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Biomedical subjects

W C Tan

Publications and source records attributed to W C Tan.

At least 19 recordsLinked to original sources

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

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

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

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

Enhancement of photodynamic therapy in gastric cancer cells by removal of iron.

BACKGROUND: Aminolaevulinic acid (ALA) is an endogenous substrate in the haem biosynthetic pathway. Protoporphyrin IX (PPIX), the immediate haem precursor in the pathway, has photoexcitable properties. Exogenous ALA has been used previously as a precursor agent in photodynamic therapy (PDT). Its main advantage is a short half-life and hence reduced incidence of skin photosensitivity. ALA can be toxic, however, causing, for example, transient increases in liver enzyme concentrations when given systemically and this may be dose related. AIM: To assess whether accumulation of PPLX and ultimately the efficacy of PDT could be improved by modulating both ends of the haem biosynthetic pathway. METHODS: Gastric cancer cells (MKN 28) were incubated with ALA (0-1000 mumolar) and desferrioxamine (0-800 mumolar) for 24 hours before exposure to argon-pumped dye laser (630 nm) at different energy levels (0-40 J/cm2). Cell viability was assessed by use of the methyl-tetrazolium (MTT) assay four hours after exposure to light. RESULTS: Total PPIX accumulation increased linearly with increasing extracellular concentrations of ALA up to 1 mmolar (r = 0.973, p < 0.005). Adding 200 molar of desferrioxamine trebled PPIX accumulation over the same period of incubation. Cell viability after exposure to light decreased with low doses (0-30 mumolar) of desferrioxamine (r = 0.976, p = 0.024). However, higher doses of desferrioxamine (more than 40 molar) seemed to confer a protective effect against PDT. CONCLUSION: PDT using ALA can be improved by removal of available iron with desferrioxamine. The reason for the protective effect of desferrioxamine seen at higher doses is not clear.

Aminolevulinic Acid

Advance directive: a study on the knowledge and attitudes among general practitioners in Singapore.

Recent calls for the Advance Directive (AD) to be implemented in Singapore have raised issues regarding the dearth of knowledge and attitude among local healthcare professionals. The present study aims to find out the attitudes and to assess the extent of knowledge regarding the AD among General Practitioners (GPs) in Singapore. This was a cross-sectional, descriptive survey with a sample size of 199 doctors randomly drawn from the Singapore Medical Council list, forming a sampling fraction of 16%. The response rate obtained was 78%. The results showed that while GPs generally supported the concept of the AD, their views were divided on the issue of legislation. They had a basic knowledge of the AD, such as the definition of the AD, that it could be revoked, and the continuity of care and pain relief even after withdrawal of life-sustaining measures. However, only half knew when it should be executed. Many GPs were concerned that the legislation of the AD would lead to the acceptance of euthanasia. They believed that they were in the best position to decide on the treatment of choice for their patients, although they would respect their patients' wishes.

Adult

Helicobacter pylori eradication--comparison of three drug regimens and symptomatic assessment in duodenitis and antral gastritis.

Helicobacter pylori (Hp) eradication in peptic ulcer disease is associated with a greatly reduced recurrence rate. The optimal drug regimen for HP eradication remains uncertain. It is also unclear if eradication of Hp in duodenitis and antral gastritis improves symptoms. The aims of this study were to compare the efficacy of three drug regimens in the eradication of Hp and to assess if Hp eradication improved symptoms in patients with duodenitis and antral gastritis. Patients (n = 79) found to have duodenal ulcer, duodenitis and/or antral gastritis with a positive urease test (CLO) at endoscopy were allocated to one of the three regimens: A. omeprazole 20 mg b.d. and clarithromycin 500 mg t.d.s. for two weeks (n = 27), B. De-Nol 240 mg b.d. for four weeks, metronidazole 400 mg t.d.s. and amoxicillin 500 mg t.d.s. for one week (n = 26), and C. omeprazole 20 mg b.d. and amoxicillin 500 mg t.d.s. for two weeks (n = 26). In conclusion, traditional 'triple' therapy with bismuth and two antibiotics achieved the highest Hp eradication rate and was best tolerated. Recolonisation with Hp was uncommon after eradication. Dyspeptic symptoms improved with Hp eradication in duodenitis and antral gastritis.

Adult

Severe asthma.

