BACKGROUND: Cardiovascular diseases are complex diseases that are influenced by both environmental and genetic factors. CYP2D6 found in the brain and the heart is involved in the metabolism of many environmental and some endogenous substances and neurotransmitters responsible for maintaining homeostasis. This raises an interesting hypothesis that it may have a role in the development of or protection against cardiovascular diseases.
OBJECTIVE: To study the distribution of genotypes of CYP2D6 among patients with cardiovascular diseases in Malaysia.
METHOD:We obtained DNA from 128 patients who were followed up for cardiovascular diseases. Polymerase chain reaction-based methods were used to determine common CYP2D6 alleles.
RESULTS: One hundred and twenty-eight patients were enrolled. Most of the patients also had concurrent illnesses. Eleven genotypes were identified in the patients and 41% carried CYP2D6*1/*10. The second most common genotype was homozygous for the wild type gene, followed by homozygous CYP2D6*10/*10 at 14.48 %. A small percentage of the patients were heterozygous CYP2D6*1/*4. One patient was genotyped homozygous CYP2D6*4/*4 predicting a poor metabolizer prevalence of 0.78% (95% CI +/- 1.52%). Analysis using Hardy-Weinberg equilibrium showed that all of the gnotypes were consistent with equilibrium except for CYP2D6*1/*10 (chi(2); P < 0.05).
CONCLUSION: Our study suggests a possible involvement of CYP2D6 genotypes in cardiovascular system diseases, which need to be validated by further studies.
A novel fiber tapering shape, which is based on compound parabolic geometry, is proposed to increase the acceptance angle of a compound parabolic concentrator. The proposed design is described by use of ray optics on a step-index multimode fiber.
MeSH terms: Dietary Fiber; Laxatives; Optics and Photonics
DNA technology provides a new avenue to perform neonatal screening tests for single-gene diseases in populations of high frequency. Thalassemia is one of the high-frequency single-gene disorders affecting Singapore and many countries in the malaria belt. The authors explored the feasibility of using PCR-based diagnostic screening on 1,116 unselected sequential cord blood samples for neonatal screening. The cord blood samples were screened for the most common reported alpha- and beta-thalassemia mutations in each ethnic group (Chinese, Malays, and Indians) in a multiracial population. The carrier frequency for alpha-thalassemia mutations was about 6.4% in the Chinese (alpha deletions = 3.9%, alpha deletions = 2.5%), 4.8% in Malays, and 5.2% in Indians. Only alpha deletions were observed in the Chinese. The carrier frequency for beta-thalassemia mutations was 2.7% in the Chinese, 6.3% in Malays, and 0.7% in Indians. Extrapolating to the population distribution of Singapore, the authors found a higher overall expected carrier frequency for alpha- and beta-thalassemia mutations of 9% compared with a previous population study of 6% by phenotype. The highly accurate results make this molecular epidemiologic screening an ideal method to screen for and prevent severe thalassemia in high-risk populations.
Nucleotide sequence comparison of the L gene of the Malaysian neurotropic-viscerotropic velogenic NDV strain AF2240 with other NDV strains revealed a single nucleotide insertion at position 3870. This mutation is compensated by a nucleotide deletion downstream at position 3958 which results in two forms of the L proteins containing a 30-amino acid substitution in Domain V. This compensatory mutation does not correlate with the pathogenicity of the viral strains but it may affect the viral replication as Domain V is believed to play an important role in the replication of paramyxoviruses.
The effect of organic solvent on the structure and dynamics of proteins was investigated by multiple molecular dynamics simulations (1 ns each) of Candida rugosa lipase in water and in carbon tetrachloride. The choice of solvent had only a minor structural effect. For both solvents the open and the closed conformation of the lipase were near to their experimental X-ray structures (C(alpha) rms deviation 1-1.3 A). However, the solvents had a highly specific effect on the flexibility of solvent-exposed side chains: polar side chains were more flexible in water, but less flexible in organic solvent. In contrast, hydrophobic residues were more flexible in organic solvent, but less flexible in water. As a major effect solvent changed the dynamics of the lid, a mobile element involved in activation of the lipase, which fluctuated as a rigid body about its average position. While in water the deviations were about 1.6 A, organic solvent reduced flexibility to 0.9 A. This increase rigidity was caused by two salt bridges (Lys85-Asp284, Lys75-Asp79) and a stable hydrogen bond (Lys75-Asn 292) in organic solvent. Thus, organic solvents stabilize the lid but render the side chains in the hydrophobic substrate-binding site more mobile. [figure: see text]. Superimposition of open (black, PDB entry 1CRL) and closed (gray, PDB entry 1TRH) conformers of C. rugosa lipase. The mobile lid is indicated.
