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R Ismail

Publications and source records attributed to R Ismail.

At least 19 recordsLinked to original sources
PubMed2003

Standard CYP2D6 genotyping procedures fail for the CYP2D6*5 and duplication alleles when hair roots are used as a source of DNA.

BACKGROUND: Hair roots provide a useful alternative to blood as a source of DNA for genotyping. Besides simple and non-invasive collections, the DNA extraction step is also easy to perform and is fast. The aim of our study is to determine if hair roots can be used to genotype all of the common CYP2D6 alleles for routine screening purposes. METHOD: The study complies with the Declaration of Helsinki. After obtaining informed consents, both blood and hair samples were collected from 92 patients for genotyping of the CYP2D6 gene. PCR was used to detect the following mutations: CYP2D6*1, *3, *4, *5, *9, *10, *17 and duplication gene. The results were compared where hair roots and blood were used as templates for DNA respectively. RESULTS: When blood was used as a source of DNA for genotyping, all of the investigated CYP2D6 alleles were successfully amplified. However, with hair roots, the genes with the larger fragment sizes: CYP2D6*5 and the duplication gene could not be amplified and the bands of other alleles investigated were faint when visualized under UV light. CONCLUSIONS: DNA extraction from hair roots and leucocytes yielded similar results but the DNA extracted from hair roots did not allow successful amplification of the longer genes such as the CYP2D6*5 and the duplication gene.

Alleles↗
PubMed2002

Correlation of tramadol pharmacokinetics and CYP2D6*10 genotype in Malaysian subjects.

The aim of the present study is to investigate the influence of the CYP2D6*10 allele on the disposition of tramadol hydrochloride in Malaysian subjects. A single dose of 100 mg tramadol was given intravenously to 30 healthy orthopaedic patients undergoing various elective surgeries. After having obtained written informed consents, patients were genotyped for CYP2D6*10: the most common CYP2D6 allele among Asians by means of allele-specific polymerase chain reaction. The presence of other mutations (CYP2D6*1, *3, *4, *5, *9 and *17) was also investigated. Tramadol was extracted from 1 ml serum with an n-hexane: ethylacetate combination (4:1) after alkalinisation with ammonia (pH 10.6). Serum concentrations were measured by means of high-performance liquid chromatography. The pharmacokinetics of tramadol was studied during the 24 h after the dose. As among other Asians, the allele frequency for CYP2D6*10 among Malaysians was high (0.43). Subjects who were homozygous for CYP2D6*10 had significantly (P=0.046) longer mean serum half-life of tramadol than subjects of the normal or the heterozygous group (Kruskal-Wallis test). When patients were screened for the presence of other alleles, the pharmacokinetic parameter values were better explained. CYP2D6 activity may play a main role in determining tramadol pharmacokinetics. The CYP2D6*10 allele particularly was associated with higher serum levels of tramadol compared with the CYP2D6*1 allele. However, genotyping for CYP2D6*10 alone is not sufficient to explain tramadol disposition.

Adolescent↗
PubMed2002

Method development and validation of a high-performance liquid chromatographic method for tramadol in human plasma using liquid-liquid extraction.

An HPLC system using a simple liquid-liquid extraction and HPLC with UV detection has been validated to determine tramadol concentration in human plasma. The method developed was selective and linear for concentrations ranging from 10 to 2000 ng/ml with average recovery of 98.63%. The limit of quantitation (LOQ) was 10 ng/ml and the percentage recovery of the internal standard phenacetin was 76.51%. The intra-day accuracy ranged from 87.55 to 105.99% and the inter-day accuracy, 93.44 to 98.43% for tramadol. Good precision (5.32 and 6.67% for intra- and inter-day, respectively) was obtained at LOQ. The method has been applied to determine tramadol concentrations in human plasma samples for a pharmacokinetic study.

Analgesics, Opioid↗
PubMed2002

Removal of iron and manganese by artificial destratification in a tropical climate (Upper Layang Reservoir, Malaysia).

Environmental monitoring was carried out at Upper Layang Reservoir situated in Masai, Johor, Malaysia. The study shows that thermal stratification and natural mixing of the water column do exist in the reservoir and the level of stratification varies at different times of the year. Artificial destratification via diffused air aeration techniques was employed at the reservoir for two months. The results show that thermal stratification was eliminated after a week of continuous aeration. The concentrations of iron and to a lesser extent manganese in the water column was also reduced during the aeration period.

