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Biomedical subjects

W K Lam

Publications and source records attributed to W K Lam.

At least 19 recordsLinked to original sources

Disturbance of systemic antioxidant profile in nonsmall cell lung carcinoma.

The present study aimed to determine the alterations of antioxidant activities in erythrocytes from patients with nonsmall cell lung carcinoma (NSCLC). A comparative study of the systemic antioxidant activities in red blood cell lysate from subjects with NSCLC and healthy control subjects was conducted. The antioxidants catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured using chemical kinetic reactions under spectrophotometry. In total, 189 cases of mostly advanced-stage IIIB or stage IV NSCLC and 202 healthy controls were studied. In subjects with lung cancer, there was similar catalase activity, lower SOD activity (median (interquartile range) 13.4 (9.0-27.2) versus 48.7 (27.0-64.3) U x (ghaemoglobulin(Hb)(-1)), and higher GPx activity (175.2 (126.6-288.3) versus 49.2 (39.5-59.2) mU x (gHb)(-1)) compared with controls. The antioxidant activities in lung cancer subjects were not associated with age, sex, smoking status, or tumour cell types. However, more advanced disease (stage IV compared with stage IIIB) was associated with lower SOD activity. Using multivariable analysis, the presence of lung cancer independently predicted SOD and GPx activities. In conclusion, nonsmall cell lung carcinoma in Chinese subjects is associated with alterations in systemic antioxidant activities, which may play an important role in carcinogenesis.

Adult↗

The clinical value of autofluorescence bronchoscopy for the diagnosis of lung cancer.

The aim of this study was to evaluate the role of autofluorescence bronchoscopy (AFB) in the routine work-up of lung cancer. Consecutive patients with atypical or suspicious cells in sputum or bronchial aspirate, no localising abnormality on chest radiography and nondiagnostic white-light bronchoscopic (WLB) results were recruited. WLB and AFB were performed sequentially during the same session. All abnormal areas detected by WLB, AFB or both were sampled and the biopsy specimens sent for histological examination. Sixty-two patients were recruited within the 32-month study period. Seventeen had no endobronchial lesion detected. Among the 45 patients with endobronchial lesions, 37 had lesions with a histopathological grade of mild dysplasia or less; of the eight patients who had a lesion with a histological grade of moderate dysplasia or worse, five were found to have lung cancer, two invasive lung cancer and three an intra-epithelial neoplasm (severe dysplasia). Lesions showing moderate dysplasia or worse were more commonly found in patients with suspicious cells than in those with atypical cells on sputum examination. AFB was more sensitive than WLB (91 versus 58%) at detecting these lesions, but less specific (26 versus 50%). A combination of white-light and autofluorescence bronchoscopy can increase the diagnostic yield of this invasive procedure in patients exhibiting abnormal sputum cytology.

Adult↗

A prospective study of respiratory ciliary structure and function after stem cell transplantation.

We prospectively investigated the morphological and ciliary function abnormalities in 19 consecutive Chinese patients undergoing hemopoietic stem cell transplantation (HSCT) and studied their relationship with pulmonary complications. The percentage of structural ciliary abnormalities preceding HSCT was comparable to normal controls, but increased up to 1-year post-HSCT. However, the abnormalities did not correlate with ciliary or pulmonary function. Ciliary beat frequency (CBF) for patients undergoing autologous and allogeneic SCT was lower than that of matched controls, with a further decline at one year. There was, however, no significant change in pulmonary function for the whole cohort. There was considerable variation in CBF and ciliary abnormalities in all cases during 3-month interval assessments. Regular ciliary assessment did not predict the only two patients who eventually suffered from bronchiolitis obliterans (BO). We conclude that structural and functional ciliary abnormalities are common in recipients of HSCT, and predict post-HSCT deterioration. However, there is no evidence to show that CBF monitoring may be of prospective benefit.

Adult↗

Recurrent pneumothorax in pregnancy: what should we do after placing an intercostal drain.

