Displaying publications 1 - 20 of 72 in total

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  1. Lee EJ, Wong JY, Yeoh PN, Gong NH
    Pharmacogenetics, 1995 Oct;5(5):332-4.
    PMID: 8563775
    Glutathione S-transferase-theta (GSTT1) is subject to a genetic polymorphism where approximately 50% of a Caucasian population are homozygous for the null allele. Because of the possible association of the polymorphism with increased cancer risk in individuals, we genotyped by polymerase chain reaction 187 normal Chinese, 167 normal Malays and 152 normal Indians from Singapore and Malaysia. The proportion of Chinese, Malays and Indians with the null genotype were 58%, 38% and 16% respectively and mirrored previously reported frequencies of the GSTM1 null genotype in these populations. The frequency of the combined GSTM1 and GSTT1 null genotypes among Chinese, Malays and Indians were 37%, 22% and 5% respectively. The similarity with predicted frequencies indicated no interaction between the two genetic polymorphisms.
  2. Zhao B, Lee EJ, Wong JY, Yeoh PN, Gong NH
    Pharmacogenetics, 1995 Oct;5(5):275-80.
    PMID: 8563767
    Several xenobiotic metabolizing enzymes, including CYP1A1, NAT2 and GSTM1, are subject to genetic polymorphisms. Because these enzymes are important for the detoxification and/or bioactivation of drugs and carcinogens, these polymorphisms have important implications in therapeutics and cancer susceptibility. The distributions of CYP1A1, NAT2 and GSTM1 genotype frequencies in unrelated individuals of the Indian (n = 139) and Malay (n = 146) populations were characterized by the polymerase chain reaction. The respective allelic frequencies of wild-type and mutant alleles of CYP1A1 were 0.82 and 0.18 for the Indians, and 0.69 and 0.31 for the Malays. The frequencies of wild-type, M1, M2 and M3 of NAT2 among Indians were 0.44, 0.20, 0.32 and 0.04 respectively. The corresponding NAT2 allelic frequencies in Malays were 0.41, 0.12, 0.38 and 0.09. The GSTM1*A allele could not be amplified in 33.1% of Indians and 61.6% of Malays. At least one GSTM1*B allele was detected in 7.2% and 7.5% of the respective populations. The allelic frequencies of CYP1A1, NAT2 and GSTM1 among Malays are similar to previously reported frequencies among Chinese in the region. These findings will be of importance in the determination of cancer risks in these populations.
  3. Goh CR, Lee KS, Tan TC, Wang TL, Tan CH, Wong J, et al.
    Ann Acad Med Singap, 1996 May;25(3):323-34.
    PMID: 8876896
    Quality-of-life assessment has become an accepted method of evaluation in clinical medicine. The technique is based on a patient's self-assessment of physical, psychological, and social function, as well as the effects of distressing physical symptoms. The most important aspect of quality-of-life assessment is that it brings into focus a patient-centred view of health outcome, which is broader than the physiologic measures which predominate in Western medicine. Strategies for the development and use of assessment questionnaires have evolved over the past 15 years, and numerous questionnaires have been created. Most originate in Western societies, with English as the most common language of development. Adapting such questionnaires for use in other language and cultural settings is an imprecise practice. Language translation and equivalent cultural meaning must both be addressed. This paper reports on the language translation process and results for the Functional Living Index for Cancer (FLIC) as translated into Chinese and Malay in Singapore. We employed a step-wise process beginning with translation/back translation, followed by structured pilot field trials and population sampling. Taped versions of the questionnaire were devised to meet illiteracy problems in the sample population. Paired comparisons of the Chinese and Malay versions of individual questions with their English counterparts show good correlations and similar means most of the time. Factor analysis on a population sample of 246 (112 Chinese, 35 Malay and 98 English speaking) with cancers of minimal, extensive or palliative extent is convergent with that obtained on a North American population. However, a separate analysis of the Chinese questionnaires showed some differences in factor pattern. Specific language and cultural translation difficulties are discussed. Of note is the predicted significant decrease in total FLIC scores with extent of disease within each of the language preference populations, which provides some evidence for the validity for each language version in the Singapore culture(s). Thus, the FLIC translations into Malay and Chinese in Singapore can be considered for use in local trials, subject to ongoing evaluation.
  4. Wong EY, Chew PT, Chee CK, Wong JS
    Am J Ophthalmol, 1997 Dec;124(6):797-804.
    PMID: 9402826
    PURPOSE: To evaluate the effectiveness and safety of diode laser contact transscleral cyclophotocoagulation in Asian patients with refractory glaucoma by lower energy settings with an innovative probe featuring a glass ball tip that focused the laser beam onto the ciliary body.