An ergonomics improvement study was conducted on the visual inspection process of a printed circuit assembly (PCA) factory. The process was studied through subjective assessment and direct observation. Three problems were identified: operators' eye problems, insufficient time for inspection and ineffective visual inspection. These problems caused a huge yearly rejection cost of US 298,240 dollars, poor quality, customer dissatisfaction and poor occupational health and safety. Ergonomics interventions were made to rectify the problems: reduced usage of a magnifying glass, the use of less glaring inspection templates, inspection of only electrically non-tested components and introduction of a visual inspection sequence. The interventions produced savings in rejection cost, reduced operators' eye strain, headaches and watery eyes, lowered the defect percentage at customers' sites and increased the factory's productivity and customer satisfaction.
Beta-thalassemia is the most-common genetic disorder of hemoglobin synthesis in Malaysia, and about 4.5% of the population are heterozygous carriers of the disorder. Prenatal diagnosis was performed for 96 couples using the Amplification Refractory Mutation System and Gap-Polymerase Chain Reaction. We identified 17 beta-globin defects-initiation codon for translation (T-G), -29 (A-G), -28 (A-G), CAP +1 (A-C), CD 8/9 (+G), CD 15 (G-A), CD 17 (A-T), CD 19 (A-G), Hb E (G-A), IVS1-1 (G-T), IVS1-5 (G-C), CD 41/42 (-CTTT), CD 71-72 (+A), IVS2-654 (CT), poly A(A-G), 100-kb Ggamma(Agammadeltabeta) degrees and 45-kb Filipino deletions. The 192 beta-alleles studied comprised Chinese (151 patients), Malay (21), Orang Asli from East Malaysia (15), Filipino (1), Indian (1), Indonesian Chinese (2), and Thai (1). In the Chinese, 2 beta-globin defects at CD 41/42 and IVS2-654 were responsible for 74% of beta-thalassemia. beta-mutations at CD 19, IVS1-1 (G-T), IVS1-5, poly A, and hemoglobin E caused 76% of the hemoglobin disorders in the Malays. The Filipino 45-kb deletion caused 73.3% of bthalassemia in the Orang Asli. Using genomic sequencing, the rare Chinese beta-mutation at CD 43 (G-T) was confirmed in 2 Chinese, and the Mediterranean mutation IVS1-1 (G-A) was observed in a Malay beta-thalassemia carrier. The beta-globin mutations confirmed in this prenatal diagnosis study were heterogenous and 65 (68%) couples showed a different globin defect from each other. The use of specific molecular protocols has allowed rapid and successful prenatal diagnosis of beta-thalassemia in Malaysia.
The last three decades have seen an alarming number of high-profile outbreaks of new viruses and other pathogens, many of them emerging from wildlife. Recent outbreaks of SARS, avian influenza, and others highlight emerging zoonotic diseases as one of the key threats to global health. Similar emerging diseases have been reported in wildlife populations, resulting in mass mortalities, population declines, and even extinctions. In this paper, we highlight three examples of emerging pathogens: Nipah and Hendra virus, which emerged in Malaysia and Australia in the 1990s respectively, with recent outbreaks caused by similar viruses in India in 2000 and Bangladesh in 2004; West Nile virus, which emerged in the New World in 1999; and amphibian chytridiomycosis, which has emerged globally as a threat to amphibian populations and a major cause of amphibian population declines. We discuss a new, conservation medicine approach to emerging diseases that integrates veterinary, medical, ecologic, and other sciences in interdisciplinary teams. These teams investigate the causes of emergence, analyze the underlying drivers, and attempt to define common rules governing emergence for human, wildlife, and plant EIDs. The ultimate goal is a risk analysis that allows us to predict future emergence of known and unknown pathogens.
