Internet search has been the main source for information and data mining in medical research. Its use by medical students has immensely contributed to learning activities. The main aim of the study was to determine the effectiveness of internet use by medical students during their initial years of clinical instruction in order to establish a diagnosis after being provided with the history and physical findings of a clinical problem.
A total of 25 alkaloids were isolated from the leaf and stem-bark extracts of Alstonia spatulata, of which five are new alkaloids of the strychnan type (alstolucines A-E, 1-5) and the other, a new alkaloid of the secoangustilobine A type (alstolobine A, 6). The structures of these alkaloids were established using NMR and MS analysis and, in the case of alstolucine B (2), also confirmed by X-ray diffraction analysis. A reinvestigation of the stereochemical assignment of scholaricine (13) by NMR and X-ray analyses indicated that the configuration at C-20 required revision. Alkaloids 1, 2, 6, 7, 9, 10, and 13 reversed multidrug resistance in vincristine-resistant KB cells.
Our objective was to determine the survival and prognostic factors of motor neuron disease (MND) in a multi-ethnic cohort of Malaysian patients. All patients seen at a university medical centre between January 2000 and December 2009 had their case records reviewed for demographic, clinical and follow-up data. Mortality data, if unavailable from records, were obtained by telephone interview of relatives or from the national mortality registry. Of the 73 patients, 64.4% were Chinese, 19.2% Malays and 16.4% Indians. Male: female ratio was 1.43: 1. Mean age at onset was 51.5 + 11.3 years. Onset was spinal in 75.3% and bulbar in 24.7% of the patients; 94.5% were ALS and 5.5% were progressive muscular atrophy (PMA). Overall median survival was 44.9 + 5.8 months. Ethnic Indians had shorter interval from symptom onset to diagnosis and shorter median survival compared to non-Indians. On Cox proportional hazards analysis, poor prognostic factors were bulbar onset, shorter interval from symptom onset to diagnosis and worse functional score at presentation. In conclusion, age of onset and median survival duration are similar to previous reports in Asians. Clinical features and prognostic factors are similar to other populations. In our cohort, ethnic Indians had more rapid disease course accounting for their shorter survival.
Five local Malaysian patients with clinical manifestations consistent with lymphatic filariasis were referred to our medical centre between 2003 and 2006. Although no microfilariae (mf) were detected in their nocturnal blood samples, all were diagnosed to have lymphatic filariasis on the basis of clinical findings and positive serology results. PCR on their blood samples revealed that two of the patients were infected with Brugia pahangi, an animal filarial worm hitherto not known to cause human disease in the natural environment. All the patients were successfully treated with anti-filarial drugs: four patients were treated with a combination of diethylcarbamazine (DEC) and albendazole, and one with doxycycline. Four of them were residents of Petaling Jaya, a residential suburbia located 10 km southwest of Kuala Lumpur city, Malaysia. The fifth patient was a frequent visitor of the suburbia. This suburbia has no history or record of B. malayi infection. The most likely vector of the worm was Armigeres subalbatus as extensive entomological surveys within the suburbia revealed only adult females of this mosquito species were infected with B. pahangi larvae. Wild monkeys caught in the suburbia were free from B. pahangi mf, but domestic cats were mf positive. This suggests that infected cats might be the source of the zoonotic infection in the suburbia.
