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Biomedical subjects

T K Lim

Publications and source records attributed to T K Lim.

At least 37 records · Page 2Linked to original sources

Construction of electrochemical flow immunoassay system using capillary columns and ferrocene conjugated immunoglobulin G for detection of human chorionic gonadotrophin.

In this paper is reported a miniaturized flow immunoassay system. Ferrocenecarboxylic acid (Fc) conjugated with anti-HCG immunoglobulin G (IgG) antibody (Fc-IgG) was prepared, and used as a novel analytical reagent. The system consists of the immunoreaction section, the capillary column packed with cation exchange resin, and the flow cell for electrochemical detection of Fc-IgG. Antibody-antigen complexes were separated from their free conjugate on the basis of differences in isoelectric point (pI) using a cation exchange capillary column. The assay yielded a linear relationship between signal and HCG concentration in the range 0-2000 mIU/ml. This simple technique enables the assay of HCG within 2 min. The cation exchange capillary column was regenerated by occasional elution with malonate buffer (pH 6.0) containing 0.5 M NaCl, to remove free conjugate. Free conjugate recovered in this manner could be reused up to eight times without significant decreases in the sensitivity of the immunoassay. This electrochemical flow immunoassay requires only minute quantities of serum and generates highly reproducible results.

Antigen-Antibody Complex↗

Management of parapneumonic pleural effusion.

Parapneumonic pleural effusion is a common and potentially serious complication of pneumonia. The management of parapneumonic pleural effusion involves early diagnosis, adequate empiric antibiotic cover, and appropriate risk categorization. High-risk patients require safe and expedient drainage of the infected pleural space. The management options include thoracentesis, tube thoracostomy, adjunctive intrapleural fibrinolytic therapy, and surgical drainage. The methods of surgical drainage include thoracoscopy, thoracotomy, and decortication. The relative clinical efficacy of these treatment options has been studied in a small number of controlled clinical trials, the results of which have been systematically reviewed by expert panels. Based on the limited clinical evidence, expert reviewers were unable to recommend a best method of pleural drainage. However, the consensus is that an aggressive approach with early surgical drainage results in shorter hospital stays and may be more cost-effective than conservative management. This review discusses the clinical evidence and describes an aggressive sequential management strategy that combines intrapleural fibrinolysis with early surgical drainage.

Clinical Protocols↗

Empirical treatment of chronic cough--a cost-effectiveness analysis.

Chronic cough of unknown etiology is often difficult to diagnose, thus, there exists controversy regarding the management of such patients. Although the ACCP (American College of Chest Physicians) statement in 1998 recommended that treatment should follow testing, recent evidence suggests that empirical treatment of GERD is more cost-effective than testing followed by treatment, in both chronic cough and non-cardiac chest pain. In this paper, we evaluated the cost-effectiveness in managing patients with chronic unexplained cough by building a decision model, and compared the cost-effectiveness of six most common management strategies. The outcome of our analysis demonstrates that empirical treatment is the cheapest option, while testing followed by treatment is the most expensive option with the shortest time course.

Chronic Disease↗

Early discharge of patients hospitalized with acute asthma: a controlled study.

There is no consensus on the optimal length of stay and timing of release from hospital in patients admitted with acute asthma. We hypothesize that it might be safe to discharge patients from hospital once they have responded clinically to intensive anti-asthma treatment. In a non-randomized prospective controlled study, we compared two discharge protocols in consecutive patients admitted for acute severe exacerbations of bronchial asthma. Patients in group A were discharged after remission of signs and symptoms and those in group B after improvement but before complete remission of signs and symptoms. Peak expiratory flow rates (PEFR) were monitored but were not used as discharge criteria for either group. Patients with complicating disease and who were likely to be non-compliant were excluded. The length of hospital stay (LOS) and best PEFR at discharge were significantly lower in group B (87 admissions) than group A (80 admissions). The mean (+/-SD) LOS was 1.8(+/- 1) days vs. 3.5(+/- 1.4) days and best PEFR was 58(+/- 17)% predicted versus 71(+/- 15)% predicted respectively (P < 0.001 for both variables). No patient in either group relapsed within 4 weeks of discharge from hospital. We concluded that the release of asthmatics who respond promptly to intensive treatment and are compliant with medication despite incomplete resolution of symptoms, signs and PEFR at the time of discharge from hospital may not be associated with increased risk of early relapse.

Acute Disease↗

Relationship between estimated pretest probability and accuracy of automated Mycobacterium tuberculosis assay in smear-negative pulmonary tuberculosis.