OBJECTIVE: To determine the morbidity and mortality of severe asthmatic patients needing intensive care in Singapore. DESIGN: Retrospective review of admissions from January 1987 to March 1993. SETTING: Urban teaching hospital. PATIENTS: Forty-eight patients with forty-nine admissions with severe asthma requiring admission into the medical intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-eight patients with forty-nine admissions with severe asthma requiring admission into the medical intensive care unit were identified during the study period. The majority (69%) were admitted directly into the intensive care from the emergency room, and 16 cases (33%) had cardiorespiratory arrest, of whom half survived hypoxic brain damage. Mechanical ventilation was needed in 30 cases (61%), with a mean duration of 3.3 days, and 2 pneumothoraces were recorded. Those who needed mechanical ventilation had significantly higher arterial pCO2 (98 mmHg vs 62 mmHg) and a lower arterial pH (7.1 vs 7.3). However, not all patients with hypercapnia (> 50 mmHg) needed mechanical ventilation. Hospital mortality was 12% (6 cases), while two others with hypoxic brain damage died shortly after hospital discharge. Mortality was not predicted by previous need for mechanical ventilation, length of asthma, or age. For the ventilated group alone, hospital mortality was higher at 20%. On an average follow-up of 133 weeks, there was only one death. Mean potassium level was 3.9 mmol/L with 13 cases (28%) of hypokalemia (< 3.6 mmol/L). CONCLUSION: Severe asthma was associated with an appreciable mortality. Hypercapnia did not guarantee the need for mechanical ventilation. For those that survived their acute episode, there was one mortality out of 40 survivors after an average of 2 years of follow-up.

Adult

Necrotizing fasciitis--an unusual presentation of miliary mycobacterium tuberculosis.

We report an immunocompromised patient who presented with necrotizing fasciitis as the initial presentation of miliary tuberculosis. The diagnosis of miliary tuberculosis was delayed resulting in prolonged morbidity and hospital stay. The lesson from this report is that tuberculosis should be recognised as an uncommon cause of necrotizing fasciitis in an immunocompromised patient, especially if the response to prompt and standard initial treatment is unsatisfactory.

Anti-Bacterial Agents

Eradication of high-grade dysplasia in columnar-lined (Barrett's) oesophagus by photodynamic therapy with endogenously generated protoporphyrin IX.

BACKGROUND: High-grade dysplasia in columnar-lined (Barrett's) oesophagus presents a difficult therapeutic dilemma. Choices for management are endoscopic surveillance to detect a cancer or oesophagectomy. One carries the risk of missing invasive cancer, the other carries worrying morbidity and mortality. We have used endoscopic photodynamic therapy to eradicate high-grade dysplasia. METHODS: After the oral administration of 5-aminolaevulinic acid, the accumulation of the endogenously generated photosensitiser protoporphyrin IX was measured with quantitative fluorescence microscopy. Five patients with histologically confirmed high-grade dysplasia were treated with endoscopic photodynamic therapy with 630 nm laser light to activate the photosensitiser. FINDINGS: Protoporphyrin IX accumulated in the dysplastic epithelium rather than the adjacent stroma. Selective necrosis of the dysplastic epithelium in columnar-lined oesophagus occurred after light activation. High-grade dysplasia was eradicated in all patients and squamous regeneration occurred after acid suppression with a protonpump inhibitor. There were no complications or recurrence of dysplasia after 26-44 months' endoscopic and histological follow-up. In two cases we saw non-dysplastic Barrett's epithelium underneath regenerative squamous mucosa. INTERPRETATION: High-grade dysplasia in columnar-lined oesophagus can be eradicated by endoscopic photodynamic therapy with endogenously generated PpIX. Remaining non-dysplastic Barrett's epithelium will require surveillance, but overall the technique has interrupted or delayed the worsening of the dysplasia through to carcinoma. This technique may prevent the need for surgical excision in these patients.

Aged

Simplified method for measuring urinary leukotriene E4.

The conventional method for measuring urinary leukotriene E4 (LTE4) is by reversed-phase high-performance liquid chromatography (RP-HPLC), followed by radioimmunoassay (RIA) or enzyme immunoassay (EIA). We measured urinary LTE4 levels by two methods, HPLC with EIA and EIA alone after initial crude extraction of urine using an octadecyl reversed-phase extraction cartridge (Sep-Pak). Ninety-three urine samples from normal subjects and patients with bronchial asthma and adult respiratory distress syndrome were tested. The results showed that urinary LTE4 levels measured by EIA significantly correlated with those measured by HPLC plus EIA in the three groups (r = 0.88, 0.85, 0.68). The absolute values of urinary LTE4 measured by EIA without HPLC purification were higher than by EIA with HPLC purification. This suggests that HPLC may not be necessary for routine urinary LTE4 quantitation in different clinical situations.

Adult

DNA diagnosis of pulmonary infections: particular emphasis on Mycobacterium tuberculosis.

The past two decades have brought significant changes to the clinical laboratory. Microbiologists now have highly sensitive, rapid and specific molecular methods of identifying infectious agents by the direct detection of DNA or RNA sequences unique to a particular organism. Advanced DNA technology such as nucleic-acid hybridization, PCR and DNA fingerprinting have been used in the direct detection of causative organisms in clinical specimens, with resultant benefits such as increased sensitivity and specificity of the diagnostic approach and reduction of turnaround time. This review outlines a brief description of the various DNA diagnostic tools used in the detection of pulmonary infections with emphasis on their applications in the diagnosis of Mycobacterium tuberculosis.

