A 39-year-old smoker with effort dyspnea, normal spirometry results, and low diffusing capacity.
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Biomedical subjects
Publications and source records attributed to T K Lim.
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An electrochemical reactor employing activated carbon fibers (ACF) was constructed for the disinfection of bacteria in drinking water. The application of an alternating potential of 1.0 V and -0.8 V versus a saturated calomel electrode, for disinfecting and desorbing bacteria, enabled reactor operation for 840 h. Drinking water was passed through the reactor in stop/flow mode: 300 ml/min flow for 12 h and no flow for 12 h, alternately. The bacterial cell density in treated water was always been less than 20 cells/ml. It was also found that the formation of biofilm on the ACF reactor caused an increase in current, enabling the self-detection of microbial fouling.
The aim of this study was to examine the inter-relationships between the different effects of deep breaths and histamine provocation on airway function in patients with bronchial asthma. Group 1 consisted of 38 consecutive out-patients with newly diagnosed mild asthma, group 2 consisted of 20 patients with bronchial asthma of varying severity who were studied during clinical remission. We measured bronchial responsiveness (BR) to histamine inhalation as the dose of histamine which provoked a 20% fall in FEV1 (PD20). The fall in forced vital capacity (FVC) after inhaling the highest dose of histamine during each BR test was calculated and expressed as percentage of the value measured at baseline (delta FVC in percentage). We studied the effects of deep breaths on airway caliber in group 2 patients by comparing isovolumic flow rates on partial (P) and maximal (M) forced expiratory flow volumes curves expressed as the M/P ratio. The changes in residual volume (RV) after deep breaths (delta RV) were expressed as a percentage of the largest VC measured on the composite M and P curves. The patients in group 1 had significantly higher PD20 and lower delta FVC than patients in group 2. There was, however, no significant correlation between PD20 and delta FVC measurements in individual patients (r < 0.1, P > 0.05). The M/P ratio was significantly related to delta FVC (r = -0.6, P < 0.006). There was also a significant positive relation between the magnitude of increase in residual volume following deep breaths (delta RV) and the degree of fall in FVC following histamine inhalation (delta FVC) (r = 0.65, P = 0.001). This significant relationship between the degree of airway closure after a deep breath and airway closure after histamine challenge is a new finding. In patients with bronchial asthma, the effects of a deep breath on airway function may be indicative of the tendency for airway closure during BR testing.
OBJECTIVE: To compare the efficacy of adjunctive intrapleural streptokinase (SK) with simple closed chest tube drainage (Drain) in the treatment of empyemas and complicated parapneumonic effusions. METHOD: This was a controlled study of 52 patients (mean age, 57 years; 41 men) with pleura space sepsis. Forty patients (77%) had empyema and 12 had complicated parapneumonic effusions. Twenty-nine patients were treated with Drain only while 23 received, in addition, repeated daily SK, 250,000 U in saline solution (mean, 5.3 days). RESULTS: The two groups of patients had comparable degrees of peripheral blood leukocytosis, frequency of loculated effusions, pleural fluid pH, and lactate dehydrogenase levels. Infective organisms were isolated in 54% of which 32% were anaerobic and 21% were polymicrobial infections. The incidence of surgical decortication was 17% and mortality was 15%. A significantly larger volume of pleural fluid was drained from patients in the SK treatment group (2.0 [1.5] L) than those in the Drain treatment group (1.0 [1.01] L). There were no significant differences, however, between the two treatment groups in terms of duration before defervescence, duration of hospital stay, the need for surgical intervention, or mortality rates. CONCLUSION: We conclude that thrombolytic therapy increased the volume of fluid drained from pleural empyemas but did not markedly reduce morbidity and mortality.
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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.
