialized area in Penang and a nonindustrialized area in Terengganu were analyzed for mercury by neutron activation. The range, arithmetic mean, geometric mean, and median of the mercury concentrations for the groups in Penang and in Terengganu were 0.45-16.68, 3.61, 3.49, and 2.96 and 6.79-18.31, 12.08, 11.69, and 12.05 mg/kg, respectively. Somewhat lower values than from the Penang group were found in a group from Selangor consisting mainly of office workers. The group in Penang took about 40-100 g of fish/d, whereas the group in Terengganu consumed twice as much. This shows that hair mercury levels depend on a fish consumption pattern, and not on the location of the population. The levels of mercury found in this study were similar to those reported by other workers for fish-consuming population groups worldwide.
Chloramphenicol in children: dose, plasma levels and clinical effects

Ismail R, Teh LK, Choo EK

Ann Trop Paediatr, 1998 Jun;18(2):123-8.
PMID: 9924573

Despite concerns about adverse effects, chloramphenicol (CMC) continues to be used in certain situations and, due to its low therapeutic index and variable pharmacokinetics, therapeutic drug monitoring (TDM) is often recommended. At our centre, CMC finds applications in typhoid and meningitis and TDM is routinely performed. Elsewhere in Malaysia, however, CMC is used without TDM. We therefore decided to evaluate our TDM for CMC in relation to its roles in CMC therapy in children, who constitute most of our patients. Our objective was also to develop strategies to improve our TDM for CMC use. Data were collected from 168 children given CMC for various indications and monitored by the TDM service. Plasma CMC was determined by HPLC and used to adjust doses to maintain concentrations within a range of 10-25 micrograms/ml. Outcomes measured included daily temperatures and haematological indices. Daily doses and plasma CMC varied greatly. Doses averaged 40.5 mg/kg for neonates and 75.5 for older children. Average peak concentrations were therapeutic in 60% and trough in 42%. Average duration of fever was 6.3 days and it was unaffected by plasma CMC. Typhoid was eradicated in 97% but nine children with other diagnoses died. Side-effects were confined to mild reversible haematological abnormalities which developed in 11% of children at plasma concentrations which tended to be high. We conclude that CMC remains useful in children with typhoid. Its use for other indications, however, should be reviewed. Routine TDM for CMC is probably not warranted, at least until a clearer role is defined by well designed prospective studies.
Therapeutic drug monitoring of gentamicin: a 6-year follow-up audit

Ismail R, Haq AH, Azman M, Rahman AF

J Clin Pharm Ther, 1997 Feb;22(1):21-5.
PMID: 9292398

In 1984 a therapeutic drug monitoring (TDM) service was established in Hospital Universiti Sains Malaysia (HUSM) and gentamicin concentrations were measured and used to design optimal regimens for the antibiotic. In this study we report on a 6-year follow-up audit since our first assessment of the service.
Gonococcal vulvovaginitis among female children in Malaysia

Ismail R, Toh CK, Ngeow YF

Sex Transm Dis, 1985 7 1;12(3):114-6.
PMID: 4035521

In this retrospective review of 16 children with vulvovaginitis due to Neisseria gonorrhoeae, the authors attempt to estimate the incidence of this infection and to ascertain the routes of transmission. From January 1977 to December 1982, 422 cases of gonococcal vulvovaginitis in women of all age groups were encountered at the University Hospital, Kuala Lumpur, Malaysia. Of these, 406 cases (96.2%) occurred in adults, and 16 cases (3.8%) occurred in children younger than 12 years of age. Penicillinase-producing N. gonorrhoeae (PPNG) strains were isolated from five (31%) of the 16 girls; all five cases were subsequently treated with cefuroxime and probenecid. The rest responded to intramuscular procaine penicillin. Although all patients appeared to be cured, only ten of 11 (two with PPNG) had test-of-cure cultures performed after treatment. Although interviewing the parents revealed no history of sexual contact in these children, nine of the girls were linked to culture-positive adult(s).
Fulltext 40 years of Alma Ata Malaysia: targeting equitable access through organisational and physical adaptations in the delivery of public sector primary care

Fadzil F, Jaafar S, Ismail R

Prim Health Care Res Dev, 2020 02 24;21:e4.
PMID: 32090729 DOI: 10.1017/S146342362000002X