Recurrent pneumothorax is rare during pregnancy. We describe a Chinese woman, with a history of spontaneous pneumothorax managed with an intercostal drain, who developed a recurrent pneumothorax during her 32nd week of pregnancy. There is no consensus on management in this situation. We review the literature and discuss different management approaches. Thirty-six cases of antepartum pneumothorax have been reported in 31 case reports. An intercostal drain only (n=11) or surgeries (thoracotomy, n=9; or video-assisted thoracoscopy, n=2) were common treatment options with no surgical complications reported. Twenty-two (61%) patients progressed to a normal vaginal delivery, while the rest required forceps delivery (22%) or Caesarean section (14%). No single treatment option outweighed the others. There were no maternal or foetal complications reported in those who underwent antepartum surgical intervention. Surgical management of recurrent pneumothorax during pregnancy is well tolerated.

Adult↗

Conserved transcription factor binding sites of cancer markers derived from primary lung adenocarcinoma microarrays.

Gene transcription in a set of 49 human primary lung adenocarcinomas and 9 normal lung tissue samples was examined using Affymetrix GeneChip technology. A total of 3442 genes, called the set M AD, were found to be either up- or down-regulated by at least 2-fold between the two phenotypes. Genes assigned to a particular gene ontology term were found, in many cases, to be significantly unevenly distributed between the genes in and outside M AD. Terms that were overrepresented in M AD included functions directly implicated in the cancer cell metabolism. Based on their functional roles and expression profiles, genes in M AD were grouped into likely co-regulated gene sets. Highly conserved sequences in the 5 kb region upstream of the genes in these sets were identified with the motif discovery tool, MoDEL. Potential oncogenic transcription factors and their corresponding binding sites were identified in these conserved regions using the TRANSFAC 8.3 database. Several of the transcription factors identified in this study have been shown elsewhere to be involved in oncogenic processes. This study searched beyond phenotypic gene expression profiles in cancer cells, in order to identify the more important regulatory transcription factors that caused these aberrations in gene expression.

5' Flanking Region↗

Violence against substance-abusing South African sex workers: intersection with culture and HIV risk.

The Republic of South Africa has become an epicentre of heterosexual HIV transmission among Black women, and the interface between violence against women, substance abuse, and HIV risk is becoming evident. This paper describes the characteristics of Black South African women who engage in sex work in Pretoria and examines their intersecting experiences of high-risk sexual behaviour, substance abuse, and victimization. Ninety-three women were recruited into the study. Field staff collected biological measures of drug use and administered a structured, self-report interview. Findings indicate that young South African women who engage in sex work and use drugs rely on this activity as their main source of income and are supporting other family members. The majority of sample women reported experiencing some victimization at the hand of men, either clients or boyfriends, with many reporting childhood abuse histories; young women also report great fear of future victimization. Findings also suggest that as a result of their decreased likelihood of using protection, women who reported any sexual or physical victimization are at increased risk for HIV and other STIs. Results support the critical need for targeted, comprehensive interventions that address substance abuse, sexual risk, and violence as interrelated phenomena.

Adult↗

Inhaled fluticasone in bronchiectasis: a 12 month study.

