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Biomedical subjects

K S Tan

Publications and source records attributed to K S Tan.

At least 19 recordsLinked to original sources

Paclitaxel, 5-fluorouracil and hydroxyurea concurrent with radiation in locally advanced nasopharyngeal carcinoma.

BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced nasopharyngeal carcinoma (NPC). We conducted a phase II trial using paclitaxel, 5-fluorouracil and hydroxyurea concurrent with radiation (TFHX). PATIENTS AND METHODS: Fifty-nine patients with locally advanced NPC were treated with CRT consisting of 4-day continuous infusions of paclitaxel (20 mg/m(2)/d) and 5-fluorouracil (600 mg/m(2)/d), and oral hydroxyurea 500 mg bid for nine doses, every 3 weeks concurrent with radiotherapy (RT). RT consisted of once daily 200cGy fractions 5 times per week to a total of 7000cGy. RESULTS: Complete response was seen in 86% and 71% of patients at 4 and 12 months after CRT. The median follow-up was 34 months. Twenty-three patients experienced relapse. Sixteen deaths occurred: 13 from progressive disease. Three-year overall survival and progression-free survival were 72% and 54% respectively, with locoregional and distant control rates of 83% and 64% at 3 years respectively. Grade 3 to 4 acute toxicities included oropharyngeal mucositis in 81% of patients treated, dermatitis in 63%, weight loss in 32%, and neutropenia in 22%. Neutropenic fever was seen in 14%. There were no treatment-related deaths from acute toxicity. CONCLUSIONS: TFHX is shown to be feasible in NPC. Non-cross resistant induction chemotherapy should be further studied with this regimen.

Adult↗

Prevalence of peripheral artery disease in urban high-risk Malaysian patients.

Atherosclerosis is a progressive, disseminated condition that affects all the vascular beds. Peripheral arterial disease (PAD), a manifestation of atherosclerosis, measured non-invasively in the legs by ankle-brachial index (ABI) is associated with increased cardiovascular morbidity and mortality. Though several studies in the western industrialised countries have shown that PAD is widely prevalent in the general older population at risk, not much data are available in the South East Asian developing countries. We have conducted an epidemiological survey on the prevalence of PAD in high-risk patients at an urban hospital in Malaysia. A total of 301 consecutive patients aged 32-90 years were recruited during their follow-up clinic visits for established cardiovascular disease, ischaemic stroke or diabetes mellitus > or = 5 years. All participants underwent ABI measurement and were subjected to the Edinburgh claudication questionnaire to assess leg symptoms. The prevalence of PAD in our high-risk population was 23%, of which only 27% were symptomatic with the classical intermittent claudication. All the patients with PAD were diagnosed at the time of the study. PAD was found in 33% of patients with pre-existent cardiovascular disease, 28% in patients with ischaemic stroke and 24% in diabetic patients. PAD was also highly prevalent among the younger patients. Our study has shown that PAD is highly prevalent among high-risk Malaysian patients and is not necessarily a disease of older age. Only 27% of these patients were symptomatic. All the subjects with PAD were diagnosed at the time of the study, which would suggest it is an unrecognised and underdiagnosed condition, even in patients with atherosclerotic risk factors.

Adult↗

Organotin and Irgarol-1051 contamination in Singapore coastal waters.

The seas surrounding Singapore are principally utilized by the shipping industry but are now also increasingly used for a variety of other purposes, including desalination for supplies of drinking water and intensive aquaculture of food fish. While stringent environmental pollution standards are in place for industrial effluents, there is currently no legislative control over pollution from anti-fouling paints in Singapore. In this study, the concentrations of toxic antifouling agents tributyltin (TBT), triphenyltin (TPhT) and Irgarol-1051 (2-methylthio-4-tert-butylamino-6-cyclopropylamino-s-triazine) were determined from seawater obtained from 26 locations along and off the coast of Singapore in October and November 2000. These compounds were isolated by liquid-liquid extraction derivatized under controlled microwave heating and quantified by gas chromatography-mass spectrometry. TBT concentrations in seawater ranged between 0.43 and 3.20 microg 1(-1) with a mean value of 1.40 +/- 0.60 micro 1(-1). The mean values of DBT and MBT were 1.07 +/- 0.80 microg 11(-1) and 0.34 +/- 0.50 microg 1(-1) respectively, while TPhT concentrations of up to 0.40 microg 1(-1) were found. Monophenyltin and diphenyltin were not detected in all samples analysed. Irgarol-1051 was found to be present at concentrations of between 3.02 microg 1(-1) and 4.20 microg 1(-1) in seawater with a mean value of 2.00 +/- 1.20 microg 1(-1).

