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Biomedical subjects

K W Tsang

Publications and source records attributed to K W Tsang.

At least 19 recordsLinked to original sources

Anti-inflammatory effects of high-dose montelukast in an animal model of acute asthma.

BACKGROUND: Asthmatic inflammation is mediated by a network of cytokines, chemokines and adhesion molecules. Corticosteroids are the only effective agents available to control asthmatic inflammation. We investigated the effect of high-dose montelukast (MK), a selective cysteinyl leukotriene receptor 1 antagonist, on mediators of airway inflammation. OBJECTIVE: The aim of this study was to determine the effect of a 3-day course of high-dose MK on mediators of airway inflammation induced by a single allergen challenge in sensitized mice. METHODS: Ovalbumin (OVA)-sensitized BALB/c mice were treated with 25 mg/kg of MK or saline intravenously for 3 days. On the third day, a single inhalation challenge with OVA was given. Cellular infiltration was assessed in the bronchoalveolar lavage (BAL) and in the lung. Expression of IL-4, IL-5, IL-13 and eotaxin in the BAL, and the lung was determined. Serum IL-5 and total IgE was measured. IL-5 and eotaxin mRNA expression in the lung was determined. Finally, eotaxin and VACM-1 expression in the lung was assessed by immunohistochemistry. RESULTS: MK reduced the number of eosinophils in the BAL by > 90%. There was also significant reduction in IL-5 in the BAL, lung and the serum, and IL-5 mRNA expression in the lung. IL-4 level in the lung and BAL, and IL-13 level in the lung also significantly decreased. Serum IgE level and lung VCAM-1 expression was also significantly lower in treated animals, but eotaxin protein and mRNA expression in the lung remained unchanged. CONCLUSION: MK exerts its anti-inflammatory effect through the suppression of T helper type-2 (Th2) cytokines. The use of high-dose MK as an anti-inflammatory agent in acute asthma should be further explored.

Acetates↗

Down-regulation of aquaporin 3 in bronchiectatic airways in vivo.

Bronchiectasis is characterized pathologically by permanent abnormal bronchial dilation, and clinically by chronic sputum production. Aquaporin 3 (AQP3), a recently described water channel that is also found in large airway cell membrane, could play a role in the pathogenesis and particularly that of bronchorrhea in bronchiectasis. However, little is known of its in vivo distribution and physiological role in human airways. We have, therefore, performed this quantitative immunohistochemistry study on endobronchial biopsies to evaluate the expression and clinical relevance of AQP3 in patients with idiopathic bronchiectasis (n = 25, 15 F, 64.3 +/- 11.5 years) and control subjects (n = 14, 5 F, 57.5 +/- 12.0 years). Quantitative image analysis was performed to evaluate the expression of AQP3 in the bronchial epithelial cells. Our results show that AQP3 was predominantly expressed in the basal cells of the epithelial layer in both groups. Expression of AQP3 was significantly reduced in the basal, but not columnar, epithelial cells in bronchiectasis compared with control airways (p = 0.02, 0.35). Only bronchiectatic patients with regular sputum production, but not their counterparts, had significant downregulation of epithelial AQP3 expression compared with control airways (p = 0.004, 0.24). Our findings suggest that AQP3 could have an important role in the pathogenesis of increased mucus production in bronchiectasis.

Aquaporin 3↗

Coriolus versicolor polysaccharide peptide slows progression of advanced non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths, and over 60% of patients present with advanced stages. Although polysaccharide peptides (PSP), isolated from the fungus Coriolus versicolor, have been reported to have anti-tumor effects, its clinical efficacy has not been properly evaluated. METHODS: Double-blind placebo-controlled randomized study to evaluate the effects of 28-day administration of PSP (Windsor Pharmaceutical, Hong Kong) on patients, who had completed conventional treatment for advanced NSCLC. RESULTS: Thirty-four patients, with no significant difference in their baseline demographic, clinical or tumor characteristics, or previous treatment regimes (P>0.05) were recruited into each of the PSP and control arms. After 28-day treatment, there was a significant improvement in blood leukocyte and neutrophil counts, serum IgG and IgM, and percent of body fat among the PSP, but not the control, patients (P<0.05). Although the evaluable PSP patients did not improve in NSCLC-related symptoms, there were significantly less PSP patients withdrawn due to disease progression, than their control counterparts (5.9 and 23.5%, respectively; P=0.04; OR 4.00). There was no reported adverse reaction attributable to the trial medications. CONCLUSION: PSP treatment appears to be associated with slower deterioration in patients with advanced NSCLC.

