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Biomedical subjects

W C Tan

Publications and source records attributed to W C Tan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Dietary isothiocyanates, glutathione S-transferase -M1, -T1 polymorphisms and lung cancer risk among Chinese women in Singapore.

Chinese populations consume a diet relatively high in isothiocyanates (ITCs), a derivative of cruciferous vegetables known to have cancer-protective effects. This class of compounds is metabolized by the glutathione S-transferase family of enzymes, which are also involved in the detoxification of tobacco-related carcinogens such as polycyclic aromatic hydrocarbons and alkyl halides. We evaluated the association between dietary isothiocyanate intake, GSTM1 and GSTT1 polymorphisms, and lung cancer risk in 420 Chinese women: 233 histologically confirmed lung cancer patients and 187 hospital controls. Among these, 58.8% of cases and 90.3% of controls were lifetime nonsmokers. An allele-specific PCR method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in DNA isolated from peripheral blood. Higher weekly intake of ITCs (above the control median value of 53.0 micromol) reduced the risk of lung cancer to a greater extent in smokers [adjusted odds ratio (OR), 0.31; 95% confidence interval (CI), 0.10-0.98] than nonsmokers (OR, 0.70; 95% CI, 0.45-1.11). The inverse association was stronger among subjects with homozygous deletion of GSTM1 and/or GSTT1. Among nonsmokers with GSTM1-null genotype, higher intake of ITCs significantly reduced the risk of lung cancer (OR, 0.54; 95% CI, 0.30-0.95), an effect not seen among those with detectable GSTM1 (OR, 1.07; 95% CI, 0.50-2.29). Our results, in a Chinese female population, are consistent with the hypothesis that ITC is inversely related to the risk of lung cancer, and we show that among nonsmokers this effect may be primarily confined to GST-null individuals. Conjugation and elimination of ITCs is enhanced in GST-non-null relative to -null individuals, such that the GST metabolic genotype modifies the protective effect of ITCs on lung cancer development.

Adult↗
PubMed2000

Polymorphisms in the IL4, IL4RA, and FCERIB genes and asthma severity.

BACKGROUND: Genetic polymorphisms have been associated with asthma and asthma severity. OBJECTIVE: We sought to determine whether 3 polymorphisms were associated with severe asthma indicated either by the occurrence of a fatal (or near-fatal) asthma attack or by severe airflow obstruction. METHODS: We obtained DNA and clinical data from asthmatic subjects who either died or nearly died during an asthma attack and from a group of subjects with mild-to-moderate asthma who had never experienced a fatal or near-fatal asthma episode. These groups were compared with a group of nonatopic nonasthmatic control subjects. The level of airflow obstruction (FEV(1) percent predicted) in the subjects with mild-to-moderate asthma was used as an additional measure of disease severity. The subjects were genotyped for the IL4*C-589T promoter polymorphism and the IL4RA*Q576R and the FCERIB*E237G amino acid substitutions. RESULTS: The results showed that the FCERIB*E237G and IL4RA*Q576R polymorphisms were not associated with fatal or near-fatal asthma. However, the IL4*-589T allele was significantly increased in the subjects with fatal or near-fatal asthma compared with nonasthmatic subjects (odds ratio [OR], 1.8; P =.02) and subjects with mild-to-moderate asthma (OR, 1.9; P =.02). There was no interaction between the IL4*-589T and IL4RA*576R alleles. Of the 3 polymorphisms, only the IL4RA*576R allele was associated with severe airflow obstruction (OR, 8.2; P =.01). CONCLUSION: These data suggest that the IL4*-589T allele is a risk factor for life-threatening asthma and that the IL4RA*576R allele is a risk factor for a low level of lung function in asthmatic subjects.

Airway Obstruction↗
PubMed2000

The human bone marrow response to acute air pollution caused by forest fires.