MeSH terms: Amphibians/microbiology; Animals; Conservation of Natural Resources*; Disease Outbreaks*; Ecology*; Forecasting; Humans; Interprofessional Relations*; Chytridiomycota/pathogenicity; Public Health; Veterinary Medicine/trends; West Nile virus/pathogenicity; Zoonoses*; Clinical Medicine/trends*; Risk Assessment; Communicable Diseases, Emerging/diagnosis; Communicable Diseases, Emerging/epidemiology; Communicable Diseases, Emerging/therapy*; Hendra Virus/pathogenicity
Concerns about professionalism in medicine have made necessary the explicit teaching and learning of ethics, professionalism and personal development. The noble profession of medicine, taken up as a "calling" by those who are expected to put the needs of the patient above their own, appears to have become a fees-for-service business model and trade. Parental expectations, the diminishing sense of responsibility in teachers, lack of role models, technological advancements, sub-specialisation and third-party involvement in the healthcare delivery system have been identified as reasons for these concerns. The General Medical Council in the United Kingdom, and other professional bodies in both Europe and the Americas, have emphasised the need to enhance the teaching and learning of professionalism in medical schools, particularly the development of good attitudes, appropriate and competent skills, and the inculcation of a value system that reflects the tenets of professionalism in medicine. The medical curriculum will need to be scrutinised so as to introduce the subject of professionalism at all levels of training and education. Barriers to learning professionalism have been identified and students need to be equipped to resolve conflicts and to put the needs of others above their own.
During the last three decades, several techniques have been proposed for signal-to-noise ratio (SNR) and noise variance estimation in images, with different degrees of success. Recently, a novel technique based on the statistical autoregressive model (AR) was developed and proposed as a solution to SNR estimation in scanning electron microscope (SEM) image. In this paper, the efficiency of the developed technique with different imaging systems is proven and presented as an optimum solution to image noise variance and SNR estimation problems. Simulation results are carried out with images like Lena, remote sensing, and SEM. The two image parameters, SNR and noise variance, are estimated using different techniques and are compared with the AR-based estimator.
A new technique based on the statistical autoregressive (AR) model has recently been developed as a solution to signal-to-noise (SNR) estimation in scanning electron microscope (SEM) images. In the present study, we propose to cascade the Lagrange time delay (LTD) estimator with the AR model. We call this technique the mixed Lagrange time delay estimation autoregressive (MLTDEAR) model. In a few test cases involving different images, this model is found to present an optimum solution for SNR estimation problems under different noise environments. In addition, it requires only a small filter order and has no noticeable estimation bias. The performance of the proposed estimator is compared with three existing methods: simple method, first-order linear interpolator, and AR-based estimator over several images. The efficiency of the MLTDEAR estimator, being more robust with noise, is significantly greater than that of the other three methods.
Cannon's disease or white sponge naevus is a relatively rare genetically determined skin disorder. It is inherited as an autosomal dominant trait that displays a high degree of penetrance and expressivity. This article describes cases of Cannon's disease in a mother and her son.
We propose the use of a truncated ball lens in a collimating system to transform a spherical wave from a highly divergent source into a plane wave. The proposed scheme, which incorporates a hyperbolic lens, is discussed, and the overall system is found to have a large acceptance angle and to be free of spherical aberration. Diffraction and polarization effects are neglected, as well as skew rays.
Ethnic differences in bone density and hip geometry are known to exist, even within the same population. A recent study in Singapore showed that there were significant racial differences in hip fracture rates, with Chinese having the highest incidence of hip fractures. The aim of this study was to compare the bone mineral density (BMD) and hip axis length in Chinese, Malay, and Indian women. A total of 1575 women aged 20-59 yr were recruited, of which 77.6% (1222) were Chinese, 7.7% (122) Malays, and 14.7% (231) Indians. There was no significant difference in peak BMD of both lumbar spine and femoral neck among the three ethnic groups. However, in the older age group (50-59 yr), both Chinese and Malay women had significantly lower femoral neck BMD compared to Indian women. There was no significant loss in BMD of the lumbar spine between the second and fifth decades in all the three races. Between the second and fifth decade, Chinese and Malay women had significant bone loss in the femoral neck of 6.6% and 8.2%, respectively, whereas Indian women did not show any significant bone loss. Chinese women had significantly longer hip axis length compared to either Malay or Indian women (9.87 +/- 0.52 cm vs 9.67 +/- 0.49 cm; p < 0.005; and 9.69 +/- 0.55 cm, p < 0.05, respectively). The initial findings suggest racial differences in bone density and hip geometry exist in the local community. Future research should include prospective, longitudinal studies to determine the age-related bone loss in these three racial groups. It is also important to investigate the differences of spine and hip fracture rates and their relationship with bone density and hip axis length.