BACKGROUND: The AMPLICOR assay (Roche; Branchburg, NJ), a rapid direct amplification test for Mycobacterium tuberculosis, has only been licensed for use in smear-positive respiratory specimens. However, many patients with pulmonary tuberculosis (PTB) have smear-negative disease. The clinical utility of this test in patients with smear-negative PTB is unknown. OBJECTIVE: To evaluate the effect of pretest probability of PTB estimated by chest physicians on the accuracy of the AMPLICOR assay in patients with smear-negative PTB. DESIGN AND METHODS: A prospective study of consecutive patients suspected of having smear-negative PTB. Two chest physicians estimated the pretest probability of active disease (high, intermediate, and low categories). Respiratory specimens were examined with radiometric broth medium cultures and with the AMPLICOR assay for M tuberculosis. The decision on a final diagnosis of PTB was blinded to the AMPLICOR results. RESULTS: Active PTB was diagnosed in 25 of 441 patients (5.7%). The AMPLICOR assay had an overall sensitivity of 44% and a specificity of 99%. Results of the assay were negative in seven patients with culture-negative PTB. The proportions of patients in the high, intermediate, and low pretest groups were 4.5%, 19.7%, and 75.7%, respectively. The incidence of PTB for each group was 95%, 3.4%, and 0.9%, respectively. The sensitivities of the AMPLICOR assay in the three groups of patients were 47%, 33%, and 33%, respectively, while the specificities were 100%, 98%, and 99%, respectively. CONCLUSIONS: In patients suspected of having smear-negative PTB, the following conclusions were drawn: (1) the incidence of active PTB was low; (2) pretest estimates accurately discriminated between patients with high and low risk of PTB; (3) the risk of PTB was overestimated in the intermediate group; and (4) the utility of the AMPLICOR assay in the intermediate-risk group may be limited by the overestimation of disease prevalence and low test sensitivity. Further studies are needed on the role of the AMPLICOR assay in better selected patients with an intermediate risk of having smear-negative PTB.

Adolescent↗

Audit of oxygen therapy in acute general medical wards following an educational programme.

INTRODUCTION: Previous studies have shown that the administration of supplementary oxygen (O2) in hospitalised patients outside the intensive care units (ICU) was usually empirical, inappropriate and not in compliance with physiological guidelines. It has been suggested that routine use of portable pulse oximeters in general wards plus in-service education of doctors and nurses may ameliorate this problem. MATERIALS AND METHODS: We introduced the use of pulse oximeters in general wards and instituted an educational programme on O2 therapy in a University Hospital. We then audited the process of O2 therapy in 100 consecutive adult medical inpatients. RESULTS: We found that, despite an educational programme and the easy availability of pulse oximeters, the quality of O2 therapy was poor. Half the patients did not receive objective pre-treatment assessment while 43% of patients were not adequately reassessed after O2 supplementation had been started. The most common error was excess use of O2 which occurred in 75% of patients. CONCLUSION: The quality of O2 therapy in the non-ICU setting was poor. Excessive O2 use was the most common error. We suggest that titration of O2 therapy, guided by pulse oximeter-guided protocols, may be needed to improve the quality and reduce the cost of O2 therapy in the hospital. This intervention may best be instituted within the environment of a continuous quality improvement model of health care delivery.

Adult↗

Human genetic susceptibility to tuberculosis.

INTRODUCTION: Recent advances in the understanding of human susceptibility to tuberculosis have resulted from the application of molecular techniques to answer mechanistic questions on genetic regulation of host defense. METHODS: This review is based upon a MEDLINE search of articles relevant to human genetic susceptibility to mycobacteria. RESULTS: The impact of natural selection in shaping susceptibility to infectious disease should be taken into account when different ethnic groups are compared. Molecular typing has improved the accuracy of HLA analysis. However, most of the recent advances have come from research in non-HLA genes. Multiple non-HLA genes controlling susceptibility to tuberculosis have been identified by family-based linkage studies and population-based case-control studies. Comparative genomic studies based upon a mice model have identified a new resistance-associated protein in human macrophages. Several rare inherited disorders of mycobacterial immunity are caused by isolated gene mutations in the interferon gamma-interleukin 12 pathways. Allelic variations in the vitamin D receptor have also been related to tuberculosis. A locus on human chromosome 17q have been linked to tuberculosis in a family-based genomic screening study. CONCLUSION: Susceptibility to tuberculosis involves large number genes inherited in a complex manner. Further discoveries are expected in the wake of rapid progress in the human genome project.

Animals↗

Relation between morbidity and current treatment in patients who present with acute asthma to polyclinics.