MSCs (mesenchymal stem cells) promise a great potential for regenerative medicine due to their unique properties of self-renewal, high plasticity, modulation of immune response and the flexibility for genetic modification. Therefore, the increasing demand for cellular therapy necessitates a larger-scale production of MSC; however, the technical and ethical issues had put a halt on it. To date, studies have shown that MSC could be derived from human UC (umbilical cord), which is once considered as clinical waste. We have compared the two conventional methods which are classic enzymatic digestion and explant method with our newly tailored enzymatic-mechanical disassociation method to generate UC-MSC. The generated UC-MSCs from the methods above were characterized based on their immunophenotyping, early embryonic transcription factors expression and mesodermal differentiation ability. Our results show that enzymatic-mechanical disassociation method increase the initial nucleated cell yield greatly (approximately 160-fold) and maximized the successful rate of UC-MSC generation. Enzymatic-mechanical disassociation-derived UC-MSC exhibited fibroblastic morphology and surface markers expression of CD105, CD73, CD29, CD90 and MHC class I. Furthermore, these cells constitutively express early embryonic transcription factors (Nanog, Oct-4, Sox-2 and Rex-1), as confirmed by RT-PCR, indicating their multipotency and high self-renewal capacity. They are also capable of differentiating into osteoblasts and adipocytes when given an appropriate induction. The present study demonstrates a new and efficient approach in generating MSC from UC, hence serving as ideal alternative source of mesenchymal stem cell for clinical and research use.
The range-gated imaging systems are reliable underwater imaging system with the capability to minimize backscattering effect from turbid media. The tail-gating technique has been developed to fine tune the signal to backscattering ratio and hence improve the gated image quality. However, the tail-gating technique has limited image quality enhancement in high turbidity levels. In this paper, we developed a numerical model of range-gated underwater imaging system for near target in turbid medium. The simulation results matched the experimental work favorably. Further investigation using this numerical model shows that the multiple scattering components of the backscattering noise dominate for propagation length larger than 4.2 Attenuation Length (AL). This has limited the enhancement of tail-gating technique in high turbidity conditions.
Serum deprivation inhibits cell growth and initiates apoptosis cell death in mammalian cell cultures. Since apoptosis is a genetically controlled cell death pathway, over-expression of anti-apoptotic proteins may provide a way to delay apoptosis. This study investigated the ability of the X-linked inhibitor of apoptosis protein (XIAP) to inhibit apoptosis induced by serum deprivation. Study includes evaluation of the ability of XIAP to prolong culture period and its effect on cell proliferation in serum-deprived media. The full length human XIAP was introduced into CHO-K1 cell lines and the effects of XIAP over-expression on the inhibition of apoptosis induced by serum-deprived conditions were examined. In batch cultures, cells over-expressing XIAP showed decreased levels of apoptosis and a higher number of viable cell under serum-deprived conditions compared to the control cell lines. The viability of control cells dropped to 40% after 2days of serum deprivation, the XIAP expressing cells still maintained at a viability higher than 90%. Further investigation revealed that the caspase-3 activity of the CHO-K1 cell line was inhibited as a result of XIAP expression.
Nine species of mosquitoes in eight genera are recorded for the first time in Singapore. An additional two species were overlooked in a 1986 checklist for mosquitoes in Singapore, and one was described after 1986. Location and habitat data are provided for the nine new records. With the inclusion of these new records the number of species reported from Singapore is 137.
Cervical cancer is the second most common cancer affecting Malaysian women. Despite the implementation of pap smear screening, many women are still diagnosed only in the advanced stage of cervical cancer. This could partly be due to failure of detection of its precursor lesions; hence the need to search for novel biomarkers to assist in the screening and diagnosis of cervical neoplasia. This study aims to determine the expression of p16INK4A and survivin as possible predictive biomarkers in cervical squamous neoplasm.
Variation in CYP2A6 levels and activity can be attributed to genetic polymorphism and, thus, functional characterization of allelic variants is necessary to define the importance of CYP2A6 polymorphism in humans. The aim of the present study was to investigate the reported alleles CYP2A6*15, CYP2A6*16, CYP2A6*21, and CYP2A6*22, in terms of the functional consequences of their mutations on the enzyme catalytic activity. With use of the wild-type CYP2A6 cDNA as template, site-directed mutagenesis was performed to introduce nucleotide changes encoding K194E substitution in CYP2A6*15, R203S substitution in CYP2A6*16, K476R substitution in CYP2A6*21, and concurrent D158E and L160I substitutions in CYP2A6*22. Upon sequence verification, the CYP2A6 wild-type and mutant constructs were individually coexpressed with NADPH-cytochrome P450 reductase in Escherichia coli. A kinetic study using a coumarin 7-hydroxylase assay indicated that CYP2A6*15 exhibited higher V(max) than the wild type, whereas all mutant constructs, except for variant CYP2A6*16, exhibited higher K(m) values. Analysis of the V(max)/K(m) ratio revealed that all mutants demonstrated 0.85- to 1.05-fold differences from the wild type, with the exception of variant CYP2A6*22, which only portrayed 39% of the wild-type intrinsic clearance. These data suggested that individuals carrying the CYP2A6*22 allele are likely to have lower metabolism of CYP2A6 substrate than individuals expressing CYP2A6*15, CYP2A6*16, CYP2A6*21, and the wild type.