Adult↗

Multiple brain abscesses in a patient with bilateral pulmonary arteriovenous malformations and immunoglobulin deficiency.

A 34 year old Chinese man presented with grand mal seizures complicating multiple brain abscesses caused by mixed oral flora. Because of persistent hypoxaemia contrast spiral thoracic computed tomography was done, which revealed bilateral pulmonary arteriovenous malformations (PAVMs). Concomitant IgA and IgG subclass deficiency was also found. The combination of these two conditions appears to have predisposed this patient to presumably paradoxical septic embolism. The patient's cerebral condition responded to postoperative antibiotic treatment and he eventually received selective coil embolisation of right lower lobe PAVMs, which relieved his hypoxaemia and dyspnoea.

Adult↗

Effects of erythromycin on Pseudomonas aeruginosa adherence to collagen and morphology in vitro.

The airways of patients with bronchiectasis and cystic fibrosis are often chronically colonised by Pseudomonas aeruginosa (PA), which is virtually impossible to eradicate. Low-dose erythromycin (EM), for unknown mechanisms, is efficacious in bronchiectasis and diffuse panbronchiolitis. In this study, an in vitro model to investigate PA adherence to human type IV basement collagen was developed by using scanning electron microscopy (SEM). There were significantly less PA bacilli per 20 random SEM fields (4,000x) when PA was cultured in 0.05, 0.5 and 5 microg x mL(-1) of EM compared with control (absence of EM). Adherence density (20 SEM fields x log(-1) inocular size) for PA obtained from no EM (56.8 +/- 43.16) was significantly higher than that obtained from 0.05, 0.5, and 5 microg x mL(-1) EM (21.5 +/- 17.56, 23.3 +/- 16.65, and 21.4 +/- 12.65 respectively). By using SEM it was found that PA, when incubated in EM (0.05, 0.5, 5 microg x mL(-1)) had a significant reduction in its diagonal length, radius, height, volume and surface area. It is possible, therefore, that these misshaped Pseudomonas aeruginosa bacilli are more susceptible to host defence mechanisms, while at the same time less adherent to the basement membrane of the airway in vivo. Therefore, this could help explain the clinical efficacy of low-dose erythromycin therapy on patients with Pseudomonas aeoruginosa infection.

Bacterial Adhesion↗

Pseudomonas aeruginosa adherence to human basement membrane collagen in vitro.

The mechanisms for Pseudomonas aeruginosa colonisation in the airways of patients with bronchiectasis and cystic fibrosis are poorly understood. P. aeruginosa could evade mucociliary clearance by adhering to the basement membrane at areas denuded of intact respiratory epithelium. The authors have developed an in vitro model to study P. aeruginosa adherence to human basement membrane type-IV collagen by using scanning electron microscopy. P. aeruginosa adherence density was determined as the number of P. aeruginosa per 20 microscope fields (2,000x) to log inocular size after incubation at 37 degrees C for 45 min. The presence of phytohaemagglutinin (PHA)-E, which binds specifically to D-galactose-beta1-4-D-N-acetylglucosamine, significantly reduced P. aeruginosa adherence density compared with control. The presence of heparin and calcium also significantly reduced P. aeruginosa adherence density. P. aeruginosa adherence was not affected by the presence of proline, trans-hydroxyproline, glycine, galactose, N-acetylneuraminic acid, N-acetylglucosamine or Arachis hypogea. Pseudomonas aeruginosa adherence probably acts via recognition of the D-galactose-beta1-4-D-N-acetylglucosamine sequence on type-IV collagen and this process could be inhibited by heparin and calcium. As persistent Pseudomonas aeruginosa colonisation is detrimental to patients with cystic fibrosis and bronchiectasis and there is currently no effective treatment for its eradication, these results could lead to novel therapy for persistent Pseudomonas aeruginosa infection.