Atmospheric pollution increases cardiopulmonary morbidity and mortality by unexplained mechanisms. Phagocytosis of fine particles (PM(10)) by rabbit alveolar macrophages elevates white blood cells (WBC) by releasing precursors from the bone marrow and this could contribute to the pathogenesis of cardiopulmonary disease. The present study examined the association between acute air pollution caused by biomass burning and peripheral WBC counts in humans. Serial measurements of the WBC count made during the 1997 Southeast Asian Smoke-haze (Sep 29, Oct 27) were compared with a period after the haze cleared (Nov 21, Dec 5) using peripheral blood PMN band cells to monitor marrow release. The results showed that indices of atmospheric pollution were significantly associated with elevated band neutrophil counts expressed as a percentage of total polymorphonuclear leukocytes (PMN), with maximal association on zero and 1 lag day for PM(10) and 3, and 4 lag days for SO(2) (p value < 0.000). We conclude that atmospheric pollution caused by biomass burning is associated with elevated circulating band cell counts in humans because of the increased release of PMN precursors from the marrow. We speculate that this response contributes to the pathogenesis of the cardiorespiratory morbidity associated with acute air pollution.

Adult↗
PubMed2000

Fumes from meat cooking and lung cancer risk in Chinese women.

Chinese women are recognized to have a high incidence of lung cancer despite a low smoking prevalence. Several studies have implicated domestic exposure to cooking fumes as a possible risk factor, although the exact carcinogens have yet to be identified. Heterocyclic amines are known carcinogens, which have been identified in cooked meat, and also in fumes generated during frying or grilling of meats. We conducted a case-control study of 303 Chinese women with pathologically confirmed, primary carcinomas of the lung and 765 controls to examine the association between exposure to meat cooking and lung cancer risk. Data on demographic background, smoking status, and domestic cooking exposure, including stir-frying of meat, were obtained by in-person interview while in hospital. The response rates among eligible cases and controls were 95.0 and 96.9%, respectively. The proportion of smokers (current or ex-smokers) among cases and controls was 41.7 and 13.1%, respectively. Adenocarcinomas comprised 31.5% of cancers among smokers and 71.6% among nonsmokers. When cases were compared with controls, the odds ratio (OR) for lung cancer (all subtypes) among ex-smokers was 4.3 [95% confidence interval (CI) 2.7-6.8] and that among current smokers was 5.0 (95% CI, 3.4-7.3). Among smokers, women who reported that they stir-fried daily in the past had a significantly increased risk of lung cancer (adjusted OR, 2.0; 95% CI, 1.0-3.8) and among these women, risk was enhanced for those who stir-fried meat daily (OR, 2.7; 95% CI, 1.3-5.5). Women who stir-fried daily but cooked meat less often than daily did not show an elevated risk (OR, 1.0. 95% CI, 0.5-2.4). Risk was further increased among women stir-frying meat daily who reported that their kitchen was filled with oily fumes during cooking (OR, 3.7; 95% CI, 1.8-7.5). These cooking practices on their own did not increase risk among nonsmokers in our study population. Our results suggest that inhalation of carcinogens, such as heterocyclic amines generated during frying of meat, may increase the risk of lung cancer among smokers. Further studies in different settings are warranted to examine this possibility, which may also help to explain the higher risk observed among women smokers compared with men.

Adenocarcinoma↗
PubMed1999

Dithiothreitol has a dose-response effect on cell surface antigen expression.

BACKGROUND: The use of Dithiothreitol (DTT) to improve cell dispersion is an integral step in induced sputum examination, which has become an important noninvasive method of assessing airway inflammation. Several studies have shown that sputum treatment with DTT does not affect cell morphology, differential cell counts, and cytokine levels in the supernatant. However, the effect of DTT on cell surface marker expression has not been systematically studied. OBJECTIVE: We have investigated the effect of different DTT concentrations on antigen expression on peripheral blood cells compared with antigen expression on PBS-treated cells. METHODS: Peripheral blood from different healthy donors was incubated with either DTT or PBS, washed, and then incubated with different fluorescence-labeled antibodies. Analysis was performed after lysis of erythrocytes on a calibrated flow cytometer. Respective cell populations were identified, and the mean fluorescence intensity of surface-marker expression for each cell population was compared between DTT- and PBS-treated cells. RESULTS: We found that DTT decreased the expression of CD11a and CD49d on lymphocytes and eosinophils. The expression of CD11a on neutrophils was also decreased after DTT treatment. DTT increased CD11b expression on lymphocytes, neutrophils, and eosinophils. DTT might also have a mild effect on cell activation. It decreased the expression of CD2 on lymphocytes and variably affected the expression of EG2 in eosinophils, although it had no significant effect on HLA-DR expression on lymphocytes. CONCLUSION: Our findings show that DTT can affect antigen expression on lymphocytes, neutrophils, and eosinophils and suggest the need for further investigation of similar consequences on induced sputum analysis.