The distributions of Cu, Zn, and Pb concentrations in the selected soft tissues (foot, cephalic tentacle, mantle, muscle, gill, digestive caecum, and remaining soft tissues) and shells of the mud-flat snail Telescopium telescopium were determined in snails from eight geographical sites in the south-western intertidal area of Peninsular Malaysia. Generally, the digestive caecum compared with other selected soft tissues, accumulated higher concentration of Zn (214.35+/-14.56 microg/g dry weight), indicating that the digestive caecum has higher affinity for the essential Zn to bind to metallothionein. The shell demonstrated higher concentrations of Pb (41.23+/-1.20 microg/g dry weight) when compared to the selected soft tissues except gill from Kuala Sg. Ayam (95.76+/-5.32 microg/g dry weight). The use of different soft tissues also can solve the problem of defecation to reduce error in interpreting the bioavailability of heavy metals in the intertidal area.
A 3-year-old girl with facial dysmorphic features suggestive of Cornelia de Lange syndrome was seen in the ophthalmology unit for a right leukocoria. The leukocoria was found to be caused by a large retinoblastoma and the right eye was enucleated. Chromosomal analysis revealed partial chromosome 13q deletion involving band 14 which is associated with a high risk of retinoblastoma. This case shows that patient with chromosome 13q deletion syndrome cannot be diagnosed based on dysmorphic features only. Chromosomal analysis is warranted in all infants with facial dysmorphism suggestive of Cornelia de Lange syndrome so that those with chromosome 13q deletion can be referred early for early detection of retinoblastoma.
HBcAg (hepatitis B core antigen) is a nanoplex bioproduct that has a great potential in the development of therapeutic drugs and vaccines. In the present study, a continuous-flow bead milling for the disruption of Escherichia coli was optimized and a direct recovery protocol to isolate the recombinant HBcAg from the unclarified E. coli disruptate was developed. The optimal condition for continuous-flow bead milling for the release of HBcAg from E. coli was achieved at a feed flow rate of 15 litres/h, biomass concentration of 10% [ww/v (wet weight/vol.)] and impeller tip speed of 14 m/s. The sucrose-density-gradient analysis showed that the particulate form of the HBcAg released by this optimal condition is still preserved. In the direct purification of HBcAg from the unclarified disruptate, the AE-EBAC (anion-exchange expanded-bed adsorption chromatography) technique was employed. A 54% adsorption and 50.7% recovery of HBcAg were achieved in this direct recovery process. The purity of HBcAg recovered was 49.8%, which corresponds to a purification factor of 2.0. ELISA showed that the HBcAg recovered is functionally active.
A bioequivalence study of two oral formulations of 500 mg tablets of ciprofloxacin (RAZA Pharmaniaga, Malaysia) as test and Ciprobay (Bayer AG, Germany) as reference, was carried out in 24 healthy human volunteers. Each volunteer received a single dose of ciprofloxacin.
