Biomedical subjects

W K Lam

Publications and source records attributed to W K Lam.

At least 37 records · Page 2Linked to original sources

PubMed2003

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the evaluable PSP patients did not improve in NSCLC-related symptoms, there were significantly less PSP patients withdrawn due to disease progression, than their control counterparts (5.9 and 23.5%, respectively; P=0.04; OR 4.00).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↗

PubMed2003

Interstitial lung disease in systemic sclerosis.

PURPOSE: To evaluate high-resolution CT (HRCT) parameters of inflammation and fibrosis in systemic sclerosis (SSc), for correlation with lung function, skin scores and exercise tolerance. MATERIAL AND METHODS: 45 SSc patients (40 women, 48.5+/-13.4 years), underwent thoracic HRCT, lung function assessment, and modified Rodnan skin scores. Exercise tolerance was also graded. HRCT were scored for extent of 4 HRCT patterns of interstitial lung disease (ILD): ground glass opacification (GGO), reticular, mixed and honeycomb pattern in each lobe. Total HRCT score, inflammation index (GGO and mixed score) and fibrosis index (reticular and honeycomb scores) were correlated with lung function and clinical parameters. RESULTS: ILD was present in 39/45 (86.7%) patients. Abnormal (<80% predicted) forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusion factor (DLco) were detected in 30%, 22% and 46% of patients. Total HRCT score correlated with FVC (r=-0.43, p=0.008), FEV1 (forced expiratory volume) (r=-0.37, p=0.03), TLC (r=-0.47, p=0.003), and DLCO (r=-0.43, p=0.008); inflammatory index with DLCO (r=-0.43, p=0.008) and exercise tolerance (r=-0.39, p < 0.05); and fibrosis index with FVC (r=-0.31, p=0.05) and TLC (r=-0.38, p=0.02). Higher total HRCT score, and inflammation and fibrosis indices were found in patients with abnormal lung function. CONCLUSION: Qualitative HRCT is able to evaluate inflammation and fibrosis, showing important relationships with diffusion capacity and lung volume, respectively.

Exercise Tolerance↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2003

Lymphoepithelioma-like carcinoma of the lung in a patient with silicosis.

Silicosis is an important form of pneumoconiosis, which is caused by significant exposure to crystalline silica. The carcinogenicity of silica, despite traditional beliefs, in relation to lung cancer has been controversial. Lymphoepithelioma-like carcinoma of the lung, an Epstein-Barr virus-associated undifferentiated carcinoma, is a rare entity of pulmonary malignancy, which tends to affect young nonsmoking Asians. The first case of silicosis, initially complicated by pulmonary tuberculosis, which later developed into advanced lymphoepithelioma-like carcinoma of the lung is reported. A combination of 5-fluorouracil, cisplatin and calcium folinate resulted in partial tumour response.

Aged↗

PubMed2002

Computed tomography characteristics of advanced primary pulmonary lymphoepithelioma-like carcinoma.

Our objectives were to document CT features of advanced primary pulmonary lymphoepithelioma-like carcinoma (LELC) and to determine features that may assist differentiation from other non-small cell lung cancers (NSCLC). Imaging and clinical data of all patients with biopsy-proven pulmonary LELC ( n=12) were retrieved from a database of all NSCLC patients over a 2-year period. Twenty-five controls were recruited from other inoperable non-LELC NSCLC patients from the database. Pre-treatment CT scans of the thorax of both study and control patients were reviewed for lobe involved; tumour site, borders and size; and pleural, vascular or pulmonary involvement. Presence of lymphangitis carcinomatosis was noted. Lymph node metastasis was characterised as ipsilateral or contralateral enlarged (>1 cm) mediastinal or hilar nodes, or as peribronchovascular nodal spread. Differences between the two groups were tested using Mann-Whitney rank-sum test. The LELC tumours were significantly larger (45.67 vs 17.71 cm(2)) than controls and were closely associated with the mediastinum. There were more LELC tumours with well-defined borders ( p<0.001) and fewer with spiculated borders ( p<0001) than non-LELC tumours. There was increased peribronchovascular nodal spread ( p=0.01) and vascular encasement ( p=0.02) in LELC compared with non-LELC tumours. Advanced primary pulmonary LELC has distinct radiological features, and can appear as well-defined tumour closely associated with the mediastinum, with peribronchovascular spread and vascular encasement.