Antigens, Surface↗
PubMed1999

Detection of Mycobacterium tuberculosis DNA using polymerase chain reaction in cutaneous tuberculosis and tuberculids.

BACKGROUND: The objective of this study was to explore the role of the polymerase chain reaction (PCR) fo the detection of Mycobacterium tuberculosis DNA as a diagnostic aid in cutaneous tuberculosis using routinely processed skin biopsy specimens. METHODS AND RESULTS: A wide range of clinical specimens representing different forms of cutaneous tuberculosis and so-called tuberculids were studied. A sensitive and specific PCR assay targeting the sequence IS6110 of Mycobacterium tuberculosis complex was used. The specimens were categorized as follows. 1 Acid-fast bacilli (AFB) positive on biopsy (nine specimens from seven patients who were immunocompromised). PCR was positive in five specimens. Of these, one specimen was culture positive and three specimens were culture negative. 2 AFB negative on biopsy: (a) tuberculosis verrucosa cutis (23 specimens); (b) lupus vulgaris (three specimens); (c) cutaneous tuberculosis clinically suspected (six specimens). PCR was negative in all specimens. 3 Tuberculids.' (a) erythema induratum/nodular vasculitis (20 specimens); (b) papulonecrotic tuberculid (two specimens); (c) erythema nodosum (20 specimens). PCR was negative in all specimens. CONCLUSIONS: The role of PCR in clinical dermatologic practice, at this stage, may be in differentiating between cutaneous tuberculosis and atypical mycobacterial infections in the context of an immunocompromised patient where AFB can be demonstrated on biopsy and cultures may be negative. In this clinical situation, PCR allows the prompt diagnosis and early institution of appropriate therapy. We have not found PCR to be a useful complement to the clinical and histologic diagnosis of "paucibacillary" forms of cutaneous tuberculosis.

Adult↗
PubMed1999

NAT2 slow acetylator genotype is associated with increased risk of lung cancer among non-smoking Chinese women in Singapore.

Among non-smokers, the factors resulting in lung carcinogenesis are poorly understood. We conducted a hospital-based case-control analysis of 294 Chinese women, of whom 217 were non-smokers, to evaluate the role of polymorphic N-acetyltransferase (NAT2) as a susceptibility factor for the disease. The proportion of slow acetylator genotypes among non-smoking cases (n = 92) and controls (n = 125) was 38.0 and 24.0%, respectively [odds ratio (OR) 2.0, 95% confidence interval (CI) 1.1-3.7]. No effect of NAT2 genotype was seen among smokers. Among non-smokers, the effect was marked for adenocarcinomas (OR 2.1, 95% CI 1.1-4.0). As NAT2 activity is known to modify risk of arylamine-induced carcinogenesis, our results suggest that exposure to arylamines in the environment may play a role in risk of lung cancer among non-smokers.

Acetylation↗
PubMed1999

Temporal trends and ethnic variations in asthma mortality in Singapore, 1976-1995.