    METHODS: This prospective clinical study included consecutive Asian patients with dark irides and confirmed for glaucoma. Only one eye of each patient was treated. Diode laser contact transscleral cyclophotocoagulation treatment was performed with the center of the probe placed 1.5 mm behind the limbus. About 30 pulses of 810-mm laser radiation (power, 1.8 to 2.0 W; duration, 0.3 to 0.5 second) were applied around the eye. Patients were examined at fixed postoperative intervals. Intraocular pressure levels and postoperative complications were recorded. The relation between patient and disease characteristics, total laser energy delivered, and intraocular pressure effects were analyzed.

    RESULTS: Thirty-three patients were studied, with a mean follow-up period of 9.4 months. An average 56% of patients showed a 30% or greater drop in intraocular pressure. About 38% of patients achieved sustained intraocular pressure lowering to below 22 mm Hg at 18 months. Complications were few and included transient hypotony and iritis.

    CONCLUSIONS: In Asian patients with refractory glaucoma or painful glaucomatous eyes with poor visual acuity (defined for this study as worse than 20/200), low-energy-setting diode laser contact transscleral cyclophotocoagulation by means of the glass ball probe is relatively effective and safe.

  5. Peh KK, Yuen KH, Wong JW, Toh WT
    Drug Dev Ind Pharm, 1999 Mar;25(3):357-60.
    PMID: 10071830
    A study was conducted to compare the bioavailability of a generic product of atenolol (Normaten FC) with the innovator product, Tenormin. Twelve healthy adult volunteers participated in the study conducted according to a randomized, two-way crossover design. The preparations were compared using area under the plasma concentration-time curve AUC0-infinity, peak plasma concentration Cmax, and time to reach peak plasma concentration Tmax. No statistically significant difference was obtained between the Tmax values and the logarithmic transformed AUC0-infinity and Cmax values of the two products. Moreover, the 90% confidence interval for the ratio of the logarithmically transformed AUC0-infinity values of Normaten FC over those of Tenormin was found to lie between 0.82 and 0.98, while that of the logarithmically transformed Cmax values was between 0.82 and 1.09, both being within the bioequivalence limit of 0.80-1.25. The values of elimination half-life t1/2 between the two products were also found comparable and not significantly different statistically. The t1/2 values obtained in our study were slightly longer than those reported in the literature for other population groups.
  6. Yuen KH, Wong JW, Billa N, Julianto T, Toh WT
    Int J Clin Pharmacol Ther, 1999 Jul;37(7):319-22.
    PMID: 10442505
    The bioavailability of a generic preparation of metformin (Diabetmin from Hovid Sdn Bhd) was evaluated in comparison with a proprietary product (Glucophage from Lipha Pharma Ltd., UK).
  7. Yuen KH, Wong JW, Billa N, Choy WP, Julianto T
    Med J Malaysia, 1999 Dec;54(4):482-6.
    PMID: 11072466
    The bioavailability of a generic preparation of ketoconazole (Zorinax from Xepa-Soul Pattinson, Malaysia) was evaluated in comparison with the innovator product (Nizoral from Janssen Pharmaceutica, Switzerland). Eighteen healthy male volunteers participated in the study conducted according to a two-way crossover design. The bioavailability was compared using the parameters, total area under the plasma concentration-time curve (AUC0-infinity), peak plasma concentration (Cmax) and time to reach peak plasma concentration (Tmax). No statistically significant difference was observed between the values of the two products in all the three parameters. Moreover, the 