Adenocarcinoma↗

PubMed2002

Pulmonary iron overload in thalassemia major presenting as small airway disease.

Lung function abnormalities that are associated with thalassemia major are variable with etiology that is yet undetermined. Some studies have suggested that pulmonary iron deposition is a probable cause for these lung defects although there has been no antemortem histopathological and radiological evidence for this. We report a case of thalassemia major with biopsy-proven pulmonary iron overload, in which thoracic high-resolution computed tomography revealed a morphological-functional correlation consistent with small airway disease.

Adult↗

PubMed2002

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↗

PubMed2001

Temporal and spatial overlap between monarch larvae and corn pollen.

To assess the likelihood that monarch larvae will be exposed to Bacillus thuringiensis (Bt) pollen, we studied milkweed and monarch densities in habitats which comprise much of the land available to breeding monarchs, e.g., cornfields, cornfield edges, other agricultural fields, and nonagricultural areas, in four regions of the monarch breeding range. We found that monarchs use milkweed in cornfields throughout their breeding season, and that per plant densities are as high or higher in agricultural habitats as in nonagricultural habitats. As a result of the prevalence of agricultural land, most of the monarchs produced in the upper Midwest are likely to originate in cornfields or other agricultural habitats. There was a greater temporal overlap between susceptible monarchs and corn anthesis in the northern than the southern part of the summer breeding range, because of earlier pollen shed in the south. The importance of agricultural habitats to monarch production suggests that, regardless of the impact of genetically modified crops, agricultural practices such as weed control and foliar insecticide use could have large impacts on monarch populations.

Animals↗

PubMed2001

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↗

PubMed2001

Genomic imprinting and cancer; new paradigms in the genetics of neoplasia.

The role of epigenetic modification of gene expression is becoming increasingly important in how we understand the loss of tumour suppressor gene function in a variety of tumours and tumour predisposing syndromes. This review explores the importance of epimutation in Beckwith-Wiedemann syndrome and Wilms' tumour and focuses on genomic methylation in both imprinted and non-imprinted genes as a key mechanism in the development of cancer.

Aging↗

PubMed2001

Development of a Marine Sediment Pollution Index.

To facilitate translation of the state of marine sediment quality for public information, a pollution index was developed from the results of a routine monitoring program. Principal component analysis (PCA) of 24 variables at 64 monitoring stations from 1987 to 1997 was carried out to identify the most important parameters that were applied in the index formulation. Of the 24 variables, six (Cr, Cu, Ni, chemical oxygen demand, Zn, Mn) were selected on the basis of their high PCA loadings. The derived Marine Sediment Pollution Index, rating from 0 to 100, reflected the general trend in the monitoring areas. The index was also found to have a significant negative correlation (P < 0.05) with the benthic species diversity and toxicity of the sediment, indicating its usefulness in reflecting marine sediment quality. The application of PCA to identify important variables from a monitoring program would reduce sampling resources, as parameters that did not show significant spatial or temporal variations could be analyzed in a lesser frequency than those that were identified to be more important from the results of PCA.

Animals↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

Lack of inducible nitric oxide synthase promotes intestinal tumorigenesis in the Apc(Min/+) mouse.

