Displaying publications 1 - 20 of 62 in total

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  1. Mak, Joon-Wah
    MyJurnal
    The research mentorship programme is unique in that it is a planned journey undertaken by the mentor and mentee, preferably with well-defined milestones along the journey. During the journey, familiar landmarks will be pointed out by the mentor. In path-finding situations the experience and wisdom of the mentor and the critical appraisal of both mentor and mentee will contribute to learning from the encounter. In most mentor-mentee partnerships, a formal acceptance to the relationship, well-defined landmarks measuring progress in the journey, regular appraisal of the skills developed and acquired, and phased, judicious modification in the individual roles of that relationship will be required. Although there is no consensus on the elements of mentorship, there are some strategies which can contribute to the success of the relationship. Critical success factors include convergence of the research area within the broad expertise of the research mentor. The research mentor should have a proven research track record and is committed to serve in that official capacity. The research mentoring process is dynamic and characteristics of both mentor and mentee contribute to the robustness of that relationship. The mentee would have identified some attributes of the mentor that are desirable and is willing to work hard to achieve, build on, and improve upon. In the research setting endpoint measurements of success will be based on recognition of the research standing of the mentee, measurable outcomes such as number of papers in top tier journals, citation indices, etc. consultancies attracted as well as invitations to deliver plenaries in scientific conferences, patents filed and research findings translated and applied, and other measures of research productivity. In the pursuit of research excellence the mentee would have imbibed values of professionalism and ethics in research and would have constantly kept in mind that to be successful, the mentee would be able to excel beyond his mentor and that the next generation of researchers will seek mentorship from him.
  2. Mak, Joon-Wah
    MyJurnal
    The International Medical University (IMU) has encouraged and facilitated research activities since 2001. Research activities by undergraduates, postgraduates, and faculty members have increased substantially since then. The governance aspects of research activities are closely monitored by the Institutional Review Board which is the IMU-Joint Committee on Research and Ethics. (Copied from article)
  3. Mak JW
    PMID: 7973952
    The lymphatic filarial parasites which affect about 90 million people worldwide have similar host-parasite relationships in man. They are all able to survive, reproduce and cause chronic infections if they can successfully evade the protective responses of the host. Studies to investigate the wide spectrum of clinical manifestations of the infection even among those living in similar endemic areas and with presumed equal exposure to infective larvae, have been hampered by the lack of animal models showing similar host-parasite responses. The recent use of the nude mouse infected with Brugia spp, and the leaf-monkey (Presbytis spp) infected with B. malayi or Wuchereria spp for the study of immune responses and the associated pathology of these infections, has elucidated some of the host protective immune responses as well as the associated immunopathological reactions. The successfully entrenched parasite elicits minimal reactions and pathology, but with the onset of effective host responses, whether assisted by chemotherapy, development of protective immunity or both, severe inflammatory responses may occur. The role of such immune mediated response in determining subsequent pathology will probably be dependent on the frequency and duration of these episodes, but these have yet to be defined. Prenatal and perinatal sensitization by filarial antigens are postulated to result in tolerance and/or modification of immune responses to subsequent infections. A role for genetic predisposition to certain clinical outcomes, for example, the development of elephantiasis, has been postulated but needs further study. Advances have also been achieved in defining those parasite antigens/products involved in eliciting or suppressing protective and other immune responses.(ABSTRACT TRUNCATED AT 250 WORDS)
  4. Mak JW
    Trop Biomed, 2004 Dec;21(2):39-50.