90% confidence interval for the ratio of the logarithmic transformed AUC0-infinity and Cmax values of Zorinax over Nizoral was found to lie between 0.82-1.04 and 0.83-1.02, respectively, being within the acceptable equivalence limit of 0.80-1.25. These findings indicate that the two preparations are comparable in the extent and rate of absorption. In addition, the elimination rate constant (ke) and apparent volume of distribution (Vd) were calculated. For both parameters, there was no statistically significant difference between the values obtained from the data of the two preparations. Moreover, the values are comparable to those reported in the literature.
  8. Yap SP, Julianto T, Wong JW, Yuen KH
    J Chromatogr B Biomed Sci Appl, 1999 Dec 10;735(2):279-83.
    PMID: 10670741
    A simple high-performance liquid chromatographic method using fluorescence detection was developed for the determination of vitamin E especially delta-, gamma- and alpha-tocotrienols in human plasma. The method entailed direct injection of plasma sample after deproteinization using a 3:2 mixture of acetonitrile-tetrahydrofuran. The mobile phase comprised 0.5% (v/v) of distilled water in methanol. Analyses were run at a flow-rate of 1.5 ml/min with the detector operating at an excitation wavelength of 296 nm and emission wavelength of 330 nm. This method is specific and sensitive, with a quantification limit of approximately 40, 34 and 16 ng/ml for alpha-, gamma- and delta-tocotrienol, respectively. The mean absolute recovery values were about 98% while the within-day and between-day relative standard deviation and percent error values of the assay method were all less than 12.0% for alpha-, gamma- and delta-tocotrienol. The calibration curve was linear over a concentration range of 40-2500, 30-4000 and 16-1000 ng/ml for alpha-, gamma- and delta-tocotrienol, respectively. Application of the method in a bioavailability study for determination of the above compounds was also demonstrated.
  9. Lim CC, Sitoh YY, Hui F, Lee KE, Ang BS, Lim E, et al.
    AJNR Am J Neuroradiol, 2000 Mar;21(3):455-61.
    PMID: 10730635
    BACKGROUND AND PURPOSE: An epidemic of suspected Japanese encephalitis occurred in Malaysia in 1998-1999 among pig farmers. In neighboring Singapore, an outbreak occurred among pig slaughterhouse workers. It was subsequently established that the causative agent in the outbreak was not the Japanese encephalitis virus but a previously unknown Hendra-like paramyxovirus named Nipah virus.

    METHODS: The brain MR images of eight patients with Nipah virus infection were reviewed. All patients tested negative for acute Japanese encephalitis virus. Seven patients had contrast-enhanced studies and six had diffusion-weighted examinations.

    RESULTS: All patients had multiple small bilateral foci of T2 prolongation within the subcortical and deep white matter. The periventricular region and corpus callosum were also involved. In addition to white matter disease, five patients had cortical lesions, three had brain stem involvement, and a single thalamic lesion was detected in one patient. All lesions were less than 1 cm in maximum diameter. In five patients, diffusion-weighted images showed increased signal. Four patients had leptomeningeal enhancement and four had enhancement of parenchymal lesions.

    CONCLUSION: The brain MR findings in patients infected with the newly discovered Nipah paramyxovirus are different from those of patients with Japanese encephalitis. In a zoonotic epidemic, this striking difference in the appearance and distribution of lesions is useful in differentiating these diseases. Diffusion-weighted imaging was advantageous in increasing lesion conspicuity.