BACKGROUND: A study was undertaken to examine temporal trends and ethnic differences in the asthma mortality rate in Singapore. METHODS: Asthma mortality rates in Singapore were estimated from vital data for the years from 1976 to 1995. Trends in sex and age specific (5-14, 15-34, 35-59, 60+ years) rates were obtained for four periods (1976-80, 1981-85, 1986-90, 1991-95) and for Chinese, Malay, and Indian subjects for the years when these data were available (1989-95). RESULTS: An increase in asthma mortality was observed in children aged 5-14 years from 0.21 per 100,000 person years in 1976-80 to 0.72 per 100,000 person years in 1991-95. No increases were noted in the other age groups but a small decrease was observed in the 1991-95 period for the 35-59 year age group. Marked ethnic differences in mortality rates were observed. In the group aged 5-34 years the asthma mortality rates were 0.5 per 100,000 in Chinese subjects, 1.3 per 100,000 in Indians, and 2.5 per 100,000 in Malay subjects. Similar 2-4 fold differences were observed in all other age groups. CONCLUSIONS: Apart from genetic factors, environmental exposures and medical care factors which influence asthma prevalence and severity are most likely to be the causes of the observed temporal trends and ethnic differences in the asthma mortality rate in Singapore, but further studies are needed to elucidate these more fully.

Adolescent↗
PubMed1999

The ECG "lead I sign" in cardiac disease--an indicator of coexisting obstructive pulmonary disease.

Two patients with co-existing cardiac disease and chronic obstructive pulmonary disease are described. The first patient had Wolff-Parkinson-White syndrome and the second patient had extensive anterior Q wave myocardial infarction. In addition to the distinctive ECG patterns of their cardiac abnormalities, both patients also showed the "lead I sign" which is a highly specific marker of chronic obstructive pulmonary disease. These two patients suggest that even in the presence of cardiac disease, the diagnosis of chronic obstructive pulmonary disease should be strongly suspected when the "lead I sign" is present.

Electrocardiography↗
PubMed1999

Hospital acquired pneumonia in the medical intensive care unit--a prospective study.

AIM OF STUDY: The aim of the study was to define the prevalence, risk factors, spectrum of organisms and sensitivity patterns, and the outcome in patients with severe hospital acquired pneumonia (HAP) in the Medical Intensive Care Unit (SCU) in a hospital in Singapore. METHOD: Consecutive patients admitted to the MICU over a 6-month period were studied and assessed daily to determine whether patients had developed HAP based on defined clinical criteria. Sputum or endotracheal aspirate was obtained and results recorded from each patient on admission and every subsequent three days throughout the stay in the MICU. Mortality during hospital stay was the main outcome measure recorded. RESULTS: A total of 136 patients (150 admissions) were studied; 24 patients were identified as having HAP. The prevalence of HAP was 17% [both ventilator-associated pneumonia (VAP) and pneumonia acquired from the ward (WAP)]. Cerebral disease was the main risk factor for VAP (OR 4.94, 95% CI 1.33-18.4). The spectrum of organisms which caused HAP were polymicrobial, Klebsiella pneumoniae, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus and coagulase negative Staphylococcus. The mortality of patients with VAP and WAP were 72.7% and 76.9% respectively. CONCLUSION: This study concludes that HAP in the MICU is common with a high mortality. The spectrum of organisms was comparable to previous studies.

Adult↗
PubMed1999

Long-term outcome and disease control in near-fatal asthma.

Patients who have survived an episode of intubation and mechanical ventilation for acute respiratory failure due to a severe and unresponsive asthmatic attack are considered to have experienced a near-fatal asthma (NFA) attack. Such patients are at a higher risk of similar severe attacks and hence of death in the future. The aims of the study were to: (i) evaluate the outcome; (ii) identify any persistent deficiencies in asthma management, and (iii) assess self-management knowledge in survivors of NFA. Ninety-three consecutive patients who had been treated for NFA in the Intensive Care Unit of an urban teaching hospital in Singapore from 1992 to 1997 were studied. All hospital records were reviewed retrospectively. Survivors were then invited to attend a questionnaire interview and to have lung function tests performed. Of the original cohort (OC) of 93 patients with NFA (mean age 55.2 years), 18 (19% OC) patients (mean age 64 years) had died while in hospital and 75 (81% OC) patients survived the initial episode of NFA and were discharged home (DH). The long-term outcome of this DH group was: 13 patients had died (17% DH) and 62 (83% DH) survived. Of these survivors, 35 were interviewed while 27 declined or were not contactable. This interview yielded the following information: (i) Hospitalisation in the past year: 66% had no hospital admission; of the 31.4% who had 2 or more admissions, most had a further NFA attack. (ii) Health care: The majority of patients (71.4%) were monitored by a single doctor. (iii) Patient knowledge of disease management was deemed good to fair for trigger avoidance (77%), for appropriate drug usage (97%). (iv) Satisfactory inhaler skill (80%). NFA is associated with a high intrahospital and long-term mortality. Although most survivors of NFA appeared to have satisfactory care and a fair understanding of medication usage, a significant minority continue to pose much morbidity and risk for death.