BACKGROUND: It has been suggested that resources for asthma intervention should be focused mainly on patients in the community who experience a high burden of disease. These are who patients who have acute exacerbations which require urgent treatment. AIM: To assess the morbidity and identify deficiencies in the treatment of patients who present for urgent treatment of acute exacerbations to primary care clinics. PATIENTS: Adult patients who received urgent treatment for acute exacerbation of bronchial asthma SETTING: 4 primary care polyclinics. METHODS: A cross-sectional survey of consecutive patients which related regular preventive treatment to current asthma activity. Poor asthma control was defined as step 2 or higher (American National Asthma Education and Prevention Program, report II, 1997) or > or = 2 emergency room visits in 6 months. RESULTS: There were 116 patients of whom 53% were women. The mean (SD) age was 45(15) years and duration of current exacerbation 3 (3) days. The acute symptoms were successfully treated in 93% of patients. Quick relief medication was used regularly in 91% and inhaled corticosteroids (ICS) in 55%. Oral salbutamol was prescribed in 14% of patients. The asthma was poorly controlled in 54%. In the poorly controlled group 33% were not on regular ICS treatment and 64% were not receiving "add on" medication. CONCLUSIONS: Patients treated for acute asthma in primary care clinics: (1) were older and had less acutely severe exacerbations than those who presented to emergency rooms, (2) over half had poorly controlled asthma and (3) a third of patients with poor asthma control were inadequately treated.

Acute Disease↗

The rapid diagnosis of smear-negative pulmonary tuberculosis: a cost-effectiveness analysis.

OBJECTIVE: The prompt diagnosis of smear-negative pulmonary tuberculosis (PTB) is a clinical challenge. It may be achieved by a number of tests which have varying accuracies, costs and degrees of invasiveness. The objective of this study was to compare the cost-effectiveness of clinical judgement (empirical), the Roche Cobas amplicor assay for Mycobacterium tuberculosis (amplicor), acid-fast staining of bronchoalveolar lavage specimens (BAL), nucleic acid amplification tests of bronchoalveloar lavage specimens for M. tuberculosis (BAL + NAA), computed tomography (CT) and amplicor assay followed by BAL. METHODOLOGY: The range of predictive values of the various strategies were derived from published data and a new study of 441 consecutive adult patients with suspected smear-negative PTB prospectively stratified into three pretest risk groups: low, intermediate and high. The cost-effectiveness was evaluated with a decision tree model (DATA software). RESULTS: The incidence of PTB was 5.7% (4% culture positive) for the whole group, 95% in the high-risk group, 0.9% in the low-risk group and 3.4% in the intermediate-risk group. The sensitivity of the empirical approach was 49% and of the amplicor assay was 44%. Patient outcomes were expressed as life expectancy for the base case of a 58-year-old man with a pretest probability of 5.7%. At this low pretest risk the differences in life expectancies between tests was < 0.1 years and the empirical approach incurred the lowest cost. Sensitivity analysis at increasing pretest risks showed better life expectancies (approximately 1 years) for CT scan and test combinations than empirical and amplicor for additional costs of US$243-US$309. Bronchoalveolar lavage had the worst overall cost-effectiveness. CONCLUSIONS: We conclude that the pretest risk of active PTB was a key determinant of test utility; that the AMPLICOR assay was comparable to clinical judgement; that BAL was the least useful test; and that with increasing risks, CT scan and test combinations performed better. Further studies are needed to better define patients with intermediate risk for PTB and to directly compare the cost-effectiveness of more sensitive nucleic acid amplification tests such as the enhanced Gen Probe, CT scan and test combinations/sequences in these patients.

Bacteriological Techniques↗

Asthma in the elderly--a more severe disease.

OBJECTIVE: To determine the severity of asthma in the elderly compared to the younger asthmatics. DESIGN: Cross-sectional study. SETTING: University outpatient asthma clinic. SUBJECTS: Asthmatics seen over a 6 month period in 1997. RESULTS: There were 154 patients and 16% were elderly (> 65 years) asthmatics. The elderly asthmatics were on significantly more anti-asthmatic medications (2.3 +/- 1.1 vs. 1.6 +/- 0.9, p < 0.001), and their clinical severity was significantly worse than their younger counterparts (Step 2.2 +/- 1.2 vs. 1.7 +/- 1.0, p < 0.001). Near-fatal asthma episodes were also more common in the elderly asthmatics (39% vs 13%, chi 2 test p < 0.01). CONCLUSIONS: Elderly asthmatics appear to have more severe asthma as evidenced by the increase in near-fatal episodes, and their increased clinical severity.