    PMID: 16493397
    Intestinal protozoa are increasingly being studied because of their association with acute and chronic diarrhoea in immunocompromised as well as immunocompetent patients. Various community outbreaks due to contamination of water or food with these protozoa have further highlighted their importance in public health. Among these important pathogens are Giardia duodenalis, Entamoeba histolytica, Cryptosporidium parvum, Cyclospora cayetanensis, Isospora belli, and microsporidia. Except for the cyst-forming G. duodenalis and E. histolytica, the others are intracellular and form spores which are passed out with the faeces. These organisms are also found in various animals and birds and zoonotic transmission is thought to occur. These infections are distributed worldwide, with a higher prevalence in developing compared to developed countries. However, the relative importance of zoonotic infections especially in developing countries has not been studied in detail. The prevalence rates are generally higher in immunodeficient compared to immunocompetent patients. Higher prevalence rates are also seen in rural compared to urban communities. Most studies on prevalence have been carried out in developed countries where the laboratory and other health infrastructure are more accessible than those in developing countries. This relative inadequacy of laboratory diagnosis can affect accurate estimates of the prevalence of these infections in developing countries. However, reports of these infections in travellers and workers returning from developing countries can provide some indication of the extent of these problems. Most studies on prevalence of amoebiasis in developing countries were based on morphological identification of the parasite in faecal smears. As the pathogenic E. histolytica is morphologically indistinguishable from that of non-pathogenic E. dispar, estimates of amoebiasis may not be accurate. The epidemiology of human microsporidia infections is not completely understood. Two species, Enterocytozoon bieneusi and Encephalitozoon intestinalis, are associated with gastrointestinal disease in humans and it is believed that human to human as well as animal to human infections occur. However, the importance of zoonotic infections has not been fully characterised. G. duodenalis cysts, microsporidia and Cryptosporidium oocysts have been detected in various ground water resources, but their role in community outbreaks and maintenance of the infection has not been fully characterised. The taxonomic classification and pathogenic potential of B. hominis are still controversial. While considered by many as yeast, fungi or protozoon, recent sequence analysis of the complete SSUrRNA gene has placed it within an informal group, the stramenopiles. This review covers recent published data on these zoonotic infections and examines their public health importance in Asian countries.
  5. Mak JW
    Trop Biomed, 2004 Dec;21(2):27-38.
    PMID: 16493396
    Diethylcarbamazine citrate (DEC) has been used for treatment and control of lymphatic filariasis since the 1950s. Although this remarkable drug is still useful and modified strategies in its usage have been developed, a number of newer antifilarial compounds are now available. Numerous field trials evaluating their efficacy in the control of lymphatic filariasis have been conducted. In particular, ivermectin (IVM), albendazole (ALB), and DEC have been tested singly and in combinations and the results of such field studies should be evaluated. While most of the studies were based on efficacy in the clearance of microfilaraemia, a few clinical trials evaluated the adulticidal activity of these compounds. Some antibiotics are effective in killing Wolbachia bacteria symbionts of filarial worms, but their role in the chemotherapy of lymphatic filariasis is still undefined. This review of randomised controlled field studies and randomised controlled clinical trials with these compounds will summarise the findings and give recommendations on their appropriate use for the control and treatment of lymphatic filariasis.
  6. Mak JW
    MyJurnal
    There is no substantial difference in conducting research that is both ethical and responsive to the health needs in developing and developed nations. Differences are in financial constraints, technological expertise in identification and addressing needs, and in the perception of equal partnership of all stakeholders. There will be differences in emphasis of research but this is slowly blurred due to globalisation. Public health emergencies in developing countries need timely and effective global collaborative research to implement control strategies. Research needs should be based on predictive models with learning from past emergencies, technological advances, strategic critical appraisal of local and global health information, and dialogue with all stakeholders. Adequate funding will be challenging and resources from national, international and aid
    foundations will be needed. Issues associated with such funding include deployment of international rapid response teams, collaborating researchers, transfer of technology, and intellectual property ownership. While all types of research ranging from basic, applied, clinical
    studies, meta-analysis, and translational research are relevant, the relative importance and specific allocation of resources to these may differ. Is the choice related to responsiveness or based on researchers’ perception of their contributions to evidence-based practice and research? Ethical issues relating to vulnerable groups, risk distribution, quality issues, research integrity and oversight are just as important. Internationally funded
    research including clinical trials must be sensitive to such issues to avoid allegations of exploitation. Thus the potential of utilisation and buy-in of research findings and recommendations must be considered.
  7. Teo, Keat Seong, Cheah, Cheong Wooi, Mak, Joon Wah
    MyJurnal
    Background: Sensitisation to house dust mite (HDM) has been regarded as a major risk factor for development of asthma. This study was carried out to investigate the profiles of HDM sensitisation among Malaysian children with asthma.