Environmental Monitoring↗

Do Blastocystis hominis colony forms undergo programmed cell death?

Ultrastructural observations were made on colony forms of the protozoan parasite, Blastocystis hominis. Cross-sections of entire colonies were observed by TEM. Cells within a colony were heterogeneous in morphology, consisting of vacuolar, amoeboid, multivacuolar and unusual forms. Dying cells appeared to be in the process of fragmenting into numerous membranebound vesicles, giving rise to empty spaces within the colony. Interestingly, older colonies appeared to show cell fragmentation which resulted in larger, membranebound structures. Numerous cytoplasmic inclusions were present in the central vacuole of some cells, with many containing mitochondria. Amoeboid forms were observed to harbour small membrane-bound vesicles in endosome-like compartments. Other unusual features included margination of chromatin material and distinct blebbing of nuclei. These ultrastructural features suggest that B. hominis colony forms perhaps undergo a form of programmed cell death.

Animals↗

Exposure of Blastocystis species to a cytotoxic monoclonal antibody.

A recently described cytotoxic monoclonal antibody (mAb 1D5) raised against Blastocystis hominis isolate B, was tested for reactivity with 13 different isolates of Blastocystis. The isolates used were previously isolated from humans, rats and reptiles and were maintained as axenised cultures throughout the course of this study. Five B. hominis isolates (B, C, E, G and H) were found to react with mAb 1D5 in immunoblotting studies and the indirect fluorescence antibody test. The pattern of fluorescence observed for all five isolates was diffuse and patchy. Immunoblotting studies revealed that mAb 1D5 reacted with a 29-30-kDa protein found in all five isolates. Results of a cytotoxic assay showed that the mAb exhibited a complement-independent cytotoxic effect on all the exposed isolates. Microscopic observations showed differences in morphology between the Blastocystis cells exposed and unexposed to mAb. Acridine orange staining performed on both exposed and unexposed cells showed similar internal structures when viewed under fluorescence microscopy.

Animals↗

Blastocystis hominis: evidence for caspase-3-like activity in cells undergoing programmed cell death.

We have shown previously that the human intestinal protozoan, Blastocystis hominis, undergoes apoptosis-like programmed cell death (PCD) when exposed to a cytotoxic monoclonal antibody (mAb), 1D5. In the present study, ELISA and immunoblot assays employing chicken anti-CPP32 antibody suggest that caspase-3-like antigens exist in B. hominis. Using colorimetric and flow cytometric assays for caspase-3 activity, we also observed an increase in activity between 1 h and 6 h after exposure to mAb 1D5, with greatest activity at 6 h. These findings suggest that caspase-3-like proteases play an important role in B. hominis undergoing PCD, similar to the phenomenon in higher eukaryotic organisms.

Animals↗

Programmed cell death in a human intestinal parasite, Blastocystis hominis.

Although programmed cell death (PCD) has been associated with multicellular organisms, there have been more reports of its presence in some protozoans. Our study shows the existence of PCD in an intestinal protozoan, Blastocystis hominis. Light and electron microscopy, biochemical and flow cytometry studies showed apoptosis-like death in B. hominis cells exposed to a cytotoxic monoclonal antibody (MAb 1D5). B. hominis cells displayed key morphological and biochemical features of apoptosis, namely, nuclear condensation and in situ fragmentation, reduced cytoplasmic volume, some externalization of phosphatidylserine and maintenance of plasma membrane integrity. No oligonucleosomal DNA laddering was observed in gel electrophoresis. This study supports earlier observations that the cellular machinery that is required to carry out PCD may have existed before the advent of multicellularity. Our study also ascribes a novel function for the B. hominis central vacuole in apoptosis; it acts as a repository where apoptotic bodies are stored before being released into the extracellular space.

Animals↗

Prevalence of Actinobacillus actinomycetemcomitans in an ethnic adult Chinese population.