BACKGROUND: The clinical efficacy of inhaled corticosteroid (ICS) treatment has not been evaluated in bronchiectasis, despite the presence of chronic airway inflammation. METHODS: After three consecutive weekly visits, 86 patients were randomised to receive either fluticasone 500 mug twice daily (n = 43, 23F, mean (SD) age 57.7 (14.4) years) or matched placebo (n = 43, 34F, 59.2 (14.2) years) and reviewed regularly for 52 weeks in a double blind fashion. RESULTS: 35 and 38 patients in the fluticasone and placebo groups completed the study. Significantly more patients on ICS than on placebo showed improvement in 24 hour sputum volume (OR 2.5, 95% CI 1.1 to 6.0, p = 0.03) but not in exacerbation frequency, forced expiratory volume in 1 second, forced vital capacity, or sputum purulence score. Significantly more patients with Pseudomonas aeruginosa infection receiving fluticasone showed improvement in 24 hour sputum volume (OR 13.5, 95% CI 1.8 to 100.2, p = 0.03) and exacerbation frequency (OR 13.3, 95% CI 1.8 to 100.2, p = 0.01) than those given placebo. Logistic regression models revealed a significantly better response in sputum volume with fluticasone treatment than with placebo among subgroups of patients with 24 hour sputum volume <30 ml (p = 0.04), exacerbation frequency </=2/year (p = 0.04), and sputum purulence score >5 (p = 0.03). CONCLUSIONS: ICS treatment is beneficial to patients with bronchiectasis, particularly those with P. aerurginosa infection.

Administration, Inhalation↗

Biomechanical and electromyographic evaluation of ankle foot orthosis and dynamic ankle foot orthosis in spastic cerebral palsy.

This study evaluated the biomechanical and electromyographic effects of conventional ankle foot orthoses (AFOs) and dynamic ankle foot orthoses (DAFOs) on gait in patients with spastic cerebral palsy (CP). Thirteen patients with dynamic equinus underwent motion analysis with electromyography. Both AFOs and DAFOs provided longer stride length, permitted pre-positioning for initial contact, and successfully controlled the excessive plantarflexion during the swing phase. Median frequency (MF) of EMG signal indicated that extremely high firing was found in the patient's lower limbs compared to controls that resulted in tiredness. The DAFOs allowed a significantly larger total ankle range of motion than the AFOs. However, AFOs significantly reduced the MF while DAFOs did not. The reduced MF seen when wearing AFOs suggested an improvement of walking endurance. The DAFO had the advantage of less restriction on ankle movement, which avoids muscular atrophy and improves orthotic compliance.

Ankle Joint↗

In vitro study of regulation of IL-6 production in bronchiectasis.

Persistent airway inflammation is an important pathogenetic factor in bronchiectasis, and interleukin (IL)-6 is among the mediators implicated in regulation of inflammation in bronchiectatic airways. We postulated that airway secretion with its constituents of cytokines and enzymes would provide an environment for perpetuation of inflammation in vivo. We aimed to determine the action of sputum from patients with bronchiectasis on IL-6 production from cultured normal human bronchial epithelial (NHBE) cells and its modulation by anti-inflammatory drugs in vitro. Cultures of NHBE cells were tested with (i) sputum of bronchiectatic patients, (ii) anti-tumor necrosis factor-alpha (TNF-alpha) pre-treated sputum, or (iii) recombinant human (rh)-TNF-alpha. Alternatively, NHBE cells were incubated with one of the anti-inflammatory drugs before treatment with sputum or rh-TNF-alpha. IL-6 produced into the medium was assayed by ELISA. Sputum in bronchiectasis stimulated IL-6 production from NHBE cells by 1.9 times. This was largely attributable to TNF-alpha as pre-incubation of sputum sol with anti-TNF-alpha almost neutralized the sputum effect. Apart from dexamethasone, the other drugs exerted inhibitory effects on IL-6 production. Ibuprofen suppressed sputum-stimulated IL-6 production to levels above control and effect levelled off at 50-100 microg/mi, contrasting the dose-dependent suppression to control level with MK-663 (0.1-10 microg/ml) and to sub-control levels with triptolide (20-1000 ng/ml). Our results support that sputum in bronchiectasis can stimulate IL-6 production from NHBE cells, and TNF-alpha is an important cytokine mediating the process. The suppressive effects observed with ibuprofen, triptolide and MK-663 warrant further study.

Anti-Inflammatory Agents↗

Lymphoepithelioma-like carcinoma of the lung: experience with ten cases.