Aged↗
PubMed1999

Hospitalised low-risk community-acquired pneumonia: outcome and potential for cost-savings.

Fine et al. from USA have identified a sub-group of patients with community-acquired pneumonia (CAP) with a low risk of mortality and suggested that it may be cost-effective to manage them as outpatients. The aims of this study were: to evaluate the outcome of low risk CAP patients that were hospitalised in our local setting, and to gauge the number of such patients in order to estimate the potential cost-savings by treating them as outpatients, as well as the safety of such an approach. All patients with CAP admitted to our hospital from 1 April 1997 to 1 March 1998 were enrolled into this prospective cohort study. Low-risk patients were identified, and their hospital outcome compared with other patients. Hospitalisation charges were obtained from the Finance Department. There were 226 patients with CAP. The average age was 64 years with a range of 12 to 96 years. The median hospital stay was 6 days. Mortality was 13.7%. 16.8% required admission to the ICU; none of these were low-risk patients. There were 47 (21%) low-risk patients, and there was no mortality in this group. They had significantly shorter hospital stay (6.4 days versus 10 days) and lower hospitalisation charges ($2,160 versus $5,770) compared to other CAP patients. Only one low-risk patient had a positive blood culture. In conclusion, nearly one-fifth of our CAP admissions consisted of low-risk patients that experienced no mortality, and required a significantly shorter hospitalisation. The management of such patients who are young (< or = 50 years), with no serious co-morbidities in an outpatient setting may be a cost-effective strategy, and this group of patients consumed 9% of the total hospitalisation charges for CAP.

Aged↗
PubMed1998

The effect of inhaled budesonide on the diurnal variation in airway mechanics, airway responsiveness and serum neutrophil chemotactic activity in Asian patients with predominant nocturnal asthma.

The effectiveness of inhaled corticosteroids in the control of daytime symptoms in asthma is well established, but the specific use against nocturnal asthma has not been systematically studied in Asian patients. This study examined the effect of treatment with inhaled budesonide on the nocturnal variation in measurements of airway calibre, bronchial hyperresponsiveness to inhaled histamine and circulating neutrophil chemotactic activity in Asian patients with nocturnal asthma. Thirty patients, with nocturnal asthma, were randomized into a 2-month, double-blind, parallel group study. Twice as many subjects were allocated to the group who received two consecutive months of inhaled budesonide 1600 microg daily as to the group who received placebo followed by budesonide. Spirometry, lung mechanics, bronchial hyperresponsiveness and serum neutrophil chemotactic factor (NCA) were measured at 16.00 h, 22.00 h and at 04.00 h on 3 days and nights, 4 weeks apart before and after either placebo or budesonide. The combined measurements for the two groups at 04.00 h before and after treatment with budesonide were: forced expiratory volume in 1 s (FEV1) mean (SEM) litres 1.34 (0.17) before, 2.00 (0.19) after; thoracic gas volume (TGV) litres 3.05 (0.32) before, 2.25 (0.14) after; specific airway conductance (sGaw) (cmH20.0 sec)(-1) 0.39 (0.07) before, 1.16 (0.17) after; PD20 microg geometric mean 1.16 before, 44.74 after; neutrophil chemotactic activity (NCA) in units of graduations of migration 98.8 (4.2) before, 101 (14.2) after. The data showed that short and intermediate term high dose inhaled budesonide is an effective specific treatment for nocturnal asthma in Asian patients, resulting in marked improvements in symptoms and in lung mechanics, and reductions in the diurnal variations in bronchial hyperresponsiveness, before any change could be demonstrated in a circulating marker of airway inflammation.