Amino Acids↗

Severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a new disease that poses a threat to international health. The SARS epidemic earlier this year affected more than 30 countries and regions, with a cumulative global total of 8098 cases. It is caused by a novel coronavirus, probably of animal origin. The mean incubation period is 6.4 days (range 2-11 days). Patients usually present with high fever, chills, myalgia and dry cough, with or without chest X-ray evidence of pneumonia at the onset of disease. A history of contact with or travel to an area with local transmission is common. Diagnosis is based on clinical criteria, as a valid rapid diagnostic test is not yet available. There is no specific antiviral therapy for this disease, and no controlled clinical trial for any treatment modality has been conducted. In several retrospective studies steroids have been shown to be useful in a proportion of patients who deteriorated despite antibiotics and supportive treatment. SARS has a high morbidity (about 25% required intensive care) and fatality (9.6%). A high index of suspicion for the disease, isolation of patients, strict observation of infection control practices and compliance with use of personal protective equipment are necessary to prevent nosocomial infection. Contact tracing and quarantine are essential measures to prevent community spread of disease. Prevention of future outbreaks requires strengthening of infection control practices in hospitals, development of a rapid diagnostic test and a vaccine, and removal of any animal reservoir and environmental conditions that led to the spread of the disease.

Adolescent↗

Overexpression of matrix metalloproteinase-8 and -9 in bronchiectatic airways in vivo.

The progressive bronchial dilatation in bronchiectasis is likely to be the result of continued airway matrix destruction, although little is known about the role of neutrophil matrix metalloproteinases (MMPs) in this process. Immunohistochemistry has been used to investigate the expression and cellular localisation of MMP-8 and MMP-9 in bronchiectatic airways in vivo. Endobronchial biopsies were taken from 25 bronchiectatic patients, and from the right lower lobe in 14 control subjects. MMP-8, MMP-9, neutrophils and macrophages were stained with monoclonal antibodies and quantified as positive cell x mm(-2) of the lamina propria by using an image analysis system. There were significantly higher densities of MMP-8 and MMP-9 positive cells in the lamina propria of bronchiectatic than control airways. In bronchiectatic airways, the densities of MMP-8 and MMP-9 positive cells correlated with each other and with neutrophil density, but not with macrophage density. In control airways, a significant correlation was found between MMP-8 with neutrophil and MMP-9 with macrophage densities. An overexpression of neutrophil matrix metalloproteinases in bronchiectatic airways could help explain the continuation of airway destruction in bronchiectasis. In view of the clinical availability of matrix metalloproteinase antagonists, the results presented here could have a significant impact on the development of novel therapies of this untreatable disease.

Aged↗

Pulmonary sequelae of treatment for breast cancer: a prospective study.

PURPOSE: To prospectively study the effects of loco-regional radiotherapy in women with breast cancer. METHODS AND MATERIALS: Thirty consecutive patients with breast resection underwent clinical, lung function, radiographic, and thoracic high-resolution computed tomography evaluation before and at 1, 3, 6, and 12 months after adjuvant radiotherapy. Chemotherapy was also administered to 15 patients. RESULTS: Nineteen patients reported mild respiratory symptoms at 1 month, which resolved completely at 6 months after radiotherapy. Opacities were present on 80% of chest radiographs and in all patients on high-resolution computed tomography by 3 months. These opacities became compact and persisted on high-resolution computed tomography at 12 months. Lung function indices, including FEV1, FVC, TLC, and DLCO, progressively declined after radiotherapy, and was irreversible at 12 months (p < 0.05). Patients who received chemotherapy did not have significantly different lung function indices compared with their counterparts at all time points (p > 0.05). CONCLUSIONS: Our results have shown that adjuvant loco-regional radiotherapy, a common practice in breast cancer treatment, is associated with irreversible reduction in lung function parameters. These changes are accompanied by radiological evidence of persistent lung injury. Further studies should be performed to evaluate the incidence and long-term pulmonary sequelae of current treatment for breast cancer.

Adult↗

Risk factors for acquisition of levofloxacin-resistant Streptococcus pneumoniae: a case-control study.