OBJECTIVE: Lymphoepithelioma-like carcinoma of the lung (LELC) is a rare form of non-small cell lung cancer predominantly affecting young non-smoking Asians, and there has been only limited experience in its palliative chemotherapy and radiotherapy. We investigated tumour response, time to progression and survival of LELC patients who received such treatment. DESIGN: We prospectively recruited patients with confirmed advanced LELC who were treated with chemoradiotherapy in our unit, a regional tertiary referral centre for lung cancer treatment. RESULTS: There were 10 patients (five males, age 47 +/- 9.8 years, median follow-up 22 months) with advanced LELC (respectively 1, 4, and 5 patients at TNM stage IIIA, IIIB and IV) who received systemic chemotherapy and radiotherapy. The primary chemotherapy regimen consisted of 5-fluorouracil/leucovorin/cisplatin. The response rates to 5-fluorouracil/leucovorin/cisplatin were 60% partial response, 10% stable disease, and 30% progressive disease. Eight patients were also given local radiotherapy. Five patients received salvage chemotherapy when disease progressed after primary chemotherapy. The overall median survival was 23.4 +/- 4.7 months. CONCLUSION: The encouraging response to combination chemotherapy with 5-fluorouracil/leucovorin/ cisplatin, although empirical, supports its use with radiotherapy in unresectable lymphoepithelioma-like carcinoma of the lung.

Adult↗

Lung cancer epidemiology and risk factors in Asia and Africa.

In industrialised countries, lung cancer is the most common form of cancer among males and it is growing among females. For both sexes, rates reflect smoking behaviours. The pattern appears to be different in Asia, particularly in China, where lung cancer rates in men reflect high smoking rates but high rates among non-smoking women appear to be related to other factors. The incidence of lung cancer is low in most African countries, but it is increasing. In addition to tobacco smoking, a number of etiological factors have been identified for lung cancer: indoor exposure to environmental tobacco smoke, cooking oil vapour, coal burning, or radon, outdoor air pollution and occupational exposure to asbestos and other carcinogens. Recent studies have shown that dietary factors may be important, with high consumption of vegetables and fruits being protective while preserved food and fatty food are harmful, and certain infections such as Mycobacterium tuberculosis, human papilloma virus and Microsporum canis are associated with a high risk of lung cancer. Among non-smokers, the probable role of genetic predisposition in lung cancer by increasing the individual's susceptibility to environmental carcinogens is currently being studied actively. As the single most important cause for lung cancer is tobacco smoke and, with increased sales, a major epidemic is predicted for both Asia and Africa, all health care professionals, government health authorities and national and international health organisations must join in a concerted effort against tobacco.

Africa↗

Pentaglobin in steroid-resistant severe acute respiratory syndrome.

SETTING: The treatment of severe acute respiratory syndrome (SARS) is at best controversial, although there is considerable anecdotal experience to show the benefits of corticosteroid therapy for selected patients. Some patients deteriorate relentlessly despite treatment with antibiotic, corticosteroid and mechanical ventilation. OBJECTIVE: To attempt to determine the clinical efficacy of pentaglobin, an IgM-enriched immunoglobulin preparation, on 12 severe SARS patients who continued to deteriorate despite corticosteroid and ribavirin therapy. DESIGN: Retrospective analysis of daily quantitative and radiographic data on the cohort in a regional teaching hospital. RESULTS AND CONCLUSION: There was significant improvement in radiographic scores, when compared with day 1, on days 5, 6 and 7 (P < 0.05) after commencement of pentaglobin treatment. Similarly, there was significant improvement in oxygen requirement, when compared with day 1, on days 6 and 7 (P < 0.05) after commencement of pentaglobin treatment. There were no reported adverse events attributable to pentaglobin administration. Ten patients made an uneventful recovery after treatment. One elderly man died from cardiorespiratory arrest despite clinical and radiological improvement, and another patient is making good progress. Pentaglobin is safe and probably effective in the treatment of steroid-resistant SARS. A double-blind placebo-controlled study should therefore be considered.

Adrenal Cortex Hormones↗

Exhaled nitric oxide in bronchiectasis: the effects of inhaled corticosteroid therapy.