Administration, Inhalation↗
PubMed1998

Prevalence of snoring and sleep breathing-related disorders in Chinese, Malay and Indian adults in Singapore.

This study investigated the prevalence of snoring and symptoms of sleep breathing-related disorders in the multi-ethnic population of Singapore (3 million people, comprising 75% Chinese, 15% Malay and 7% Indian). A multistaged, area cluster, disproportionate stratified, random sampling of adults aged 20-74 yrs was used to obtain a sample of 2,298 subjects (65% response), with approximately equal numbers of Chinese, Malay and Indian and in each 10 yr age group. An interviewer-administered field questionnaire was used to record symptoms of snoring and breathing disturbances during sleep witnessed by a room-mate and other personal and health-related data. The weighted point estimate (and 95% confidence interval) of the whole population prevalence of snoring was 6.8% (53-83). There were pronounced ethnic differences among Chinese, 6.2% (4.4-8.1); Malay, 8.1% (6.1-10.2) and Indian, 10.9% (85-13.4). The minimum whole population prevalence by the most restricted symptom criteria for defining sleep breathing-related disorder was 0.43% (0.05-0.8%). Similar marked ethnic differences in rates were observed using various symptom criteria. The ethnic differences in sleep breathing symptoms paralleled the differences in body mass index, neck circumference and hypertension, but statistically significant differences remained after adjustment for sex, age and these known associated factors. Marked ethnic differences in snoring and sleep breathing-related disorders were observed in Chinese, Malays and Indians in Singapore, which were only partly explained by known factors of sex, age and body habitus.

Adult↗
PubMed1997

Comparative usefulness of PCR in the detection of Mycobacterium tuberculosis in different clinical specimens.

The role of the polymerase chain reaction (PCR) in the diagnosis of tuberculosis in clinical practice remains to be defined; most results have been based on sputum samples. This study systematically compared the relative sensitivity and specificity of a single simplified method for different clinical samples. A wide range of clinical samples, including sputum, bronchoalveolar lavage fluid, cerebrospinal fluid, pleural fluid, gastric aspirate, pus and tissues (both fresh and paraffin-embedded) was tested. This method did not require routine DNA extraction before PCR, and consisted of an optimised single tube PCR amplification designed with different sets of time and temperature profiles. A total of 398 samples from 293 patients was studied. The sensitivity was 100% for all types of specimens, while the specificity ranged from 95% for sputum to 88% for bronchoalveolar lavage fluid and pleural fluid and to 85% for non-pulmonary specimens. This study showed that it was possible to employ a single simplified method with minor modifications for a wide range of specimens in clinical practice without loss of sensitivity and specificity.

Blotting, Southern↗
PubMed1997

Population based standards for pulmonary function in non-smoking adults in Singapore.

Ethnic differences in lung function are well recognized, hence the use of normative data should therefore be based on reference equations that are derived specifically for different ethnic groups. We have collected data (n = 406) for population-based reference values of lung function from randomly selected samples of healthy non-smoking adults of both gender (aged 20-79 years) for each of the three major ethnic groups (Chinese, Malay and Indians) in Singapore. Lung function forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, diffusion capacity (transfer factor) for carbon monoxide (DLCO), total lung capacity (TLC), residual volume (RV), RV/TLC and functional residual capacity (FRC) was measured using standardization procedures and acceptability criteria recommended by the American Thoracic Society. Lung function values were predicted from age, height, weight, body mass index (BMI) and transformed variables of these anthropometric measures, using multiple regression techniques. Ethnic differences were demonstrated, with Chinese having the largest lung volumes and flow rates, and Indians the smallest. These prediction equations provide improved and additional (TLC, RV, RV/TLC, FRC) population-based reference values for assessment of pulmonary health and disease in Singapore.

Adult↗