  10. Yuen KH, Wong JW, Peh KK, Julianto T, Choy WP
    Drug Dev Ind Pharm, 2000 Jul;26(7):803-7.
    PMID: 10872103
    The bioavailability of a generic preparation of pentoxifylline sustained-release (SR) tablet was evaluated in comparison with a proprietary product (Trental 400). For the study, 12 healthy male volunteers participated; the study was conducted according to a randomized, two-way crossover design. The bioavailability was compared using the parameters total area under the plasma level-time curve AUC0-infinity, peak plasma concentration Cmax, and time to reach peak plasma concentration Tmax. No statistically significant difference was observed between the values of the two products in all three parameters. The 90% confidence interval for the ratio of the logarithmic transformed AUC0-infinity values of the generic pentoxifylline over those of Trental 400 was found to lie between 0.83 and 1.00, while that of the parameter Cmax was between 0.91 and 1.29. In addition, elimination half-life t1/2 and apparent volume of distribution Vd were calculated. There was no statistically significant difference between the t1/2 Vd values obtained from the data of the two preparations.
  11. Yuen KH, Wong JW, Yap SP, Billa N
    Int J Clin Pharmacol Ther, 2001 Jan;39(1):37-40.
    PMID: 11204936
    OBJECTIVE: The aim of the present communication is to provide information regarding the intrasubject coefficent of variation obtained from 30 bioequivalence studies covering 16 drugs which can be used for estimation of sample size. Additionally, an attempt was also made to estimate the test power of each of the studies conducted.

    METHODS: The intrasubject coefficient of variation was estimated from the residual mean square error obtained from analysis of variance of the parameters AUC0-infinity, Cmax and Cmax/AUC0-infinity after logarithmic transformation. The test power in the analyses of the above parameters was subsequently estimated using nomograms provided by Diletti et al. [1991].

    RESULTS AND CONCLUSION: Thirty products covering 16 drugs were studied in which 22 were immediate-release (including one dispersible tablet) and 8 were sustained-release formulations. The intrasubject coefficient of variation for the parameter AUC0-infinity was smaller than Cmax, and hence considerably more studies were able to attain a power of greater than 80% using 12 volunteers for the AUC0-infinity, compared to the Cmax. However, the variability in the Cmax could be reduced by using the parameter Cmax/ AUC0-infinity, and thus, provide a more realistic estimation of sample size, since the latter reflects only the rate of absorption and not both the rate and extent as in the case of Cmax [Endrenyi et al. 1991].