AIM: The aim of this study was to determine the prevalence and the structure of the leukotoxin promoter region of Actinobacillus actinomycetemcomitans in an ethnic Chinese population. METHOD: Subgingival plaque samples were collected from 42 patients with moderate to advanced periodontitis and 50 periodontally healthy patients. A. actinomycetemcomitans was detected directly from the crude subgingival plaque by PCR using leukotoxin gene specific primers. The presence of A. actinomycetemcomitans was determined by a single 285 bp PCR amplicon. RESULTS: A. actinomycetemcomitans was found to be present in the subgingival plaque of 68 out of a total of 92 patients examined (74%). 29 out of the 42 periodontitis patients tested were carriers of A. actinomycetemcomitans (69%). Among the periodontally healthy patients studied, 39 out of 50 subjects possessed the bacteria (78%). PCR analysis of the promoter region of the ltx operon revealed that none of the 42 moderate to advanced periodontitis patients examined harboured A. actinomycetemcomitans strains with the JP2-like promoter of the ltx operon, known to enhance leukotoxin expression. 2 out of the 27 advanced periodontitis patients clinically diagnosed as suffering from rapidly progressive periodontitis were found to be carriers of the mildly toxic strain of A. actinomycetemcomitans with the characteristic 652-like promoter. CONCLUSIONS: The high prevalence of A. actinomycetemcomitans, regardless of whether the subgingival samples were analysed from patients with healthy or diseased periodontium suggests that this bacterial species is part of the normal oral flora of ethnic Chinese. Our preliminary results also suggested that subjects who harboured the mildly toxic strain of A. actinomycetemcomitans were potentially susceptible to aggressive forms of periodontitis.

Actinobacillus Infections↗

Bacteroides forsythus prtH genotype in periodontitis patients: occurrence and association with periodontal disease.

Bacteroides forsythus has been described as a periodontopathogen and its presence in the subgingival plaque can lead to periodontal disease. Recently, a cysteine protease designated as prtH was isolated and characterized from B. forsythus ATCC 43037. The purpose of this study was to determine the prevalence and the association of the prtH gene of B. forsythus with periodontal disease. A total of 160 subgingival plaque samples were assayed with the polymerase chain reaction method using oligonucleotide primers targeting the prtH and the 16S rDNA genes of B. forsythus. Primers targeting the 16S rDNA gene of B. forsythus were used to determine the occurrence of the bacteria in the subgingival plaque samples at baseline. At baseline, B. forsythus was detected in 78 out of 86 (91%) diseased sites and 33 out of 74 (45%) healthy sites studied. Among the 86 diseased sites examined, 73 sites (85%) were colonized by the bacteria with the prtH genotype. In sites of the periodontally healthy, 7 out of 73 (10%) possessed B. forsythus with the prtH genotype. The results obtained suggested strong association of the prtH gene of B. forsythus with adult periodontitis. Although this bacterial species was detected from about half of the periodontally healthy samples, only a fraction of these subjects possess the bacteria strain with the prtH genetic subtype. We propose the use of the prtH gene as an alternative to the more widely used 16S rDNA gene of B. forsythus, for a more accurate determination of the prevalence of periodontal health and disease in epidemiological studies and clinical screening.

Adult↗

Description of a new species of Thais (Mollusca: Neogastropoda: Muricidae) from Taiwan, based on morphological and allozyme analyses.

Thais keluo sp. nov. is described from intertidal shores of southwest Taiwan. The new species is differentiated from five other closely related species, namely T. bitubercularis (Lamarck), T. jubilaea Tan and Sigurdsson, T. clavigera (Küster), T. luteostoma (Holten) and T. rufotincta Tan and Sigurdsson, all of which occur in the South China Sea, on the basis of shell, radula and penis morphology. Thais keluo is also distinguished from the latter three species based on allozyme electrophoresis. The shell of T. keluo is characterized by four raised, spiral bands on the last whorl, one or two small, oblique columellar plica(e) on the inner lip, a finely crenate, thin, narrow, reddish-brown outer lip edge and four white, papillate denticles inside the outer lip of the aperture. In males, the penis is curved with a long, simple flagellum. The UPGMA cluster analysis based on 9 enzyme loci revealed that T. luteostoma is more closely related to T. clavigera than to T. keluo n.sp. The Nei's genetic distance (D) obtained between the new species and T. clavigera/T. luteostoma was 0.31, while T. clavigera and T. luteostoma were separated by a distance of 0.16. Thais rufotincta was separated from the other species by a distance of 0.78. In contrast, phylogenetic analysis of morphological data by maximum parsimony suggested that T. luteostoma was more closely related to T. keluo than to T. clavigera. However, both analyses indicated the close relationship amongst T. clavigera, T. luteostoma and the new species in relation to T. rufotincta.

Animals↗

Premenstrual asthma: epidemiology, pathogenesis and treatment.

The exacerbation of asthma in the premenstrual period has long been of interest. Premenstrual asthma has been estimated to affect up to 40% of females with asthma, although the exact prevalence of this phenomenon is unclear as studies have involved small numbers in hospital clinics. Large-scale community-based studies are required to estimate its true prevalence. Researchers are slowly piecing together clues as to the aetiology and pathogenesis of the disorder. Female sex-steroid hormones play an important role but the exact mechanism is still unknown. Recent evidence suggests that increased airway hyperresponsiveness, an indicator of underlying airway inflammation, during the luteal phase of the menstrual cycle may account for premenstrual exacerbations. In addition, there is now evidence of impaired or altered beta2-adrenoceptor function and regulation in females with asthma, which may have a part to play. Accurate diagnosis is dependent on a detailed history and the demonstration of premenstrual dip in peak expiratory flow. Exacerbations in the majority of women will respond to the usual treatment of bronchial asthma. However, a few women will experience significant morbidity or treatment-related adverse effects. Case reports suggest that the combined oral contraceptive pill or gonadotrophin-releasing hormone analogues may be effective in these patients. This requires substantiation by randomised controlled trials.