    Material and Methods: The association between HDM sensitisation and control and severity of asthma was investigated. The salivary HDM specific IgE levels were quantified in different grades of control and severity of asthma in 125 unselected asthmatic children aged 5-12 years old attending the asthma follow-up clinic in Hospital Tuanku Ja’afar Seremban. An additional 29 non-asthmatic patients were selected as control. The skin prick test to assess sensitisation to Dermatophagoides pteronyssinus (DP) and Dermatophagoides farinae (DF) was performed on all the participants. A questionnaire regarding the control and severity of asthmatic symptoms of the subject was administered. Saliva was collected by voluntary spitting and ELISA was used to quantify the IgE specific to HDM antigen.
    Results: There was a significant association between sensitisation to DP and DF and the control of asthma. The association between DP sensitisation and severity of asthma just failed to reach a significant level although there is a clear trend for this. Significant association was found between DF sensitisation and severity. The HDM specific IgE in the saliva was significantly higher in asthmatic patients compared to non-asthmatic patients. There was no significant difference between the specific IgE levels in patients with different severity status of asthma.
    Conclusion: Salivary IgE levels may not be an appropriate indicator of the patients’ asthmatic condition in this study. However, it can be concluded that there is significant association between the sensitisation of HDM and the control and severity of asthma.
    Study site: Asthma clinic, Hospital Tuanku Jaafar, Seremban, Negeri Sembilan, Malaysia
  8. Mak JW
    MyJurnal
    Developing and adult worms of the human lymphatic filarial parasites (Wuchereria bancrofti,
    Brugia malayi, and Brugia timori) are located mainly in the lymphatic system and occasionally in aberrant sites like subcutaneous and conjunctival cysts. Lymphatic
    pathology ranging from dilatation of lymphatic channels and lymphangiectasia are detected on ultrasonography in apparently healthy, amicrofilaraemic, but filarial antigen positive individuals in endemic areas. Microfilariae are distributed in various organs and may be associated with immune mediated pathology at these sites; tropical pulmonary eosinophilia is characterized by intense immune mediated destruction of microfilariae in the lung parenchyma. In the spleen and other sites, nodular granulomatous lesions can occur where microfilariae are trapped and destroyed. The finding of Wolbachia endosymbionts in all stages of lymphatic filarial parasites has provided new insight on the adverse reactions
    associated with anti-filarial chemotherapy. Inflammatory molecules mainly lipopolysaccharide (LPS)-like molecules released from endosymbionts on death of the
    parasites are largely responsible for the adverse reactions encountered during anti-filarial chemotherapy. Prenatal tolerance or sensitization to parasite derived molecules can immune-modulate and contribute to both pathology and susceptibility/resistance to infection. Pathological responses thus depend not only on exposure to filarial antigens/infection, but also on host-parasiteendosymbiont factors and to intervention with antifilarial treatment. Treatment induced or host mediated death of parasites are associated with various grades of inflammatory response, in which eosinophils and LPS from endosymbionts play prominent roles, leading to death of the parasite, granulomatous formation, organization and fibrosis. The non-human primate (Presbytis spp.) model of
    Brugia malayi developed for the tertiary screening of anti-filarial compounds has provided unique opportunities for the longitudinal study of the pathology associated with lymphatic filariasis. The pathology in this non-human primate model closely follows that seen in
    human lymphatic filarial infections and correlates with clinical evidence of lymphatic pathology as detected with ultrasonography. These studies also show that successful treatment as detected by loss of motility and calcification of worms on ultrasonography is associated with reversal of early dilatations of lymphatic channels.
  9. Mak JW
    Family Practitioner, 1982;5(3):23-26.
    Brugia malayi and Wuchereria bancrofti infections cause lymphatic filariasis in Malaysia. About 2.5 million people live in endemic areas of filariasis, of whom 5% have microfilaraemia and probably twice as many are infected. There is a wide clinical spectrum of response to the infection. While some have asymptomatic microfilaraemia, others have episodic attacks of fever, lymphadenitis, retrograde lymphangitis and lymphoedema. Elephantiasis is a late complication. Tropical pulmonary eosinophilia and other forms of occult filariasis are due to hyper allergic reactions to microfilarial antigens. Parasitological and serological tests aid in confirming the clinical diagnosis. The drug of choice is diethylcarbamazine citrate.