MeSH terms: Adult; Age Factors; Body Height/physiology; Body Weight/physiology; China/ethnology; Ethnic Groups*; Female; Femur Neck/anatomy & histology; Hip Joint/anatomy & histology*; Humans; India/ethnology; Lumbar Vertebrae/anatomy & histology; Malaysia/ethnology; Male; Middle Aged; Singapore; Cohort Studies; Bone Density/physiology*; European Continental Ancestry Group; Asian Continental Ancestry Group
Tropical Africa is not the only area where deadly viruses have recently emerged. In South-East Asia severe epidemics of dengue hemorrhagic fever started in 1954 and flu pandemics have originated from China such as the Asian flu (H2N2) in 1957, the Hong-Kong flu (H3N2) in 1968, and the Russian flu (H1N1) in 1977. However, it is especially during the last ten years that very dangerous viruses for mankind have repeatedly developed in Asia, with the occurrence of Alkhurma hemorrhagic fever in Saudi Arabia (1995), avian flu (H5N1) in Hong-Kong (1997), Nipah virus encephalitis in Malaysia (1998,) and, above all, the SARS pandemic fever from Southern China (2002). The evolution of these viral diseases was probably not directly affected by climate change. In fact, their emergential success may be better explained by the development of large industry poultry flocks increasing the risks of epizootics, dietary habits, economic and demographic constraints, and negligence in the surveillance and reporting of the first cases.
Four methods were developed for the analysis of fluroxypyr in soil samples from oil palm plantations. The first method involved the extraction of the herbicide with 0.05 M NaOH in methanol followed by purification using acid base partition. The concentrated material was subjected to derivatization and then cleaning process using a florisil column and finally analyzed by gas chromatography (GC) equipped with electron capture detector (ECD). By this method, the recovery of fluroxypyr from the spiked soil ranged from 70 to 104% with the minimum detection limit at 5 microg/kg. The second method involved solid liquid extraction of fluroxypyr using a horizontal shaker followed by quantification using high performance liquid chromatography (HPLC) equipped with UV detector. The recovery of fluroxypyr using this method, ranged from 80 to 120% when the soil was spiked with fluroxypyr at 0.1-0.2 microg/g soil. In the third method, the recovery of fluroxypyr was determined by solid liquid extraction using an ultrasonic bath. The recovery of fluroxypyr at spiking levels of 4-50 microg/L ranged from 88 to 98% with relative standard deviations of 3.0-5.8% with a minimum detection limit of 4 microg/kg. In the fourth method, fluroxypyr was extracted using the solid liquid extraction method followed by the cleaning up step with OASIS HLB (polyvinyl dibenzene). The recovery of fluroxypyr was between 91 and 95% with relative standard deviations of 4.2-6.2%, respectively. The limit of detection in method 4 was further improved to 1 pg/kg. When the weight of soil used was increased 4 fold, the recovery of fluroxypyr at spiking level of 1-50 microg/kg ranged from 82-107% with relative standard deviations of 0.5-4.7%.
Three new 5,1'-coupled naphthylisoquinoline alkaloids, ancistrobenomine A (1), 6-O-demethylancistrobenomine A (2), and 5'-O-demethylancistrocline (3), have been isolated from the stem bark of a botanically as yet undescribed highland liana Ancistrocladus sp., proposed to be named "A. benomensis" according to the region in Peninsular Malaysia where it has been discovered on the mountain of Gunung Benom. Two of the compounds possess an unprecedented structure with a novel hydroxymethylene group at C-3 of the fully dehydrogenated isoquinoline moiety. The structural elucidation was achieved by chemical, spectroscopic, and chiroptical methods. As typical of the so-called Ancistrocladaceae type, all of the compounds isolated bear an oxygen at C-6. Biological activities of these alkaloids against different protozoic pathogens are described.
The Asian Society of Transplantation, founded in 1989 includes Indonesia, Japan, Korea, Malaysia, Oman, Pakistan, Republic of China, Philippines, Saudi Arabia, Singapore, Taiwan, Thailand, and the United Arab Emirates (UAE). The registry was also started from the same year in cooperation with these 16 countries. A questionnaire was sent to the key person of each country every year. The questionnaire includes (a) number of centers that performed organ transplants, (b) varieties and numbers of organ transplants performed in 2000 and 2001, (c) present status of dialysis, number of dialysis patients, and number of the candidates on the list for transplantation, (d) number of patients going abroad for transplantation, and (e) recent transplant highlights, news and issues affecting each country during 2000 and 2001. We previously gathered data for 2000, except for Indonesia, Singapore, and the UAE. Regarding 2001 data, we will send the questionnaires to the countries involved.
MeSH terms: Asia; Geography; Humans; Surveys and Questionnaires; Tissue Donors/statistics & numerical data; Organ Transplantation/trends*; Organ Transplantation/statistics & numerical data