The death rate from pneumonia in Singapore has increased steadily over the past decade. The emerging respiratory pathogens may have contributed to this increased mortality. New challenges have arisen from changes in the characteristics of the host and the susceptibilities of the various pathogens to antibiotics. There has been a 60-fold increase in the incidence of penicillin resistance in Streptococcus pneumoniae, the major pathogen for community-acquired pneumonia (CAP). Gram-negative bacilli are the major pathogens in severe CAP with Klebsiella pneumonia being the most frequently isolated organism. There has been a small increase in the number of cases of Legionnaire's disease and a marked increase in the incidence of melioidosis. While the overall incidence of tuberculosis has been unchanged, the number of non-residents with tuberculosis has doubled in the past 5 years. The rising prevalence of human immunodeficiency Virus infection is reflected in an increasing number of apparently healthy young men who present with CAP caused by Pneumocystis carinii. There is increasing resistance to antibiotics among gram-negative bacilli and Staphylococcus aureus, the dominant pathogens in hospital-acquired pneumonia. New strategies are urgently needed to prevent the emergence of pathogens in the hospital environment which may be resistant to all known antibiotics.
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.
Pulmonary dendritic cells (DC) are present in extremely small numbers, but they are the most potent antigen-presenting cells in the lungs. Pure populations of DC can be isolated from the lung following collagen digestion, Percoll gradient centrifugation, removal of phagocytic cells and flow cytometric sorting for cells which exhibit high levels of surface major histocompatibility complex (MHC) class II molecules. Exogenous GM-CSF enhances this immunostimulatory capacity of the pulmonary DC. Soluble factors produced by type II airway epithelial cells and interstitial macrophages also enhance the immunostimulating capacity of pulmonary DC while alveolar macrophages suppress it. Thus, the function of DC may be regulated by locally produced cytokines. Corticosteroids are widely used as immunosuppressive agents in pharmacotherapy. While these agents are known to inhibit T cell proliferation and macrophage activation, their effects on DC are not known. We found that dexamethasone (Dex) pretreatment resulted in about a 50% reduction in the immunostimulatory capacity of rat pulmonary DC. This was associated with downregulation of MHC class II (Ia) expression. Dex-induced suppression of DC function could be restored with GM-CSF. We conclude that corticosteroids downregulate antigen-presenting capacity by direct suppression of pulmonary DC. This immunosuppressive effect of corticosteroids on DC may, however, be abrogated by exogenous GM-CSF. Corticosteroids and GM-CSF are therapeutic agents with potent direct immunomodulating effects on DC.
The efficacy of mask-applied continuous positive airway pressure (CPAP) in the treatment of patients with acute severe exacerbations of chronic obstructive pulmonary disease (COPD) was examined. Ten patients with severe exacerbation of COPD who had deteriorated during conventional therapy were treated with face-mask delivered CPAP (+5 cmH2O; Downs Vital signs Inc., New Jersey, USA) instead of tracheal intubation and mechanical ventilation. The patients that were selected required mental alertness, intact upper airway reflexes, the clinical signs of dynamic hyperinflation and a positive end-expiratory pressure auto-(PEEP) manifested as expiratory wheeze and grunting. Nine out of 10 patients responded promptly to mask-CPAP with less distress, better oxygenation, lower respiratory and pulse rates. There was no significant change in arterial carbon dioxide tension with mask-CPAP treatment. One patient deteriorated on mask-CPAP and required intubation and mechanical ventilation. Three patients died (none of these patients died during the acute period of exacerbation). It was concluded that Mask-CPAP may be an alternative to mechanical ventilation in the treatment of selected patients with severe hypercapnic exacerbations of COPD.
We conducted a three-month prospective study on the profile of 70 acute adult asthmatic patients presenting to the Accident and Emergency Unit of a general hospital. The overall background asthmatic activity, clinical features of current exacerbation, maintenance drug treatment, gross psycho-social problems, previous experience of near-fatal asthma, and admission and relapse rates were documented. Ninety percent of the presentations were within 24 hours of the initial attack, with an average pre-hospital therapy duration of 6.5 hours. Sixty-seven percent sought further treatment after failure to find relief from their salbutamol metered-dose inhalers. Sixteen percent did not receive any treatment before presentation. Ten percent gave a past history of mechanical ventilation for severe or near fatal asthma. The majority (94%) had asthmatic symptoms in the mild to moderate range. About half (46%) had attended the Emergency Room (ER) at least once in the previous six months. On average, patients were on two items of drugs and 23% were on maintenance inhaled steroids. One-third (33%) of the patients were found to have psycho-social problems relating to their condition. The admission rate was 37% with relapse rate following ER discharge of 13%. The study showed a high proportion of patients with psycho-social problems relating to asthma, and a subset of patients with frequent visits to the ER. It also revealed the infrequent use of prophylactic therapy.