A case-control study was conducted to identify the risk factors associated with levofloxacin-resistant Streptococcus pneumoniae (LRSP) colonization or infection. Twenty-seven case patients (patients with LRSP) were compared with 54 controls (patients with levofloxacin-susceptible S. pneumoniae). Risk factors that were significantly associated with LRSP colonization or infection, according to univariate analysis, included an older age (median age, 75 years for case patients versus 72.5 years for controls), residence in a nursing home (odds ratio [OR], 7.2), history of recent (OR, 4.6) and multiple (OR, 4.4) hospitalizations, prior exposure to fluoroquinolones (OR, 10.6) and beta-lactams (OR, 8.6), presence of chronic obstructive pulmonary disease (COPD; OR, 5.9), and nosocomial origin of the bacteria (OR, 5.7). Multivariate analysis showed that presence of COPD (OR, 10.3), nosocomial origin of the bacteria (OR, 16.2), residence in a nursing home (OR, 7.4), and exposure to fluoroquinolones (OR, 10.7) were independently associated with LRSP colonization or infection. Thus, a distinct group of patients with COPD is the reservoir of LRSP.

Aged↗

Exhaled nitric oxide: the effects of age, gender and body size.

Since little is known of the effects of age, gender, and body size on exhaled nitric oxide (NO) production, we have conducted a prospective study to examine these factors in a healthy nonsmoking women (mean age +/- SD 47.7 +/- 15.8, range 20-79 years). Exhaled NO was measured by an automatic chemiluminescence analyzer (Sievers NO Analyser 280) at steady expiration. Men had significantly higher exhaled NO levels than women (p = 0.001). Although exhaled NO levels did not correlate with age (r = 0.12, p = 0.17), it correlated significantly with height (r = 0.23, p = 0.02), weight (r = 0.34, p

Adult↗

Respiratory ciliary function in bone marrow recipients.

Bone marrow transplantation (BMT) recipients, particularly those with chronic graft-versus-host disease (GVHD), suffer from respiratory tract problems, including bronchiolitis obliterans (BO) and recurrent lower respiratory tract infections. Minute cilia beat continuously on the surface of respiratory mucosa, and this beating maintains the sterility of the lower respiratory tract. Dysfunction of respiratory cilia could lead to development of recurrent respiratory tract infections, which are also features of BMT recipients, although ciliary function has not been systematically studied among these subjects. We have, therefore, investigated the ciliary beat frequency (CBF) of 36 Chinese patients who had undergone allogeneic BMT. The CBF was significantly lower in the BMT group compared to controls (P < 0.001). The reduction in CBF was more severe in patients with cGVHD and BO compared with their counterparts (P = 0.048 and P = 0.077, respectively). There was a correlation between CBF with forced expiratory flow rate FEF (P = 0.024) and forced expiratory volume FEV (P = 0.044). We conclude that abnormal ciliary clearance is a common feature after allogeneic BMT, particularly among patients with BO and cGVHD. Further studies are indicated to evaluate this important phenomenon, which could be an important cause of the susceptibility for BMT recipients to respiratory infections.

Adolescent↗

Pulmonary cryptococcosis: a case report and review of the Asian-Pacific experience.

Pulmonary cryptococcosis is a very rare form of pneumonia, which is seldom seen among immunocompetent patients. We report the case of a 36-year-old man who presented with indolent pneumonia that was subsequently diagnosed to be pulmonary cryptococcosis without other systemic involvement. Contrary to formal belief, there was evidence of residual lung fibrosis 12 months after initial presentation. The features of pulmonary cryptococcosis reported in the Asian Pacific region are also reviewed.

Adult↗

Macrophages, neutrophils and tumour necrosis factor-alpha expression in bronchiectatic airways in vivo.