Iron↗
PubMed2001

Comparison of safety and immunogenicity of a Vi polysaccharide typhoid vaccine with a whole-cell killed vaccine in Malaysian Air Force recruits.

OBJECTIVE: To carry out a comparative study of the safety and immunogenicity of Vi polysaccharide vaccine against whole-cell killed (WCK) typhoid vaccine. METHODS: The study was carried out on young adult recruits (aged 18-25 years) of the Malaysian Air Force. A total of 125 subjects received the Vi polysaccharide vaccine and 114 received the WCK vaccine. FINDINGS: The Vi vaccine was significantly less reactogenic than the WCK vaccine with regard to systemic and local reactions. Following administration of the Vi vaccine, seroconversion rates (defined as the percentage of subjects with a 4-fold rise of baseline antibody level) of 75.5% and 67% were observed at 2 weeks and 6 weeks, respectively, after immunization, compared with 25% and 31.3% among recipients of the WCK vaccine. Of the 110 Vi vaccinees with serological data, 21 (19%) had high, seroprotective, pre-immunization levels of anti-Vi antibodies (> or = 1 microgram/ml). The majority of subjects in this group came from a region in Malaysia which is known to have high typhoid endemicity. Interestingly, these antibody levels were boosted considerably following administration of vaccine at a level that was 5-fold higher than in subjects with low pre-immunization levels. In contrast, the seroconversion rates in those receiving the Vi vaccine were higher in subjects with low pre-immunization levels of anti-Vi antibodies (76-84%), compared to those with protective levels of > or = 1 microgram/ml prior to immunization (48-57%). CONCLUSIONS: The study reaffirms the safety and efficacy of the Vi polysaccharide vaccine and identifies a hitherto unrecognized advantage in its use, i.e. it is a potent immunogen that boosted considerably the protective antibody levels among a significant number of immunologically sensitized individuals living in typhoid-endemic regions.

Adolescent↗
PubMed2001

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

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.

Analgesics, Opioid↗
PubMed2001

Heterogeneity of the CYP2D6 gene among Malays in Malaysia.

BACKGROUND: Although Malays shared an origin with Chinese, their evolution saw substantial divergences. Phenotyping studies suggested that they differed in CYP2D6 polymorphism, with higher PM prevalence but lesser right-shift for debrisoquine MRs. OBJECTIVE: To study the genotype distribution of CYP2D6 among the Malays in Malaysia. METHOD: We obtained DNA from 107 Malays and used PCR to determine common CYP2D6 alleles. RESULT: CYP2D6*1 occurred at a frequency of 36.0%, duplicated gene, 0.93%, CYP2D6*4, 2.8%, CYP2D6*5, 5.1%, CYP2D6*9, 3.3%, CYP2D6*10, 49.5% and CYP2D6*17, 0.5%. The findings of CYP2D6*17 and CYP2D6*9 were novel for Asia. The frequency for CYP2D6*10 was lower than in other Asian races. The most frequent genotypes were CYP2D6*1/*10 at 39.3%. Two subjects had genotypes that predicted PM phenotype, 35% showed genotypes that predicted intermediate metabolizers and one subject had a genotype that predicted ultra-rapid metabolism. CONCLUSION: The genetic polymorphism of CYP2D6 in Malays is different from Chinese and Far Eastern races. They may be intermediate between East Asians and Caucasians in CYP2D6 activity. Further study in relation to the evolution of races and disease prevalence may help to identify the contributions of the polymorphism in alleged susceptibility to diseases apart from delineating its contributions to ethnic differences in the pharmacology of CYP2D6 drugs.

Adolescent↗
PubMed2001

Use of the Griffiths Mental Scales in normal 2 year old Malaysian children.

The Griffiths Scales for Mental Development were used to assess a group of 60 normal 2-year old Malaysian children (25 Indian, 23 Malay and 12 Chinese). The mean GQ was 104.2 (SD 9.3). This was significantly higher than the test mean of 100, p < 0.001. The mean score for Malaysian children was significantly higher on the locomotor, personal social, performance and practical reasoning subscales while they were significantly lower on the hand eye subscale and did not differ from the test mean on the hearing and speech subscale. There was a significant correlation between GQ and social class, r = -0.39, p < 0.05. Scores were lower than those currently obtained on British children, p < 0.001. Minor difficulties due to language and cultural factors arose over the interpretation of several items but with standardisation of these items the test is useful in Malaysian children.