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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.
We studied prospectively the microbiologic findings, management, including the use of intrapleural streptokinase to improve pleural drainage, and outcome of 33 patients with complicated parapneumonic effusions (6) frank empyema (27) treated by our unit over a 4-year period. The mean age was 61 years, with more male (26) than female (7) patients. Seventy-nine percent of the patients had some form of underlying illness, especially chronic lung disease (46%), followed by diabetes mellitus (23%). Fifteen percent of the pleural collections were loculated. Pleural fluid cultures were positive in 58%, Staph aureus and Kleb pneumoniae being the most prevalent aerobic isolates. The incidence of anaerobic isolates was 32%. Besides empirical antibiotics, all patients had drainage of the pleural collections at diagnosis. Four patients were treated with needle aspiration; 28 (85%) required thoracostomy tube drainage for a mean of 8 days, 5 of these went on to surgical decortication. Thirteen patients received intrapleural streptokinase (SK) to facilitate drainage, with significant increase in the volume drained. The mean duration of stay for the whole group was 22 days. The administration of intrapleural SK did not significantly shorten the duration of hospital stay. There were six deaths (18%), none as a direct result of the empyema. We describe a therapeutic approach to parapneumonic effusions and empyema which tailors the interventional modality to the clinical stage of disease.
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Two gene sequences specific for Mycobacterium tuberculosis were evaluated for the diagnosis of pulmonary tuberculous (PTB) in pleural fluid (PF), bronchoalveolar lavage fluid (BAL) and sputum (Sp). The 240 bp sequence (nts 460-700) coding for the MPB 64 protein coding gene and the 123 bp IS6110 insertion element present in multiple copies in the mycobacterial genome were amplified using the polymerase chain reaction. Fifty-nine clinical specimens were studied. The diagnosis of PTB was confirmed by positive M. tuberculosis cultures in 14 specimens, and by the presence of characteristic histological features of granuloma and Langerhan's giant cells on pleural biopsy in 3 PF specimens through cultures for M. tuberculosis were negative. The remaining 42 specimens were obtained from patient's with non-tuberculosis pulmonary infections or malignancy, and these served as negative controls. Our results showed that the IS6110 insertion element and MPB 64 gene sequence were detected in all 14 culture positive PTB cases, although detection of the latter sequence required both DNA amplification and oligonucleotide hybridization. There was however one false positive specimen with the MPB 64 detection protocol. More importantly, both the MPB 64 sequence and IS6110 insertion element protocols were unable to detect M. tuberculosis DNA in the 3 PF samples diagnosed by histological characteristics on pleural biopsy and culture negative. We conclude that DNA amplification for M. tuberculosis-specific sequences is a useful method for rapid diagnosis of PTB in culture positive specimens. However, the false negative results with TB culture negative cases of tuberculosis pleurisy, limits its usefulness for the diagnosis of tuberculous pleurisy.
One hundred and one cases of Klebsiella bacteraemia from the National University Hospital, Singapore, were reviewed retrospectively. There were 54 (53.5%) males and 47 (46.5%) females. Mean (+/- SE) age was 54 (+/- 2.4) years. Overall mortality was 26%. Nosocomial infections accounted for 20%. Underlying diabetes mellitus and malignancy were present in 36 and 26% respectively. The source of the bacteraemia was not known in 33% of cases, 17% had liver abscess, 29% had urinary tract infections, 9% had pneumonia, 10% had an abscess separate from the liver, and 3% had biliary sepsis. Elevated alkaline phosphatase (> 100 U-1) was seen in all cases of liver abscess (sensitivity 100%, specificity 27%). Nonsurvivors had a significantly lower platelet count than survivors (104 +/- 25 x 10(9)/l vs. 176 +/- 15 x 10(9)/l, unpaired t-test P < 0.05), and a platelet count of less than 150 x 10(9)/l was associated with a significantly higher mortality (37% vs. 11%, chi 2 P < 0.01). Nosocomial infection was associated with 45% mortality, whereas community-acquired infection had a lower rate of 21%, this was not statistically significant. Seventy-eight per cent of these Klebsiella isolates were sensitive to gentamicin and cotrimoxazole, and 100% to imipenem.