The aim of the present study was to investigate the association of C4 gene mutations with systemic lupus erythematosus, in 130 Malaysian SLE patients and 130 healthy controls. Generally, various PCR approaches were used to screen the mutations of the C4 genes, which included 2 bp (+TC) insertions at codon 1213 in exon 29, 1 bp deletions (-C) at codon 811 in exon 20, 1 bp (-C), 2 bp (-GT) deletions at codons 522 and 497 in exon 13 and null alleles. No mutations located at exons 13, 20 and 29 of the C4 gene, were detected amongst the patient and control samples in this study. C4A*Q0 was found in two out of the 130 control samples, while C4B*Q0 was present in two out of the 130 SLE patients. Overall, our results do not demonstrate a significant association to these known C4 mutations identified by previous studies, in the Malaysian scenario.
The human concentrative nucleoside transporter (hCNT2), also known as SLC28A2, plays an important role in the cellular uptake across intestinal membrane of some naturally occurring nucleosides and nucleoside analogs. This study aims to determine the genetic variability of hCNT2 (SLC28A2) in three major Asian ethnic groups residing in Singapore: Chinese, Malay and Indian, and functionally characterize the variants of hCNT2. Healthy participants (n=96) from each group were screened for genetic variations in the exons of hCNT2 (SLC28A2) using denaturing high performance liquid chromatography and sequencing analyses. A total of 23 polymorphisms were identified in the exonic and flanking intronic regions, and ethnic differences in single nucleotide polymorphism frequencies were evident. Five novel nonsynonymous variants (L12R, R142H, E172D, E385K, M612T) were constructed by mutagenesis and functionally characterized in U-251 cells. Expression of these variants in U-251 cells revealed that all except E385K can uptake various substrates of hCNT2: inosine, ribavirin and uridine.
Ectopic pregnancy is conventionally managed by laparoscopic salpingectomy. Electrocautery has been used widely to secure hemostasis during salpingectomy. However, this method is associated with a risk of thermal injury to the visceral organs. Endoloop, a pre-tied suture used in laparoscopic surgery may be an alternative treatment tool and its potential use in the management of ectopic pregnancy is explored here. Our study aims to compare the effectiveness of the endoloop technique to electrocautery during laparoscopic salpingectomy for tubal pregnancy.
Infection is a relatively rare but devastating complication of intracardiac device implantation. Burkholderia pseudomallei is the organism which causes melioidosis, an endemic and lethal infection in the tropics. We describe a case of pacemaker infection secondary to Burkholderia pseudomallei, which was treated by explantation of the device and appropriate antimicrobial therapy.
Direct recovery of hepatitis B core antigen (HBcAg) from unclarified Escherichia coli homogenates via expanded bed adsorption chromatography (EBA) has been explored in this study. Streamline DEAE was selected as the anion exchanger to recover HBcAg from heat-treated and non-heat-treated unclarified feedstocks. The use of anion-exchanger for direct extraction of proteins from unclarified feedstock is not preferred due to lack of specificity of its ligand. In this study, thermal treatment of the unclarified feedstock at 60 degrees C has resulted in 1.2- and 1.8-fold increases in yield and purity of HBcAg, respectively, compared with that purified from non-heat-treated feedstock. Heating the crude feedstock has resulted in denaturation and precipitation of contaminants in the feedstock, hence reducing non-specific interactions between the cell debris and adsorbent. The selectivity of the anion-exchanger has also been increased as shown in the breakthrough curve obtained. Enzyme-linked immunosorbent assay showed that the antigenicity of the HBcAg from heat-treated unclarified feedstock is still preserved.
This study was focused on investigating the optimum fluidising velocity during the combustion of rice husk in a bench-scale fluidised bed combustor (ID 210mm) to obtain low carbon ash in the amorphous form. When all other parameters are held constant, the optimum fluidizing velocity aids in almost complete combustion, thereby releasing the entrapped carbon for further conversion. This results in ash with consistently low carbon content (less than 2wt%). The range of fluidising velocities investigated was from as low as 1.5U(mf) to as high as 8U(mf). It was found that the optimum fluidising velocity was approximately 3.3U(mf) as the mixing of rice husk with the bed was good with a high degree of penetration into the sand bed. The resulting ash retained its amorphous form with low residual carbon content (at 2.88wt%) and minimal sand contamination as shown by the X-ray diffraction analysis.