This paper illustrates the development of Primary Health Care (PHC) public sector in Malaysia, through a series of health reforms in addressing equitable access. Malaysia was a signatory to the Alma Ata Declaration in 1978. The opportunity provided the impetus to expand the Rural Health Services of the 1960s, guided by the principles of PHC which attempts to address the urban-rural divide to improve equity and accessibility. The review was made through several collation of literature searches from published and unpublished research papers, the Ministry of Health annual reports, the 5-year Malaysia Plans, National Statistics Department, on health systems programme and infrastructure developments in Malaysia. The Public Primary Care Health System has evolved progressively through five phases of organisational reforms and physical restructuring. It responded to growing needs over a 40-year period since the Alma Ata Declaration in 1978, keeping equity, accessibility, efficiency and universal health coverage consistently in the backdrop. There were improvements of maternal, infant mortality rates as well as accessibility to health services for the population. The PHC Reforms in Malaysia are the result of structured and strategic investment. However, there will be continuing dilemma between cost-effectiveness and equity. Hence, continuous efforts are required to look at opportunity costs of alternative strategies to provide the best available solution given the available resources and capacities. While recognising that health systems development is complex with several layers and influencing factors, this paper focuses on a small but crucial aspect that occupies much time and energies of front-line managers in the health.
CYP2B6 and OPRM1 Receptor Polymorphisms at Methadone Clinics And Novel OPRM1 Haplotypes: A Cross-Sectional Study

AlMeman AA, Ismail R, Perola M

Drug Metab Lett, 2016;10(3):213-218.
PMID: 27515451

INTRODUCTION: Methadone is accepted as an alternative therapy in opioid use disorders worldwide. Methadone responsiveness, however, is affected by a range of CYP450 enzymes and OPRM1 polymorphisms.
OBJECTIVE: This study sought to detect CYP2B6 and OPRM1 variants and their genotypes, as major contributors to inter-variability in methadone responsiveness and methadone dose requirements.
METHODS: We carried out a prospective experimental one-phase pharmacogenetic study in four addiction clinics in Malaysia. Patients on stable methadone maintenance therapy were recruited. The prevalence of the CYP2B6 and OPRM1 polymorphisms was determined using a nested polymerase chain reaction (PCR), followed by genotyping. A two-step multiplex PCR method was developed to simultaneously detect the 26 SNPs in these two genes.
RESULTS: 120 males were recruited for this study. The patients were between 21and 59 years old, although the majority of the patients were in their 30s. C64T and G15631T in CYP2B6and G31A, G691C, and A118G in OPRM1 were found to be polymorphic, and the allelic frequencies of each were calculated. We further detected eight new haplotypes.
CONCLUSION: C64T and G15631T in CYP2B6and G31A, G691C, and A118G in OPRM1were found to be polymorphic. The new haplotypes may give a new insight on methadone clinics.
Fulltext Application of Fuzzy Delphi in the Selection of COPD Risk Factors among Steel Industry Workers

Dapari R, Ismail H, Ismail R, Ismail NH

Tanaffos, 2017;16(1):46-52.
PMID: 28638424

BACKGROUND: The Delphi method has been widely applied in many study areas to systematically gather experts' input on particular topic. Recently, it has become increasingly well known in health related research. This paper applied the Fuzzy Delphi method to enhance the validation of a questionnaire pertaining chronic obstructive pulmonary disease (COPD) risk factors among metal industry workers.

MATERIALS AND METHODS: A detailed, predefined list of possible risk factors for COPD among metal industry workers was created through a comprehensive and exhaustive review of literature from 1995 to 2015. The COPD questionnaire were distributed among people identified as occupational, environmental, and hygiene experts. Linguistic variable using Likert scale was used by the expert to indicate their expert judgment of each item. Subsequently, the linguistic variable was converted into a triangular fuzzy number. The average score of the fuzzy number will be used to determine whether the item will be removed or retained.

RESULTS: Ten experts were involved in evaluating 26 items. The experts were in agreement with most of the items, with an average fuzzy number range between 0.429 and 0.800. Two items were removed and three items were added, leaving a total 26 items selected for the COPD risk factors questionnaire. The experts were in disagreement with each other for items F10 and F11 where most of the experts claimed that the question is too subjective and based on self-perception only.