Child Development↗
PubMed2000

Stroke.

Explore the source record for details and available documents.

Acute Disease↗
PubMed2000

CYP2D6 phenotypes among Malays in Malaysia.

BACKGROUND: 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. OBJECTIVE: To study debrisoquine metabolism phenotypes in healthy Malay volunteers. METHOD: We administered debrisoquine to 51 Malays and used HPLC to measure urinary debrisoquine and 4-hydroxy debrisoquine to calculate debrisoquine metabolic ratios (MR). RESULTS: Debrisoquine MR varied widely and with probit analysis we were able to identify population subsets. Although the frequency distribution for the MR showed a right shift, the shift was less than that reported for the Chinese population. We also found 2 poor metabolizers and one ultra rapid metaboliser in the population. CONCLUSION: The genetic polymorphism of debrisoquine in Malays differs from that in the Chinese. Both their PM prevalence and their MR distribution suggest that they are intermediate between Europeans and Chinese in relation to this polymorphism. Studies to compare CYP2D6 genotypes between them and related races would be useful to further define these differences.

Adult↗
PubMed2000

Ethnic differences in response to non-selective beta-blockade among racial groups in Malaysia.

OBJECTIVE: To determine whether racial differences in response to blockade of beta receptors occur among racial groups in Malaysia that are the Malays, Indians and Chinese. SUBJECTS, MATERIALS AND METHOD: 35 healthy male volunteers representing the 3 main racial groups in Malaysia (12 Malays, 12 Chinese and 11 Indians) were studied in a randomized, placebo-controlled, crossover and single-blind design. Propranolol 80 mg 12-hourly was given orally for 48 hours. Six hours after the last dose subjects attended an exercise session where resting and exercise heart rate, blood pressure, plasma potassium and glucose levels, resting FEV1 and plasma propranolol concentrations were recorded. RESULTS: No significant difference in plasma propranolol (mean +/- SEM) levels was seen between races six hours after the last dose (Malays, 59.7 +/- 8.8 ng/ml, Indians, 67.6 +/- 19.3 ng/ml, Chinese, 58.4 +/- 7.9 ng/ml). Chinese were least sensitive to the bradycardic and hypotensive effects of propranolol at rest and exercise. Indians and Malays had significant reduction of supine systolic blood pressure with propranolol but not Chinese. Comparison of percentage reductions of systolic blood pressure at supine, sitting and exercise by repeated measure analysis showed the Malays to have significantly higher change compared to the Chinese (p = 0.022). Similarly, comparison of percentage reductions of heart rate at supine, sitting and exercise by repeated measure analysis showed the Malays to have significantly higher change compared to the Chinese (p = 0.040). Average change in potassium concentrations at peak exercise and recovery showed the Indians to have significantly higher increase in potassium levels with propranolol compared to the Malays (p = 0.038). However, no significant interethnic difference was seen in the reduction of glucose levels at rest, peak exercise or recovery. Also, no significant interethnic difference was seen in reduction of FEV1 values. CONCLUSION: We, therefore, conclude that ethnic differences in response to blockade of beta-receptors exist among racial groups in Malaysia. These differences were seen at similar plasma drug levels between races suggesting ethnic differences in drug sensitivity, rather than differences in drug disposition.

Adrenergic beta-Antagonists↗
PubMed1999

Mucocutaneous manifestations of HIV infection: a retrospective analysis of 145 cases in a Chinese population in Malaysia.