Adult↗

On-line high-performance liquid chromatography/mass spectrometric investigation of amyloid-beta peptide variants found in Alzheimer's disease.

Abeta peptides are the major components of amyloid deposits in Alzheimer's disease. The presence of N-terminally truncated Abeta variants in amyloid may be a critical factor in Alzheimer's disease pathogenesis. These Abeta variants are less soluble and more amyloidogenic than full-length Abeta, making their separation, purification and identification difficult. High-performance liquid chromatography (HPLC) at elevated temperatures, coupled to electrospray ionization (ES) mass spectrometry (MS), enables rapid separation and identification of N-terminally truncated Abeta variants. This methodology provides a potential tool for exploring the importance of these Abeta variants in both the pathogenesis and diagnosis of Alzheimer's disease.

Alzheimer Disease↗

Lymphangiomyomatosis: radiological and measured lung function deterioration after contrast-enhanced computed tomography.

Pulmonary lymphangiomyomatosis (LAM) is a rare disease of unknown aetiology which occurs exclusively in women, usually of reproductive age. The findings on CT and high-resolution CT (HRCT) are well described and characteristic, and in a young woman they are virtually pathognomonic. A case of symptomatic, radiological and measured lung function deterioration following contrast-enhanced CT in a patient with LAM are reported here. These observations, to the authors' knowledge, have never been reported before. The authors attempt to explain these observations based on the known pathology of LAM.

Adolescent↗

Recent advances in the management of pleural sepsis: what is the evidence?

The management of pleural sepsis involves early diagnosis, administration of appropriate antibiotics, recognition of poor prognostic features and timely intervention to drain the infected pleural space. Important recent advances in the management of pleural sepsis include better imaging techniques, the use of flexible image-guided drainage catheters, adjunctive intrapleural thrombolytic therapy and the introduction of interventional thoracoscopy. These advances have been augmented, in the past year, by results from prospective controlled studies comparing different therapeutic options. This review describes an evidence-based approach to the management of pleural sepsis which incorporates recent therapeutic advances.

Algorithms↗

Empirical treatment with fibrinolysis and early surgery reduces the duration of hospitalization in pleural sepsis.

The efficacy of three different treatment protocols was compared: 1) simple chest tube drainage (Drain); 2) adjunctive intrapleural streptokinase (IP-SK); and 3) an aggressive empirical approach incorporating SK and early surgical drainage (SK+early OP) in patients with pleural empyema and high-risk parapneumonic effusions. This was a nonrandomized, prospective, controlled time series study of 82 consecutive patients with community-acquired empyema (n=68) and high-risk parapneumonic effusions (n=14). The following three treatment protocols were administered in sequence over 6 years: 1) Drain (n=29, chest catheter drainage); 2) IP-SK (n=23, adjunctive intrapleural fibrinolysis with 250,000 U x day(-1) SK); and 3) SK+early OP (n=30, early surgical drainage was offered to patients who failed to respond promptly following initial drainage plus SK). The average duration of hospital stay in the SK+early OP group was significantly shorter than in the Drain and IP-SK groups. The mortality rate was also significantly lower in the SK+early OP than the Drain groups (3 versus 24%). It was concluded that an empirical treatment strategy which combines adjunctive intrapleural fibrinolysis with early surgical intervention results in shorter hospital stays and may reduce mortality in patients with pleural sepsis.

Adolescent↗

Cause, treatment and outcome of patients with life-threatening haemoptysis.

BACKGROUND: Massive haemoptysis is a life-threatening situation which requires immediate medical attention and intervention. We reviewed 23 patients with life-threatening haemoptysis to document the cause, describe the treatment of these patients and to determine which form of treatment had a better outcome. DESIGN: Retrospective case study. METHODS: Consecutive patients were reviewed and data collected for the underlying cause, treatment and outcome of patients with life-threatening haemoptysis. RESULTS: Out of 23 patients, nine patients had active pulmonary tuberculosis and nine patients had post-tuberculous lung disease. Fifteen patients underwent bronchial embolisation, one patient had surgical resection and seven patients had received medical treatment. Five patients required intubation. Bronchial embolisation was significantly better than medical treatment at immediate cessation of haemoptysis (p < 0.05). Three (13%) patients died from haemoptysis. Follow-up duration averaged 16 months. CONCLUSIONS: The most common causes of haemoptysis were pulmonary tuberculosis and post-tuberculous bronchiectasis. Urgent bronchial artery embolisation was better at immediate cessation of haemoptysis than medical treatment.

Adolescent↗