DNA Fingerprinting

Genome macrorestriction analysis of sequential Pseudomonas aeruginosa isolates from bronchiectasis patients without cystic fibrosis.

The respiratory tracts of bronchiectasis patients may be persistently colonized with Pseudomonas aeruginosa, despite intensive chemotherapy. The organism may undergo phenotypic changes in these patients, providing misleading typing results by conventional methods. We prospectively studied eight bronchiectasis patients without cystic fibrosis over a period of 1 year. A high microbial load of P. aeruginosa was found in 70% of sputum samples collected. Of these, 55 sequential P. aeruginosa isolates were characterized by a genotyping method, pulsed-field gel electrophoresis, to overcome the problem of differentiating the P. aeruginosa strains during chemotherapy. Genome macrorestriction fingerprinting patterns were analyzed after digestion with XbaI restriction endonuclease. Of the eight patients, six harbored a single dominant strain of P. aeruginosa, with an intrapatient macrorestriction similarity pattern range of 96 to 100%. The other two patients were infected with mixed bacterial isolates including P. aeruginosa. However, diversity was observed in the P. aeruginosa isolates from all eight patients, with a relatedness of only 55 to 65%. The study further strengthens the fact that pulsed-field gel electrophoresis can be used efficiently and effectively to differentiate P. aeruginosa strains in bronchiectasis patients without cystic fibrosis.

Adult

Severe community-acquired pneumonia in Singapore.

BACKGROUND: There has been no previous study documenting the aetiology and prognosis of severe community-acquired pneumonia in Singapore. Patients with severe community-acquired pneumonia (SCAP) needing admission to a medical intensive care unit in Singapore were studied retrospectively. METHODS: All patients admitted to the medical intensive care unit at National University Hospital from June 1991 to February 1993 with a diagnosis of community-acquired pneumonia were entered into the study. All patients had blood cultures, sputum cultures, serologies for Legionella and mycoplasma drawn on admission. APACHE II scores were determined prospectively. RESULTS: Fifty-nine consecutive cases from June 1991 to February 1993 were identified with a mean age of 61 (SD 17) years. Nearly all the cases needed mechanical ventilation (90%) and overall mortality was 63%. An aetiological agent was identified in the majority of cases (68%), with Klebsiella pneumoniae being the most common agent (9 cases, 15%). Haemophilus influenzae and Streptococcus pneumoniae were identified in 8% (5 cases) and 5% (3 cases) of cases respectively. Pseudomonas pseudomallei was identified in 4 cases (7%) with a 100% mortality. Overall, gram-negative organisms were identified in 47% of cases. APACHE II was significantly higher in non-survivors. Age, creatinine levels, and the presence of bacteraemia were not prognostic features. CONCLUSION: SCAP in Singapore carries a high mortality with the predominance of gram-negative organisms. Empiric antibiotics should include gram-positive and gram-negative coverage with specific coverage for Pseudomonas pseudomallei.

Adolescent

Effect of glucose on the respiratory burst of circulating neutrophils from asthmatics.

The respiratory burst is dependent on a source of glucose. We wished to investigate the effect of glucose on the superoxide production of circulating neutrophils. Superoxide production of neutrophils was significantly enhanced by glucose concentration of from 1 to 50 mmole/liter in the medium. The neutrophils from asthmatics in both the acute and remission phases showed greater production of superoxide than those of controls. When the neutrophils were made to undergo the respiratory burst, initially in the absence of glucose, and thereafter in the presence of 5 and 20 mmole/liter glucose, the rate of superoxide formation with higher glucose medium was decreased in the control cells but significantly increased in the cells of the acute asthmatics in remission. It is concluded that glucose as an energy source is potentially critical in determining the rate of the respiratory burst and that the neutrophils from asthmatic subjects in some way have an enhanced uptake or metabolism of this substrate. Glycemic status may then have some role in determining the amount of superoxide production, and therefore airway inflammation, in asthma.

Adolescent

Tuberculosis and invasive pulmonary aspergillosis in a young woman with a myelodysplastic syndrome.

A 29-year-old Chinese woman developed pyrexia, multiple skin abscesses and bilateral fine nodular lung infiltrates about 3 months after the commencement of therapy for idiopathic thrombocytopenic purpura (ITP). Pseudomonas aeroginosa was isolated from the abscesses but multiple blood and sputum cultures, as well as a broncho-alveolar lavage did not yield any microorganisms. The persistence of fever and pulmonary infiltrates warranted an open lung biopsy which provided a definitive diagnosis of tuberculous-aspergillus granulomatous lung disease. Bone marrow re-examination revised the primary haematological disorder to that of a trisomy 8 associated myelodysplastic syndrome.

Adult