BACKGROUND: Mucocutaneous lesions directly related to human immunodeficiency virus (HIV) infection usually present as initial manifestations of immune deficiency. The most common mucocutaneous lesions are Kaposi's sarcoma, histoplasmosis, oro-esophageal candidiasis, oral hairy leukoplakia, and, in Asia, Penicillium marneffei infection. Non-HIV-related skin lesions, such as psoriasis, seborrheic dermatitis, and nodular prurigo, may be the initial presentation among HIV infected patients attending outpatient clinics. METHODS: A retrospective analysis was performed on 145 HIV-positive Malaysians of Chinese descent from two centers at the University Hospital Kuala Lumpur (UHKL) and the General Hospital Kuala Lumpur (GHKL) from March 1997 to February 1998. Demographic data and clinical data were analyzed. RESULTS: The analysis showed that 104 out of 145 patients had mucocutaneous disorders (71.7%). In the study, there were 100 men (96.2%) and four women (3.8%). The majority of patients were in the age group 20-50 years. The patients who presented with mucocutaneous disease also had low CD4+ T-lymphocyte counts and most had acquired immunodeficiency syndrome (AIDS) defining illness. The number of cases with generalized hyperpigmentation was very high in the group (35.9%), followed by nodular prurigo (29.7%) and xerosis (27.6%). Seborrheic dermatitis was seen in 20.7% of cases, with psoriasis in 8.3%. The most common infections were oral candidiasis (35.9%), tinea corporis and onychomycosis (9.7%), and herpes infection (5.5%); however, mucocutaneous manifestations of Kaposi's sarcoma were rare. CONCLUSIONS: The results suggest that mucocutaneous findings are useful clinical predictors of HIV infection or signs of the presence of advanced HIV infection.

Adult↗
PubMed1998

Cloning and expression of the chicken 25-hydroxyvitamin D3 24-hydroxylase cDNA.

Using a cDNA probe from the rat 24-hydrovitamin D3 24-hydroxylase, the chicken 25-hydroxyvitamin D3 24-hydroxylase cDNA has been isolated from a chicken kidney lambda gt11 library. The high degree of similarity with the mammalian 24-hydroxylase cDNAs strongly supports the belief that it is the chicken 25-hydroxyvitamin D3 24-hydroxylase cDNA. The deduced amino acid sequences are also very well conserved and 325 of them are identical among the four known 25-hydroxyvitamin D3 24-hydroxylases. This cDNA expressed in E. coli produces 24-hydroxylase activity.

Amino Acid Sequence↗
PubMed1998

Dynamic assessment of parathyroid function in acute malaria.

OBJECTIVES: To investigate the dynamic parathyroid response to rapidly induced, sustained hypocalcaemia in patients with acute malaria and in healthy volunteers. DESIGN: Serum intact parathormone (PTH) concentrations were measured on samples taken before and during a variable-rate tri-sodium citrate infusion designed to 'clamp' the whole blood ionised calcium concentration 0.20 mmol L-1 below baseline for 120 min. SUBJECTS: Six Malaysian patients aged 17-42 years with acute malaria, four of whom were restudied in convalescence, and 12 healthy controls aged 19-36 years. MAIN OUTCOME MEASURES: Whole-blood ionised calcium and serum intact PTH concentrations. RESULTS: The mean (SD baseline ionised calcium was lower in the malaria patients than in controls (1.09 +/- 0.06 vs. 1.18 +/- 0.03 mmol L-1, respectively; P = 0.01) but PTH concentrations were similar (3.0 +/- 1.8 vs. 3.3 +/- 1.3 pmol L(-1); P = 0.33). Target whole-blood ionised calcium concentrations were achieved more rapidly in the controls than the patients (within 15 vs. 30 min) despite significantly more citrate being required in the patients (area under the citrate infusion-time curve 0.95 (0.25 vs. 0.57 +/- 0.09 mmol kg-1; P < 0.01). The ratio of the change in serum PTH to that in ionised calcium (delta PTH/ delta Ca2+), calculated to adjust for differences in initial rate of fall of ionised calcium, was similar during the first 5 min of the clamp (132 +/- 75 x 10(-6) vs. 131 +/- 43 x 10(-6) in patients and controls, respectively, P > 0.05), as were steady-state serum PTH levels during the second hour (7.0 +/- 2.2 pmol L-1 in each case). Convalescent patients had normal basal ionised calcium levels but the lowest serum intact PTH levels before and during the clamp, consistent with an increase in skeletal PTH sensitivity after treatment. CONCLUSIONS: There is a decreased ionised calcium 'set point' for basal PTH secretion but a normal PTH response to acute hypocalcaemia in malaria. Skeletal resistance may attenuate the effects of the PTH response but patients with malaria appear relatively resistant to the calcium chelating effects of citrated blood products.

Acute Disease↗
PubMed1998

Chloramphenicol in children: dose, plasma levels and clinical effects.

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.

Anemia↗