SETTING: While exhaled nitric oxide (eNO) levels are reduced by inhaled corticosteroid therapy in asthma, such treatment effect is unclear in bronchiectasis. DESIGN: Stable non-smoking bronchiectasis patients were randomised to receive either fluticasone (1 mg/daily) or identical placebo via the Accuhaler device. RESULTS: Sixty non-smoking patients (38 women; mean age 56.4 +/- 12.7 years) were recruited. Of these, half received inhaled fluticasone and half placebo therapy. eNO was measured using a chemiluminescence analyser at 0, 4, 12, 24, 36 and 52 weeks. There was no significant difference in eNO levels between fluticasone and placebo patients over the study period. There was no correlation between baseline eNO with age, FEV1, FVC, 24 h sputum volume or number of bronchiectatic segments. Patients with Pseudomonas aeruginosa (PA) infection, but not their counterparts, displayed a correlation between 0- and 52-week eNO levels. PA infection was associated with significantly lower eNO levels among the patients. CONCLUSIONS: Inhaled fluticasone therapy, despite being an effective anti-inflammatory agent, has no significant effect on eNO production, either at individual time points or over the entire 52-week profile, in bronchiectasis. It appears that eNO might not reflect the extent of airway inflammation in bronchiectasis.

Administration, Inhalation↗

A multicenter phase II study of the efficacy and safety of docetaxel plus cisplatin in Asian chemonaïve patients with metastatic or locally advanced non-small cell lung cancer.

AIMS: To evaluate the efficacy and safety of docetaxel-cisplatin in patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). METHODS: Chemotherapy-naïve patients with histologically confirmed TNM stage III or IV NSCLC were recruited from 12 Asian trial centers. Patients received docetaxel (75 mg/m2) and cisplatin (75 mg/m2) every 3 weeks for 6 cycles. RESULTS: 130 of 146 patients were evaluable for efficacy (60% stage IV). Three complete and 58 partial responses were observed (overall response rate: 46.9%; 95% CI: 38.3-55.5%). Median time to progression was 6.9 months and median survival was 14.0 months; 1-year survival was 59.5%. Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 69.2%, 6.2% and 18.5% of patients, respectively. Grade 3/4 vomiting was observed in 13.7% and grade 3/4 neurosensory effects were observed in 2.7% of patients. There was one case of treatment-related death due to sepsis. CONCLUSION: Docetaxel-cisplatin is an effective and well-tolerated treatment in Asian patients with NSCLC.

Adult↗

Overview on SARS in Asia and the world.

Severe Acute Respiratory Syndrome (SARS) is the first major novel infectious disease to hit the international community in the 21st century. It originated in southern China in November 2002, reached Hong Kong in February 2003 and spread rapidly thereafter to 29 countries/regions on five continents. At the end of the epidemic, the global cumulative total was 8098 with 774 deaths. Seven Asian countries/regions were among the top ten on the list. Mainland China and Hong Kong, SAR, accounted for 87% of all cases and 84% of all deaths. Severe acute respiratory syndrome is caused by a novel coronavirus. It has alarmed the world with its infectivity and significant morbidity and mortality, its lack of a rapid, reliable diagnostic test and lack of effective specific treatment and vaccination. The adverse impact on travel and business around the world, particularly in Asia, has been enormous. Some lessons learnt from this epidemic included: (1) any outbreak of infectious disease can rapidly spread around the world by air travel; (2) early reporting of the outbreak to neighbouring countries/regions and the World Health Organization is essential to prevent international spread; and (3) infection control, tracing and quarantine of contacts are essential to control the epidemic. Many questions remain unanswered, including the origin and pathogenesis of the novel coronavirus, the natural history and the best specific treatment of the disease. The SARS-CoV has probably jumped from an animal host to humans. There is an urgent need to evaluate the human-animal habitat in southern China and to remove animal reservoirs if found.

China↗

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↗