  12. Yap SP, Yuen KH, Wong JW
    J Pharm Pharmacol, 2001 Jan;53(1):67-71.
    PMID: 11206194
    We have investigated the pharmacokinetics and bioavailability of alpha-, gamma- and delta-tocotrienols under fed and fasted conditions in eight healthy volunteers. The volunteers were administered a single oral dose of mixed tocotrienols (300 mg) under fed or fasted conditions. The bioavailability of tocotrienols under the two conditions was compared using the parameters peak plasma concentration (Cmax), time to reach peak plasma concentration (Tmax) and total area under the plasma concentration-time curve (AUC(o-infinity)). A statistically significant difference was observed between the fed and fasted logarithmic transformed values of Cmax (P < 0.01) and AUC(0-infinity) (P < 0.01) for all three tocotrienols. In addition, the 90% confidence intervals for the ratio of the logarithmic transformed AUC(0-infinity) values of alpha-, gamma- and delta-tocotrienols under the fed state over those of the fasted state were found to lie between 2.24-3.40, 2.05-4.09 and 1.59-3.81, respectively, while those of the Cmax were between 2.28-4.39, 2.31-5.87 and 1.52-4.05, respectively. However, no statistically significant difference was observed between the fed and fasted Tmax values of the three homologues. The mean apparent elimination half-life (t(1/2)) of alpha-, gamma- and delta-tocotrienols was estimated to be 4.4, 4.3 and 2.3 h, respectively, being between 4.5- to 8.7-fold shorter than that reported for alpha-tocopherol. No statistically significant difference was observed between the fed and fasted t(1/2) values. The mean apparent volume of distribution (Vd/f) values under the fed state were significantly smaller than those of the fasted state, which could be attributed to increased absorption of the tocotrienols in the fed state.
  13. Yuen KH, Choy WP, Tan HY, Wong JW, Yap SP
    J Pharm Biomed Anal, 2001 Feb;24(4):715-9.
    PMID: 11272330
    A simple high-performance liquid chromatographic method was developed for the determination of omeprazole in human plasma. Omeprazole and the internal standard, chloramphenicol, were extracted from alkalinized plasma samples using dichloromethane. The mobile phase was 0.05 M Na2HPO4-ACN (65:35, v/v) adjusted to pH 6.5. Analysis was run at a flow rate of 1.0 ml/min at a detection wavelength of 302 nm. The method was specific and sensitive with a detection limit of 2.5 ng/ml at a signal-to-noise ratio of 4:1. The limit of quantification was set at 5 ng/ml. The calibration curve was linear over a concentration range of 5-1280 ng/ml. Mean recovery value of the extraction procedure was about 96%, while the within and between day coefficient of variation and percent error values of the assay method were all less than 14%.
  14. Wong JW, Yuen KH
    Int J Pharm, 2001 Oct 04;227(1-2):177-85.
    PMID: 11564552
    The bioavailability of beta- and gamma-cyclodextrin artemisinin complexes was evaluated in comparison with a normal commercially available preparation, Artemisinin 250. Twelve healthy male volunteers participated in the study conducted according to a three-way crossover design. The bioavailability was compared using the parameters, total area under the plasma level-time curve (AUC(0-infinity)), peak plasma concentration (C(max)), and time to reach peak plasma concentration (T(max)). A statistically significant difference was observed between the values of the complexes and Artemisinin 250 for the three parameters. However, no statistically significant difference was observed between the values of the beta- and gamma-cyclodextrin complexes. Moreover, the 90% confidence interval for the ratio of the AUC(0-infinity) values of the beta-cyclodextrin complex over those of Artemisinin 250 was estimated to be between 1.51-2.04, while that of C(max) was between 1.73-2.93. For the gamma-cyclodextrin complex, the respective intervals were 1.30-1.76 and 1.43-2.43. These findings indicated that the beta- and gamma-cyclodextrin complexes had a much higher rate and extent of bioavailability compared to Artemisinin 250. In addition, the absorption of artemisinin was observed to be poor and negligible when the preparations started to arrive in the colon. This could be attributed to poor dissolution of artemisinin in the semi-solid faecal matter in the lower part of the gastrointestinal tract.
  15. Wong JW, Yuen KH, Nagappan S, Shahul WS, Ho SS, Gan EK, et al.
    J Pharm Pharmacol, 2003 Feb;55(2):193-8.
    PMID: 12631411