BACKGROUND & AIMS: The role of the inducible isoform of nitric oxide synthase (Nos2 or iNOS) in intestinal tumorigenesis is unclear. Conflicting data also exist regarding the ability of Nos2 to modulate expression and/or activity of cyclooxygenase 2 (Cox-2), which promotes intestinal tumorigenesis. Therefore, we determined the effect of a null Nos2 genotype on intestinal tumorigenesis and Cox-2 expression/activity in the Apc(Min/+) mouse model of familial adenomatous polyposis. METHODS: Apc(Min/+)Nos2(-/-) mice were generated by successive crosses between C57BL/6-Apc(Min/+) and C57BL/6-Nos2(tm1Lau) mice. Adenoma characteristics of age-matched Apc(Min/+)Nos2(+/+) and Apc(Min/+)Nos2(-/-) mice were compared. The level and cellular localization of Nos2 messenger RNA (mRNA) expression in Apc(Min/+)Nos2(+/+) mouse intestine was determined. Cox-2 expression and activity were measured in both intestinal tissue and bone marrow-derived macrophages in vitro. RESULTS: Apc(Min/+)Nos2(-/-) mice developed significantly more intestinal adenomas than Apc(Min/+)Nos2(+/+) littermates. Epithelial cell Nos2 mRNA expression was decreased in adenomas compared with histologically normal Apc(Min/+)Nos2(+/+) intestine. There was no significant difference in Cox-2 expression or activity in either intestine or bone marrow-derived macrophages from Apc(Min/+)Nos2(+/+) and Apc(Min/+)Nos2(-/-) animals. CONCLUSIONS: Nos2 plays an antineoplastic role in the Apc(Min/+) mouse model of familial adenomatous polyposis. Nos2 does not modulate Cox-2 expression or activity in the Apc(Min/+) mouse.

Adenomatous Polyposis Coli Protein↗

PubMed2001

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↗

PubMed2001

Effects of dexamethasone on the expression of Fas molecules and apoptosis of lymphocytes in patients with systemic lupus erythematosus.

Previous studies have shown that the autoimmune phenomenon could be caused by defective apoptosis of autoreactive lymphocytes. Corticosteroids used for treatment of systemic lupus erythematosus (SLE) are potent apoptosis inducers. We examined dexamethasone (DEX)-induced apoptosis and Fas expression in peripheral blood lymphocytes of SLE patients and normal subjects. Peripheral blood lymphocytes were obtained from 40 SLE patients and 18 sex- and age-matched control subjects. Percentages of apoptosis and expression of Fas molecule in lymphocytes were assessed by flow cytometry. Fas expression in lymphocytes treated with or without DEX was significantly higher in SLE patients than normal controls [median (interquartile range) of mean fluorescence intensity without DEX: 74.9 (50.7-98.0) vs 20.0 (17.7-25.0), p < 0.001; with DEX: 77.9 (56.0-130.5) vs 20.5 (18.6-24.7), p<0.001]. DEX (0.1-5 microM) could also induce apoptosis of lymphocytes from SLE and control subjects in a dose-dependent manner. Elevation of apoptotic susceptibility was more prominent in DEX-treated SLE lymphocytes [33.9% (24.7-37.5%) vs 19.6% (13.6-26.1 %), p = 0.003]. The higher apoptotic susceptibility of SLE lymphocytes upon DEX treatment in vitro may be related, at least partly, to the pharmacological action of corticosteroids.

Adolescent↗

PubMed2001

Increasing use of inhaled steroids associated with declining asthma mortality.

Increasing worldwide asthma prevalence and mortality has led to greater advocacy of inhaled agents, especially steroids. To determine whether corresponding drug usage trends had ensued locally, wholesale data (expressed as defined daily doses (DDDs)/1000 inhabitants/day) were compared for inclusive periods 1984-1986 and 1992-1994. Whereas absolute usage of anti-asthmatics increased by 79%, proportional inhaled usage increased markedly, especially of steroids (571%) and in hospitals. An odds ratio trend analysis revealed asthma mortality from 1992 onward had declined, particularly in males (p < 0.001). In Hong Kong, despite increasing asthma prevalence, more intensive use of anti-asthmatic drugs (especially inhaled steroids) was associated with declining asthma mortality.

Administration, Inhalation↗