CONCLUSION: The fuzzy Delphi method enhanced the accuracy of the questionnaire pertaining to COPD risk factors, and decreased the length of the established tools.
Fulltext 40 years of Alma Ata Malaysia: Targeting equitable access through organisational and physical adaptations in the delivery of public sector primary care - CORRIGENDUM

Fadzil F, Jaafar S, Ismail R

Prim Health Care Res Dev, 2020 05 21;21:e13.
PMID: 32434613 DOI: 10.1017/S1463423620000146
Fulltext Neuropsychiatric Presentation in Indirect Carotid-Cavernous Fistula: A Case Report

Ying Sze C, Bakin S, Ismail R

Cureus, 2023 Apr;15(4):e37523.
PMID: 37193417 DOI: 10.7759/cureus.37523

Carotid-cavernous fistula (CCF) is a rare sight and potentially life-threatening disorder arising from an abnormal connection between the carotid artery and the cavernous sinus. It can be classified into direct or indirect according to different arteriovenous shunts. Direct CCF usually has dramatic ocular presentations, whereas indirect CCF has a more insidious course and may be associated with neurologic symptoms in posteriorly draining fistulas. A 61-year-old gentleman presented with five days history of altered behavior and double vision preceding a bulging left eye. Ocular examination showed left eye proptosis, generalized chemosis, total ophthalmoplegia, and raised intra-ocular pressure. Computed tomography angiography (CTA) brain and orbit demonstrated dilated superior ophthalmic vein (SOV) with communication to a tortuous cavernous sinus suggestive of carotid-cavernous fistula (CCF). Digital subtraction angiography (DSA) eventually confirmed the presence of indirect communication between branches of the bilateral external carotid artery (ECA) and left cavernous sinus, which is a type C indirect CCF according to the Barrow classification. Total embolization of left CCF was successfully achieved via transvenous access. A marked reduction of proptosis and intra-ocular pressure was noted following the procedure. Although rare, neuropsychiatric presentation could be a possible presentation of CCF, and treating physicians should be aware of it. A high index of suspicion and prompt diagnosis is crucial in managing this sight and life-threatening condition. Early intervention can improve the prognosis of patients.
Nasal Irrigation as Treatment in Sinonasal Symptoms Relief: A Review of Its Efficacy and Clinical Applications

Abdullah B, Periasamy C, Ismail R

Indian J Otolaryngol Head Neck Surg, 2019 Nov;71(Suppl 3):1718-1726.
PMID: 31763232 DOI: 10.1007/s12070-017-1070-0

Nasal irrigations have been used for centuries without any scientific data to determine its efficacy. Despite their widespread use, much confusion exist about the mechanism of action, preparation, indications and therapeutic advantage of nasal irrigations. Anecdotal evidence and poorly controlled studies add to the confusion. Recent evidence provides strong scientific justification of the benefits and advantages of using nasal irrigations in sinonasal symptoms relief. The present review of the evidence based literature highlights its efficacy and clinical applications.
Fulltext Effect of Cymbopogon citratus and Citral on Vascular Smooth Muscle of the Isolated Thoracic Rat Aorta

Devi RC, Sim SM, Ismail R

Evid Based Complement Alternat Med, 2012;2012:539475.
PMID: 22675383 DOI: 10.1155/2012/539475

Cymbopogon citratus has been shown to have antioxidant, antimicrobial, antispasmodic and chemo-protective properties. Citral, is the major constituent of C. citratus. This study investigated the effects of methanolic extracts of leaves (LE), stems (SE), and roots (RE) of C. citratus and citral on vascular smooth muscle and explored their possible mechanisms of action. The experiment was conducted using isolated tissue preparations, where citral, LE, SE, and RE were added separately into a tissue bath that contained aortic rings, which were pre-contracted with phenylephrine (PE). Citral, LE, and RE exhibited a dose-dependent relaxant effect on the PE-induced contractions. Citral appeared to partially act via NO as its vasorelaxant effect was attenuated by L-NAME. However, the effect of LE may involve prostacyclin as indomethacin reversed the relaxant effect of LE on the PE-induced contraction. Furthermore, citral, LE, and RE abolished the restoration of PE-induced contraction caused by the addition of increasing doses of calcium in both endothelium intact and denuded rings. These findings suggest that the relaxation effect of citral, LE, and RE is endothelium-independent and may be mainly by affecting the intracellular concentration of calcium. Citral may partially act through the NO pathway while a vasodilator prostaglandin may mediate the effect of LE.
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.
Fulltext Graphene nanoribbon field-effect transistor at high bias

Ghadiry M, Ismail R, Saeidmanesh M, Khaledian M, Manaf AA

Nanoscale Res Lett, 2014;9(1):604.
PMID: 25404874 DOI: 10.1186/1556-276X-9-604

Combination of high-mean free path and scaling ability makes graphene nanoribbon (GNR) attractive for application of field-effect transistors and subject of intense research. Here, we study its behaviour at high bias near and after electrical breakdown. Theoretical modelling, Monte Carlo simulation, and experimental approaches are used to calculate net generation rate, ionization coefficient, current, and finally breakdown voltage (BV). It is seen that a typical GNR field-effect transistor's (GNRFET) breakdown voltage is in the range of 0.5 to 3 V for different channel lengths, and compared with silicon similar counterparts, it is less. Furthermore, the likely mechanism of breakdown is studied.
Measurement of dengue epidemic spreading pattern using density analysis method: retrospective spatial statistical study of dengue in Subang Jaya, Malaysia, 2006-2010