  10. Naing C, Mak JW
    PMID: 28127542 DOI: 10.1186/s40200-017-0287-5
    BACKGROUND: Incidence of type 1 diabetes mellitus is increasing worldwide. Monitoring glycaemia is essential for control of diabetes mellitus. Conventional blood-based measurement of glucose requires venepuncture or needle prick, which is not free from pain and risk of infection. The non-invasiveness, ease and low-cost in collection made saliva an attractive alternative sample. The objective of this review was to systematically review the evidence on the relationship between salivary glucose level and blood glucose level in monitoring glycaemia in patients with type 1 diabetes mellitus.
    METHODS: We searched studies which evaluate salivary glucose levels and serum glycaemia in type 1 diabetes mellitus in electronic databases of MEDLINE, EMBASE, Ovid and Google Scholar. We selected the eligible studies, following the inclusion criteria set for this review. Due to heterogeneity of studies, we conducted qualitative synthesis of studies.
    RESULTS: Ten observational studies were included in this review, including a total of 321 cases and 323 controls with ages between 3 and 61 years and the majority were males (62%). Two studies were done exclusively on children below 17 years old. The significant difference between salivary glucose levels in type 1 diabetes mellitus and controls were reported in 6 studies with 8 data sets. Five studies with 7 datasets reported the correlation coefficient between salivary glucose and blood glucose in patients with diabetes.
    CONCLUSIONS: Findings suggest that salivary glucose concentrations may be helpful in monitoring glycaemia in type 1 diabetes mellitus. However, the utility of using salivary glucose level to monitor glycaemia should be evaluated in future well designed, prospective studies with adequate number of participants with type 1 diabetes mellitus.
  11. Wong SF, Mak JW
    Hybridoma (Larchmt), 2010 Dec;29(6):539-46.
    PMID: 21117988 DOI: 10.1089/hyb.2010.0049
    Candida parapsilosis has emerged as one of the most common causes of bloodstream infection worldwide. The diagnosis of invasive candidiasis etiological agents to the species level remains a laboratory and clinical challenge. Thus, specific monoclonal antibodies to detect systemic candidiasis and to identify Candida virulence factors and associated pathogenesis through immunohistochemistry would be very useful. Inbred Balb/c mice were immunized with C. parapsilosis antigens, and blood was checked for the presence of reactive antibodies using ELISA. Fusion was performed using the harvested spleen cells and NS1 myeloma cells, and the clones were screened for the presence of antibody producing hybrid cells by dot-blot. The 1B11 clone secreted IgG2a monoclonal antibody that was reactive with the C. parapsilosis antigen at MW of 59 kDa and cross-reacted with C. tropicalis but not with other fungal and bacterial antigens tested. Another 3D1 clone secreted IgG1 monoclonal antibody that was reactive with C. parapsilosis antigen at MW of 30 kDa. The 3D1 monoclonal antibody was found to be species specific. Experimental systemic candidiasis in rats was induced through intravenous injection of C. parapsilosis, and all the vital organs were collected for immunohistochemistry study. These monoclonal antibodies were reactive against surface epitopes on the yeast cells, pseudohyphae, and immune complexes in tissue sections. Sandwich ELISAs using these antibodies were developed and were able to detect circulating antigens in experimental candidiasis in rats at 0.2 μg/μL. These monoclonal antibodies may have potential as primary capture antibodies for the development of rapid diagnostic test for human systemic fungal infection.
  12. Choong MF, Mak JW
    PMID: 1948274
    Hematological changes were monitored in the leaf-monkey, Presbytis cristata, infected experimentally with 200 subperiodic Brugia malayi infective larvae. Prepatent periods were 54-86 days and peak microfilarial geometric mean counts (GMCs) were 1324 per ml blood. Total leukocyte and differential counts were measured at pre-infection, and then at weakly intervals before and during patency. Blood eosinophil level increased to about thrice the initial level at 3 weeks post-infection and this was maintained for the next 13 weeks before it started to rise again, increasing to more than 5 times the initial level at 20 weeks post-infection. The observed pattern of eosinophilia is probably related to the level of microfilaremia and the destruction of microfilariae in the spleen. There was no significant change in the total leukocyte counts during the period of observation.
