Detection and characterisation of extended-spectrum beta-lactamases among blood stream isolates of Enterobacter species in Hong Kong.

1. Extended-spectrum beta-lactamase(ESBL) resistance in Enterobacter spp may be under-recognised. 2. Detection methods for ESBL resistance in Enterobacter spp may need to be modified.

Increased adrenomedullin expression in lungs in endotoxaemia.

Adrenomedullin (AM) is a peptide involved in cardiovascular homeostasis and in inflammation. We examined its expression in a rat model of endotoxaemia. Male Sprague-Dawley rats received intraperitoneal injection of 5 or 10 mg/kg lipopolysaccharide (LPS), or saline as control. Rats were killed at 1, 3, 6, 12 and 24 h after injection. LPS at 5 mg/kg, but not saline, increased plasma AM significantly at 3 h. At 10 mg/kg, plasma AM was raised at 3, 6 and 12 h. Immunoreactive AM concentration in lung increased after 5 or 10 mg/kg LPS, but not saline. PreproAM mRNA level in lung was significantly increased at 3 and 6 h. In conclusion, endotoxin stimulates the expression of AM in the lungs and increases its circulatory concentration. AM may be involved in the systemic response to sepsis.

Risk factors associated with lung cancer in Hong Kong.

The purpose of this study was to investigate the risk factors associated with lung cancer in Hong Kong. Three hundred and thirty-one histologically or cytologically proven consecutive cases of lung cancer and the same number of in- and out-patients without cancer matched for age and sex were recruited for this study using a detailed questionnaire completed by a trained interviewer. Smoking was the most important risk factor associated with lung cancer but the attributable risk (AR) was estimated to be 45.8% in men and 6.2% in women, considerably lower compared with those estimated in early 1980s. In addition, among women, exposure to environmental tobacco smoke (ETS) at work+/-at home and lack of education, were independent risk factors for lung cancer with adjusted odds ratio (OR) 3.60, (95% confidence interval (CI) 1.52-8.51) and OR 2.41 (95% CI 1.27-4.55), respectively. Among men, exposure to insecticide/pesticide/herbicide, ETS exposure at work or at home, and a family history of lung cancer and were independent risk factors with adjusted OR 3.29 (95% CI 1.22-8.9, OR 2.43, 95% CI 1.24-4.76 and OR 2.37, 95% CI 1.43-3.94, respectively). Exposure to incense burning and frying pan fumes were not significant risk factors in both sexes. A moderate or high consumption of fat in the diet was associated with increased risk in men but decreased risk in women. The results of this study suggested that as the prevalence of smoking declined, the influence of smoking as a risk factor for lung cancer decreased even further. Moreover, the contribution of other environmental, occupational and socioeconomic factors may be more apparent as etiological factors for lung cancer in a population with relatively high lung cancer incidence but low AR from active smoking.

The relationship between mediastinal lymph node attenuation with parenchymal lung parameters in silicosis.

OBJECTIVE: Attenuation changes on computed tomography (CT) in mediastinal lymph nodes (LN) may be related to lung alterations and functional impairment in silicosis. DESIGN: CT and clinical data of 41 (64.2 +/- 8.3 years) males with silicosis were retrieved. Attenuation type (calcified, hyperdense, normodense) and calcification pattern (central, eccentric, dense, eggshell, speckled) of mediastinal LN were evaluated; LN attenuation of uncalcified LNs quantified on CT in six LN stations. Nodular profusion (CT-NP) and progressive massive fibrosis (CT-PMF) were graded. Relationships between LN, CT, lung function and clinical parameters were determined. RESULTS: LN sites were paratracheal (n = 39), subcarinal (n = 39), tracheobronchial (n = 37), aortopulmonary (n = 37), hilar (n = 27), and peri-oesophageal (n = 21). LNs were calcified, hyperdense and normodense in 107, 85 and 54 LN stations, respectively. Uniformly calcified LN was most common, followed by speckled calcification. Central, eccentric and eggshell calcification was rare. CT-NP scores > or = 16 were associated with higher LN attenuation and number of calcified LN stations than CT-NP scores < 16. PMF had no influence over LN morphology or calcification pattern. LN attenuation correlated with CT-PMF (r = 0.36, P = 0.01), CT-NP (r = 0.54, P < 0.001) and DLCO/VA (r = -0.33, P = 0.02). CONCLUSION: Uniformly calcified and hyperdense LNs are common in silicosis, and eggshell LN calcification is rare. There are associations between LN attenuation and lung function impairment, and CT grades of nodular profusion and PMF.