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.
Fulltext Prevalence of asymptomatic atrial fibrillation in Malaysian patients with hypertension

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
In vitro approaches to investigate cytochrome P450 activities: update on current status and their applicability

Ong CE, Pan Y, Mak JW, Ismail R

Expert Opin Drug Metab Toxicol, 2013 Sep;9(9):1097-113.
PMID: 23682848 DOI: 10.1517/17425255.2013.800482

Cytochromes P450 (CYPs) play a central role in the Phase I metabolism of drugs and other xenobiotics. It is estimated that CYPs can metabolize up to two-thirds of drugs present in humans. Over the past two decades, there have been numerous advances in in vitro methodologies to characterize drug metabolism and interaction involving CYPs.
Lupus vulgaris in an immunocompromised patient

Jalalonmuhali M, Lee YY, Lee CK, Ismail R, Chandran PA

Int J Dermatol, 2014 Feb;53(2):234-7.
PMID: 22913324 DOI: 10.1111/j.1365-4632.2012.05463.x
In vitro modulatory effects of flavonoids on human cytochrome P450 2C8 (CYP2C8)

Pang CY, Mak JW, Ismail R, Ong CE

Naunyn Schmiedebergs Arch Pharmacol, 2012 May;385(5):495-502.
PMID: 22307090 DOI: 10.1007/s00210-012-0731-5

The inhibitory effects of five flavonoids with distinct chemical classes (flavones [luteolin], flavonols [quercetin and quercitrin], and flavanones [hesperetin and hespiridin]) on cDNA-expressed CYP2C8 were investigated. CYP2C8 was co-expressed with NADPH-cytochrome P450 reductase in Escherichia coli and used to characterise potency and mechanism of these flavonoids on the isoform. Tolbutamide 4-methylhydroxylase, a high-performance liquid chromatography-based assay, was selected as marker activity for CYP2C8. Our results indicated that the flavonoids inhibited CYP2C8 with different potency. The order of inhibitory activities was quercetin > luteolin > hesperetin > hesperidin > quercitrin. All of these compounds however exhibited mechanism-based inhibition. A number of structural factors were found to be important for inhibition; these include the molecular shape (volume to surface ratio), the number of hydroxyl groups as well as glycosylation of the hydroxyl group. Quercetin was the most potent inhibitor among the flavonoids examined in this study, and our data suggest that it should be examined for potential pharmacokinetic drug interactions pertaining to CYP2C8 substrates in vivo.
Developmental haemostasis for factor V and factor VIII levels in neonates: a case report of spontaneous cephalhaematoma

Abdullah WZ, Ismail R, Nasir A, Mohamad N, Hassan R

Fetal Pediatr Pathol, 2013 Apr;32(2):77-81.
PMID: 22536947 DOI: 10.3109/15513815.2012.671447

Combined factor V and VIII deficiency is a rare bleeding disorder. Diagnosis of congenital coagulation factor deficiency in a neonate is challenging due to "immaturity" of the hemostatic system. A 2-day-old baby girl presented with spontaneous cephalhematoma. She was found to have persistent abnormal coagulation tests and finally diagnosed as combined factor V and VIII deficiency. Interestingly, factor V and factor VIII in developmental hemostasis are quite similar with adult levels in newborn, and hence early diagnosis is possible. An investigation to detect underlying hemostatic defects is recommended in newborns with spontaneous cephalhematoma.
Fulltext Bullous pemphigoid in an elderly patient with myelodysplastic syndrome and refractory anemia coupled with excess of blast

Lee YY, Bee PC, Lee CK, Naiker M, Ismail R

Ann Dermatol, 2011 Dec;23(Suppl 3):S390-2.
PMID: 22346286 DOI: 10.5021/ad.2011.23.S3.S390

Bullous pemphigoid (BP) has a recognized association with solid organ tumors, but is relatively rare in hematological malignancies. We report a 67-year-old male who developed BP after being diagnosed with myelodysplastic syndrome and refractory anemia with excess of blast (RAEB). Skin biopsy elucidated sub-epidermal bulla using direct immunofluorescence, revealing linear C3 and IgG deposits along the basement membrane. His BP was recalcitrant to the conventional treatment and only responded to a combination of high dose oral prednisolone and azathioprine. The relative refractory nature of his condition and concurrent RAEB supports a paraneoplastic nature.

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