Adolescent↗

Asthma in pregnancy.

Although about 1% of pregnant women have asthma, it is often underrecognized and suboptimally treated. The course of asthma during pregnancy varies; it improves, remains stable, or worsens in similar proportions of women. The risk of an asthma exacerbation is high immediately postpartum, but the severity of asthma usually returns to the preconception level after delivery and often follows a similar course during subsequent pregnancies. Changes in beta(2)-adrenoceptor responsiveness and changes in airway inflammation induced by high levels of circulating progesterone have been proposed as possible explanations for the effects of pregnancy on asthma. Good control of asthma is essential for maternal and fetal well-being. Acute asthmatic attacks can result in dangerously low fetal oxygenation. Chronically poor control is associated with pregnancy-induced hypertension, preeclampsia, and uterine hemorrhage, as well as greater rates of cesarian section, preterm delivery, intrauterine growth retardation, low birth weight, and congenital malformation. Women with well-controlled asthma during pregnancy, however, have outcomes as good as those in their nonasthmatic counterparts. Inhaled therapies remain the cornerstone of treatment; most appear to be safe in pregnancy.

Adrenergic beta-Agonists↗

Blastocystis hominis: A simplified, high-efficiency method for clonal growth on solid agar.

Colony growth of protozoan parasites in agar can be useful for axenization, cloning, and viability studies. This is usually achieved with the pour plate method, for which the parasite colonies are situated within the agar. This technique has been described for Giardia intestinalis, Trichomonas vaginalis, and Entamoeba and Blastocystis species. Extracting such colonies can be laborious. It would be especially useful if parasites could be grown on agar as colonies. These colonies, being exposed on the agar surface, could be conveniently isolated for further investigation. In this study, we report the successful culture of B. hominis cells as colonies on solid agar. Colonies were enumerated and the efficiency of plating was determined. It was observed that B. hominis could be easily cultured on agar as clones. The colonies were dome-shaped and mucoid and could grow to 3 mm in diameter. Flow cytometric analyses revealed that parasite colonies remained viable for up to 2 weeks. Viable colonies were conveniently expanded in liquid or solid media. Scanning electron microscopy revealed that each colony consists of two regions; a dome-shaped, central core region and a flattened, peripheral region. Older colonies possessed numerous strand-like surface coat projections. This study provides the first report of clonal growth of B. hominis on agar and a simple, effective method for cloning and expansion of B. hominis cells.

Agar↗

High mortality in Nipah encephalitis is associated with presence of virus in cerebrospinal fluid.

During the outbreak of Nipah virus encephalitis in Malaysia, stored cerebrospinal fluid (CSF) samples from 84 patients (27 fatal and 57 nonfatal cases) were cultured for the virus. The virus was isolated from 17 fatal cases and 1 nonfatal case. There were significant associations between CSF virus isolation and mortality as well as clinical features associated with poor prognosis. In addition, there was a positive linear correlation of CSF virus isolation with age. There was no significant association between CSF virus isolation and the character of the CSF, presence of Nipah-specific antibody in the serum or CSF, duration of illness before collection of samples, or sex or ethnicity of the patients. This study suggests that high viral replication in the central nervous system may be an important factor for high mortality.

Adolescent↗

Colony growth as a step towards axenization of Blastocystis isolates.

Colonies of Blastocystis from non-axenic cultures grown in agar medium were isolated from bacterial colonies. Axenization of human and reptilian isolates of Blastocystis was achieved using antibiotic treatment to lower bacterial numbers, followed by colony growth to isolate pure parasite colonies.

Animals↗

Terrestrial gamma ray dose rates of Brunei Darussalam.

GPS-indexed in-situ and car-borne survey of terrestrial gamma-ray dose rates were carried out in Brunei and adjacent areas using two portable NaI(Tl) counters. The mean and population weighted average dose rates for Brunei are 34 and 33 nGy/h, respectively. The car-borne data and the in-situ data when spectral analysed separately, were found to show fractal behaviour with D of 1.7 and 1.8, respectively. A contour map of the dose rates was also produced.

Air Pollutants, Radioactive↗