Bronchiectasis is increasingly being recognized as an inflammatory condition of the airways in which pathological permanent dilation occurs. We have obtained endobronchial biopsies in 14 patients with stable bronchiectasis and 15 control subjects. Airway neutrophils, macrophages and tumour necrosis factor-alpha (TNFalpha)-positive cells were stained with monoclonal antibodies and the densities of positive cells in the lamina propria were determined by using a computer image analyser. There was significantly higher neutrophil, macrophage and TNFalpha-positive cell densities in the lamina propria of bronchiectatic than control airways (P < 0.001, P < 0.001 and P=0.0002, respectively). Airway neutrophil density in bronchiectasis but not in controls, correlated with TNFalpha-positive cell density (r=0.71, P=0.004). A significant correlation between airway macrophage and TNFalpha-positive cell densities was demonstrated in both control and bronchiectatic airways (r=0.63, P=0.016 and r=0.60, P=0.02 respectively). Neutrophil density negatively correlated with per cent forced vital capacity (FVC%) predicted among patients with bronchiectasis (r=-0.53, P=0.04). Bronchiectasis patients who were regular sputum producers had a significantly higher macrophage, but not neutrophil density than their counterparts (P=0.02 and P=0.48 respectively). Our original findings suggest that airway macrophages could contribute to neutrophil influx into airway walls through their production of TNFalpha and therefore play an important role in the pathogenesis of bronchiectasis.

Aged↗

Adenocarcinoma of the lung in Chinese patients: a revisit and some perspectives from the literature.

AIM: To establish an updated clinical profile of adenocarcinoma of the lung. DESIGN: Retrospective review of clinical charts, chest radiography, and computed tomography of consecutive patients who attended Queen Mary Hospital in Hong Kong between June 1995 and December 1997. RESULTS: In the 115 patients studied, 13% were <40 years of age (33.3% ever smokers). Haemoptysis is more common among patients with early disease, while finger clubbing was detected more commonly among smokers and ex-smokers. Most (98.3%) patients had abnormal chest radiology including presence of mass lesion, pleural effusion, collapse/consolidation, and effusion. Patients with adenocarcinoma were significantly more likely to be younger, female, in advanced disease (stage IIIB and IV), non-smoker, and symptomatic on presentation (p<0.05) than those with squamous cell lung cancer (n=128). CONCLUSION: The clinical profile of Chinese adenocarcinoma patients should help clinicians in the diagnosis and management of these patients.

Adenocarcinoma↗

Solutions for difficult diagnostic cases of acute exacerbations of chronic bronchitis.

Acute exacerbation of chronic bronchitis (AECB) is a very common condition, which presents with deteriorating sputum production and dyspnoea in a patient with pre-existing COPD or chronic bronchitis. As these symptoms are relatively non-specific and also the presenting feature of a wide range of other conditions, the physician should carefully consider the differential diagnosis before deciding on whether or not a patient indeed has AECB. The differential diagnosis can be summarised as pneumonia, pneumothorax, cardiac failure/cor pulmonale, bronchiectasis, asthma, tuberculosis, sinusitis and other forms of upper respiratory tract sepsis, diffuse panbronchiolitis, lung cancer, gastro-oesophageal reflux, the presence of a foreign body in the airway, melioidosis, and lung abscess. This article aims to discuss these conditions, with brief presentation of clinical cases, in the evaluation of differential diagnosis of AECB.

Bronchitis, Chronic↗

The effect of aging on nasal mucociliary clearance, beat frequency, and ultrastructure of respiratory cilia.

The increased susceptibility of the elderly to lower respiratory tract infection cannot be fully explained. Although mucociliary clearance, which is affected by ciliary beating and ultrastructure, plays a crucial role in the defense of the airways against inhaled microbes, little is known of the effects of aging on these parameters. We studied the nasal mucociliary clearance (NMCC) time, ciliary beat frequency, and ultrastructure of respiratory cilia in a cohort of healthy volunteers (age range 11 to 90 yr). Ciliary beat frequency of ciliated nasal epithelial cells was obtained via an established photometric method, and NMCC time was measured with the saccharine test. There was a correlation of ciliary beat frequency (r = -0.48, p = 0.0001) and NMCC time r = 0.64, p < 0.001) with increasing age. Transmission electron microscopy revealed an increase in the percent of subjects exhibiting microtubular disarrangement and single central microtubules with aging (p = 0.002 and p = 0.005, respectively). Subjects older than 40 yr of age had significantly slower ciliary beat frequency, higher percent of ciliary cross-sections displaying single tubules, and longer NMCC time than their younger counterparts (p < 0.05). These findings may help explain the frequent occurrence of respiratory infection in the elderly.

Adolescent↗