    We have evaluated the therapeutic equivalence of a beta-cyclodextrin-artemisinin complex at an artemisinin dose of 150 mg, with a commercial reference preparation, Artemisinin 250 at a recommended dose of 250 mg. One hundred uncomplicated falciparum malarial patients were randomly assigned to orally receive either beta-cyclodextrin-artemisinin complex (containing 150 mg artemisinin) twice daily for five days or the active comparator (containing 250 mg artemisinin) twice daily for five days. The patients were hospitalized for seven days and were required to attend follow up assessments on days 14, 21, 28 and 35. All patients in both treatment groups were cured of the infection and achieved therapeutic success. At day seven of treatment, all patient blood was clear of the parasites and the sublingual temperature of all patients was less than 37.5 degrees C. Moreover, the parasite clearance time in both treatment groups was similar, being approximately three days after initiation of treatment. Comparable plasma artemisinin concentrations were observed between patients in both treatment groups at 1.5 and 3.0 h, although slightly higher levels were obtained with patients in the beta-cyclodextrin-artemisinin complex-treated group. The beta-cyclodextrin-artemisinin complex at a dose of 150 mg artemisinin was therapeutically equivalent to 250 mg Artemisinin 250. Additionally, patients receiving beta-cyclodextrin-artemisinin complex showed less variability in their plasma artemisinin concentrations at 1.5 h post-dosing, which suggested a more consistent rate of drug absorption.
  16. Wong JW, Yuen KH
    Drug Dev Ind Pharm, 2003 Oct;29(9):1035-44.
    PMID: 14606667
    The present study was conducted to investigate the inclusion complexation of artemisinin (ART) with natural cyclodextrins (CyD), namely alpha-, beta-, and gamma-CyDs with the aim of improving its solubility and dissolution rate. Complex formation in aqueous solution and solid state was studied by solubility analysis, dissolution, and thermal analysis. Solubility diagrams indicated that the complexation of ART and the three CyDs occurred at a molar ratio of 1:1, and showed a remarkable increase in ART solubility. Moreover, the thermodynamic parameters calculated by using the van't Hoff equation revealed that the complexation process was associated with negative enthalpy of formation and occurred spontaneously. The complexation capability of CyDs with ART increased in the order of alpha- < gamma- < beta-CyDs and could be ascribed to the structural compatibility between the molecular size of ART and the diameter of the CyD cavities. Dissolution profiles of the three complexes demonstrated an increased rate and extent of dissolution compared with those of their respective physical mixtures and a commercial preparation. In solid-state analysis, using differential scanning calorimetry, the gamma-CyD was capable of complexing the highest percentage of ART, followed by beta- and alpha-CyDs. The respective estimated percentage of ART complexed by the CyDs were 85%, 40%, and 12%.
  17. Wong JS, Ng KH, Wong SH
    J Clin Neurosci, 2004 Apr;11(3):254-8.
    PMID: 14975412
    This is a prospective study conducted from February 2000 to July 2002 in a single neurosurgeon neurosurgical service in the state of Sarawak, Malaysia. There were 66 cases of subarachnoid hemorrhage or intracranial aneurysm presenting to this hospital over the study period. Fifty cases had their aneurysms clipped. Eighty percent of our patients were operated within 48 h of presentation. Forty-four percent presented with poor WFNS grades of 4 and 5. We had a 20% operative mortality and 29% total management mortality. Twenty-nine (58%) of the operated cases had a favorable outcome with a mean follow-up of 32 weeks. Multiple aneurysms were less common. The diagnosis of aneuysmal subarachnoid hemorrhage and clipping of aneurysms have increased dramatically over the previous two and half years indicating an increased awareness of the diagnosis and treatment. This series supports the previously reported beliefs that the lower rate of aneurymal subarachnoid hemorrhage in developing countries is likely due to both underdiagnosis and undertreatment. Good results can be achieved in developing countries with early diagnosis and intensive management.
  18. Wong JS, Rahimah N
    Med J Malaysia, 2004 Aug;59(3):411-7.
    PMID: 15727390 MyJurnal
    Achieving glycaemic goals in diabetics has always been a problem, especially in a developing country with inadequate facilities such as in Sarawak in Malaysia. There are no reported studies on the control of diabetes mellitus in a diabetic clinic in the primary health care setting in Sarawak. This paper describes the profile of 1031 patients treated in Klinik Kesihatan Tanah Puteh Health Centre. The mean age was 59 years, the mean BMI 27 kg/m2. There was a female preponderance and mainly type-2 diabetes. Mean HbA1c was 7.4%. Glycaemic control was optimal in 28% (HbA1c <6.5%), fair in 34% (HbA1c 6.5-7.5%) and poor in 38% (HbA1c >7.5%). Reasonable glycaemic control can be achieved in the primary health care setting in Sarawak.
    Study site: Klinik Kesihatan Tanah Puteh, Sarawak, Malaysia
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