  13. Ong, Chin-Eng, Yan, Pan, Tiong, Kai-Hung, Yiap, Beow-Chin, Tan, Eng-Lai, Pook, Peter, et al.
    MyJurnal
    Pharmacogenomics (or pharmacogenetics), the study of the effects of genetic differences on a person’s response to drugs, can help in optimizing drug efficacy and minimizing adverse drug reactions. Interperson difference in drug metabolism is one of the important consequences of such genetic variation. This variation is determined in part by mutations in cytochrome P450 enzymes (CYPs). IMU is part of a major collaborative research project in the area of phamacogenetics and drug metabolism. Working together with USM and UiTM, our group has, since 2000, generated useful population database on genetic polymorphism of various CYP isoforms. We have successfully genotyped three major ethnic groups, Malay, Indian and Chinese for their allelic frequency of important isoforms. These include CYP2D6, CYP2C9, CYP2C8 and CYP2A6. Data generated so far collectively have contributed to our effort in mapping and constructing genomic database for Malaysian population.
    Since early 2002, our research has been focusing on developing in vitro methods in studying the functional consequences of genetic polymorphism of CYP enzymes. Using site-directed mutagenesis, CYP mutants, carrying nucleotide changes as reported in known alleles in human populations, were generated and expressed in E. coli system, and the expressed recombinant proteins were characterized using enzyme assays to determine the functional consequences of mutations. We have established a series of HPLC (high performance liquid chromatography)-based and fluorescence-based assays to investigate CYP activities. Assays that have been developed include tolbutamide methylhydroxylase, paclitaxel 6α-hydroxylase, dextromethorphan O-demethylation, testosterone 6β-hydroxylation and coumarin 7-hydroxylase assays. These assays serve as activity markers allowing comparison of catalytic activities of mutant proteins generated. Another focus of our work is to use the developed assays as a screening tool to investigate drug-herb interactions. This was achieved by co-incubation of herbal extracts and active constituents with the probe substrates in the assays followed by characterization of the kinetic behaviors of the enzymes involved using various pharmacokinetic parameters such as Km, Vmax, IC50 and Ki. This work is currently carried out with collaboration from the Institute for Medical Research (IMR) and is supported by MOSTI’s eScienceFund under RM9. It is envisaged that this screening work will give us insights on the potential of the commonly used herbs to cause pharmacokinetic interactions with other drug substrates, and allow us to elucidate the mechanisms involved in the interactions.
  14. Ambu, Stephen, Chu, Wan-Loy, Mak, Joon-Wah, Wong, Shew-Fung, Chan, Li-Li, Wong, Siew-Tung
    MyJurnal
    Malaysia has good environmental laws to protect the outdoor environment and public health. However there are no laws governing indoor air quality (IAQ) and the knowledge among the public about its importance is also lacking. Environmental professionals think it is not a priority and this influences the policy decisions in the country. Therefore there is a need to create awareness by way of research, education and other promotional activities. What is much needed at this time is the establishment of standards for the conduct of risk assessment studies. To establish standards we need reliable data which can be used to develop appropriate guidelines for the purpose of mitigation and adaptation programmes. IAQ can have significant influence on health resulting in drop in productivity and economy of a country. It has been estimated that in the US, building related illnesses (BRI) symptoms have a relationship with decrease (3 to 5%) in work performance in an affected population resulting in an annual loss of US$60 billion in revenue. However, based on efficient management programmes they have also projected that the potential annual savings can be in the region of US$10 to 30 billion. This establishes that fact that good management programmes based on efficient guidelines is of economic value to a country and wellbeing of the population. The IMU has embarked on a research programme to collect the much-needed data for the framing of a good IAQ guideline for Malaysia.
  15. Naing C, Aung K, Mak JW
    J Evid Based Med, 2012 Nov;5(4):232-7.
    PMID: 23557504 DOI: 10.1111/jebm.12002
    In translating clinical research into practice, the summarization of data from randomized trials in terms of measures of effect to be readily appreciated by the point-of-care clinicians is important. In this context, the body of literature highlighted the 'number needed to treat' as a useful measure. The objectives of our study were to assess how meta-analyses described number needed to treat and corresponding 95% CI, and to explore issues related to reporting number needed to treat in the selected meta-analyses.
