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A simple and specific LC-DAD-ESI-MS/MS method has been developed and applied for the primary investigation of the chemical constituents absorbed or metabolized in vivo, after the rat oral administration of Erxian Decoction (EXD), a Chinese medicine prescription for menopausal syndromes. Through the online ESI-MS(n) analysis, a total of 35 compounds have been identified or tentatively characterized from the seven tested samples, and 13 of them were unambiguously identified through a direct comparison of the retention time, UV spectra and MS(n) fragmentation patterns with the authentic ones. The results showed that 21 compounds were detected from rat plasma, 20 compounds were detected from rat kidneys and adrenal glands, 19 compounds were detected from rat ovaries, 12 compounds were found in rat intestines, nine compounds were identified from rat livers and nine compounds were detected from rat brains at certain time points after oral administration of the effective EXD fraction.

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ETHNOPHARMACOLOGICAL RELEVANCE: Many clinical and experimental reports demonstrated that Erxian Decoction (EXD) was effective in relieving menopausal syndrome. AIM OF THE STUDY: The mechanisms of action of EXD were explored on the endocrine and antioxidant regimen. MATERIALS AND METHODS: Menopause causes a decline in both endocrine function and activities of antioxidant enzymes. In this study, 12-month-old female Sprague-Dawley-rats (SD-rats) with a low serum estradiol level were employed. Their endocrine functions after treatment with EXD were assessed by the determination of their serum estradiol level and ovarian mRNA levels of aromatase, which is a key enzyme for biosynthesis of estradiol. Meanwhile, superoxide dismutase-1 (SOD), catalase (CAT) and glutathione peroxidase (GPx-1) in the liver were also determined to assess the effect of EXD on the antioxidant regimen. RESULTS: Results revealed a significant elevation in serum estradiol level and the mRNA level of ovarian aromatase and liver CAT in the EXD-treated menopausal rat model. CONCLUSIONS: The results obtained from mRNA and estradiol level of the present investigation revealed that the EXD relieves the menopausal syndrome involved an increase of endocrine and antioxidant function through, at least, the activation of aromatase and CAT detoxifying pathways.

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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.

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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.

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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.

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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.

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A prospective study was undertaken to identify clinical, radiographical, haematological and biochemical profiles of severe acute respiratory syndrome (SARS) patients. A prediction rule, which demarcates low from high risk patients for SARS in an outbreak situation was developed. A total of 295 patients with unexplained respiratory illnesses, admitted to Queen Mary Hospital, Hong Kong SAR, China, in March to July 2003, were evaluated for clinical, radiological, haematological and alanine transaminase (ALT) data daily for 3 days after hospitalisation. In total, 44 cases were subsequently confirmed to have SARS by RT-PCR (68.2%) and serology (100%). The scoring system of attributing 11, 10, 3, 3 and 3 points to the presence of independent risk factors, namely: epidemiological link, radiographical deterioration, myalgia, lymphopenia and elevated ALT respectively, generated high and low-risk (total score 11-30 and 0-10, respectively) groups for SARS. The sensitivity and specificity of this prediction rule in positively identifying a SARS patient were 97.7 and 81.3%, respectively. The positive and negative predictive values were 47.8 and 99.5%, respectively. The prediction rule appears to be helpful in assessing suspected patients with severe acute respiratory syndrome at the bedside, and should be further validated in other severe acute respiratory syndrome cohorts.

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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 5 (p = 0.03). CONCLUSIONS: ICS treatment is beneficial to patients with bronchiectasis, particularly those with P. aerurginosa infection.

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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.

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In 2003, the onset of severe acute respiratory syndrome (SARS) caused worldwide chaos. Although SARS was eradicated by isolation towards the end of 2003, sporadic cases have been reported in Singapore, Taiwan and mainland China. In this review, SARS is discussed as a disease, as well as its diagnosis, management and pharmacotherapy. Respiratory physicians and healthcare professionals have to be aware of advances in the understanding of the diagnosis and management of severe acute respiratory syndrome. More research is required in order to prepare for if this respiratory infection recurs, but there are concerns that adequate pharmaceutical support may be lacking for the development of a vaccine.

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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.

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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.

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Bronchiectasis is a common disease in the developing world. While the aetiology of bronchiectasis is diverse, many patients suffer from idiopathic disease. Although the pathogenesis of bronchiectasis is poorly understood, there are three distinct pathogenic elements, namely infection, inflammation and enzymatic actions. These interact to perpetuate airway destruction in many cases. There are four patient stereotypes: rapidly progressive, slowly progressive, indolent disease and haemoptysis-predominant. The diagnosis of bronchiectasis is best made with high resolution computed tomography, which should be followed by delineation of aetiology and evaluation of disease severity. Management of bronchiectasis is unsatisfactory and there are no disease-modifying drugs or treatment guidelines. Specific therapy to correct an underlying defect should be instituted whenever possible, although established disease often continues to deteriorate relentlessly. Treatment with prolonged, high-dose antibiotics is useful for exacerbations and probably also for some severely affected patients with frequent exacerbations who habour Pseudomonas aeruginosa in their airways. Commencement of long-term nebulised aminoglycoside, elective in-patient intravenous antibiotic therapy, long-term oral antibiotic or low-dose macrolide therapy requires special considerations. Inhaled corticosteroid therapy reduces chemokine expression in bronchiectasis in vivo, and may be useful for some patients. For severely affected patients, the use of non-invasive positive-pressure ventilation with supplementary oxygen sometimes helps. The lack of enthusiasm about bronchiectasis has already resulted in a lack of research in the treatment of this frustrating disease, and such research needs to be encouraged.

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This review examines whether the comprehensive programme recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), developed mostly by physicians in industrialised countries, can be applied in developing countries. In developing countries, there are several major limitations to the implementation of the programme. First, management of chronic obstructive pulmonary disease (COPD) patients is not a priority in competing for health care resources. Second, only major medical centres in developing countries have spirometers; the reliance on spirometric testing for diagnosis, staging and treatment options, as recommended by the GOLD guidelines, makes it almost impossible for the programme to be implemented. Third, in many Asian and African countries, regular monitoring is often restricted to patients with severe COPD who have frequent hospitalisations or clinic visits for exacerbations and complications. Fourth, the choice of therapy usually depends on the availability and cost of drugs. Finally, given the aetiological role of sequelae of lung infections, including tuberculosis, the appropriateness and safety of using intermittent courses of oral steroids during acute exacerbations and of long-term, high-dose inhaled corticosteroids for moderate to severe COPD in developing countries has not been evaluated. Developing countries in Asia and Africa may need to adapt the GOLD guidelines according to varying aetiology, local health care resources, socio-economic and cultural factors and development of health services. Prevention programmes, especially for tobacco control, are of paramount importance. National and international efforts must be directed towards controlling the tobacco epidemic in developing countries to reduce the burden of COPD and other tobacco-induced diseases.

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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.

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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.

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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.

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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.

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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.

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