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.

Normal 24-hour ambulatory proximal and distal gastroesophageal reflux parameters in Chinese.

OBJECTIVE: To quantify normal proximal and distal oesophageal acid parameters in healthy Chinese. DESIGN: Observational study. SETTING: University teaching hospital, Hong Kong. SUBJECTS AND METHODS: Twenty healthy adults who were not on medication and were free from gastrointestinal symptoms were recruited by advertisement. Ambulatory oesophageal acid (pH<4) exposure parameters were recorded at distal and proximal sites, 5 and 20 cm, respectively above the lower oesophageal sphincter. RESULTS: The 95th percentile for reflux parameters assessed in the distal/proximal oesophagus were: percent total time pH<4, 4.6/0.7%; percent upright time pH<4, 7.0/1.1%; percent supine time pH<4, 4.5/0.5%; number of reflux episodes, 73/12; number of reflux episodes with pH<4 for >5 minutes, 4/0; and the longest single acid exposure episode, 11.2/3.0 minutes. CONCLUSION: Physiological gastroesophageal reflux occurs in healthy Chinese. These initial data provide a preliminary reference range that could be utilised by laboratories studying Chinese subjects.

Clinical outcomes of bacteremic pneumococcal infections in an area with high resistance.

In a retrospective study designed to gather information in a region with high antimicrobial resistance, the outcomes of 216 episodes of laboratory-confirmed pneumococcal bacteremia treated in Hong Kong between 1995 and 2001 were assessed. The patients had a mean age (+/-standard deviation) of 40+/-33.7 years. In all patients, the clinical diagnosis was confirmed by isolation of Streptococcus pneumoniae from blood (n=216), cerebrospinal fluid (n=7) and/or other sterile sites (n=12). Penicillin nonsusceptibility was found in 37.5% of the isolates (20.8% intermediate and 16.7% resistant). Penicillin nonsusceptibility was not a risk factor for inpatient mortality (p=0.7), nor did it affect duration of fever (p=0.4), requirement for intensive care unit admission (p=0.4) or development of suppurative complications (p=0.2). Advanced age (OR 11.3, 95%CI 4.5-28.2, p<0.01), critical illness (OR 11.3, 95%CI 4.5-28.2, p<0.001) and discordant therapy (OR 4.3, 95%CI 1.7-10.9, p<0.002) involving agents with poor anti-pneumococcal activity (but not penicillins and broad-spectrum beta-lactam agents) were significantly associated with mortality.

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.

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.

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.

Prolonged disturbances of in vitro cytokine production in patients with severe acute respiratory syndrome (SARS) treated with ribavirin and steroids.

Severe acute respiratory syndrome (SARS) is a new disease which has spread rapidly and widely. We wished to know whether evaluation of in vitro cytokine production could contribute to improved understanding of disease pathogenesis and to better patient management. Numbers of unstimulated and mitogen-stimulated cytokine-secreting peripheral blood mononuclear cells were measured repeatedly during and after hospitalization in 13 patients with SARS using enzyme-linked immunospot technology. Numbers of interferon-gamma, interleukin (IL)-2, IL-4, IL-10 and IL-12 secreting cells induced by T cell activators were below normal in many or most patients before and during treatment with corticosteroids and ribavirin but returned essentially to normal after completion of treatment. Staphylococcus aureus Cowan 1 (SAC)-stimulated IL-10 secreting cells were increased in early SARS but fell during treatment. SAC-induced IL-12 secreting cells were deficient before, during and long after treatment. Numbers of cells induced to produce IL-6 and tumour necrosis factor-alpha by T cell or monocyte activators were higher than normal in many early SARS patients and were still increased in some during and after treatment. We conclude that prolonged dysregulated cytokine production occurs in SARS and that future studies should be directed at improving anti-inflammatory and antiviral therapies in order to limit cytokine impairment.

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.