  16. Pan Y, Mak JW, Ong CE
    Biomed Chromatogr, 2013 Jul;27(7):859-65.
    PMID: 23386533 DOI: 10.1002/bmc.2872
    In this study, a simple and reliable reverse-phase high-performance liquid chromatography (RP-HPLC) method was established and validated to analyze S-mephenytoin 4-hydroxylase activity of a recombinant CYP2C19 system. This system was obtained by co-expressing CYP2C19 and NADPH-CYP oxidoreductase (OxR) proteins in Escherichia coli (E. coli) cells. In addition to RP-HPLC, the expressed proteins were evaluated by immunoblotting and reduced CO difference spectral scanning. The RP-HPLC assay showed good linearity (r(2) = 1.00) with 4-hydroxymephenytoin concentration from 0.100 to 50.0 μm and the limit of detection was 5.00 × 10(-2) μm. Intraday and interday precisions determined were from 1.90 to 8.19% and from 2.20 to 14.9%, respectively. Recovery and accuracy of the assay were from 83.5 to 85.8% and from 95.0 to 105%. Enzyme kinetic parameters (Km , Vmax and Ki ) were comparable to reported values. The presence of CYP2C19 in bacterial membranes was confirmed by immunoblotting and the characteristic absorbance peak at 450 nm was determined in the reduced CO difference spectral assay. Moreover, the activity level of co-expressed OxR was found to be comparable to that of the literature. As a conclusion, the procedures described here have generated catalytically active CYP2C19 and the RP-HPLC assay developed is able to serve as CYP2C19 activity marker for pharmacokinetic drug interaction study in vitro.
  17. Ang HH, Cheang HS, Mak JW
    Chemotherapy, 2005 Oct;51(6):377-80.
    PMID: 16227695
    Exposure of Plasmodium falciparum to increasing sublethal drug concentrations followed by drug treatment led to the development of many resistant parasites. Therefore, the susceptibility of these clones to the type II antifolate drugs, cycloguanil and pyrimethamine, before and after subculturing them in vitro for a period of 3 years, was studied.
  18. Naing C, Lai PK, Mak JW
    BMC Public Health, 2017 08 04;17(1):637.
    PMID: 28778191 DOI: 10.1186/s12889-017-4650-8
    BACKGROUND: This study aimed to estimate potential reductions in case incidence of colorectal cancer attributable to the modifiable risk factors such as alcohol consumption, overweight and physical inactivity amongst the Malaysian population.

    METHODS: Gender specific population-attributable fractions (PAFs) for colorectal cancer in Malaysia were estimated for the three selected risk factors (physical inactivity, overweight, and alcohol consumptions). Exposure prevalence were sourced from a large-scale national representative survey. Risk estimates of the relationship between the exposure of interest and colorectal cancer were obtained from published meta-analyses. The overall PAF was then estimated, using the 2013 national cancer incidence data from the Malaysian Cancer Registry.

    RESULTS: Overall, the mean incidence rate for colorectal cancer in Malaysia from 2008 to 2013 was 21.3 per 100,000 population, with the mean age of 61.6 years (±12.7) and the majority were men (56.6%). Amongst 369 colorectal cancer cases in 2013, 40 cases (20 men, 20 women), 10 cases (9 men, 1 woman) or 20 cases (16 men,4 women) would be prevented, if they had done physical exercises, could reduce their body weight to normal level or avoided alcohol consumption, assuming that these factors are causally related to colorectal cancer. It was estimated that 66 (17.8%;66/369) colorectal cancer cases (42 men, 24 women) who had all these three risk factors for the last 10 years would have been prevented, if they could control these three risk factors through effective preventive measures.

    CONCLUSIONS: Findings suggest that approximately 18% of colorectal cancer cases in Malaysia would be prevented through appropriate preventive measures such as doing regular physical exercises, reducing their body weight to normal level and avoiding alcohol consumption, if these factors are causally related to colorectal cancer. Scaling-up nationwide public health campaigns tailored to increase physical activity, controlling body weight within normal limits and avoid alcohol intake are recommended. Future studies with other site-specific cancers and additional risk factors are needed.

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