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Stephenson I Nicholson KG 《BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy》1999,11(4):223-228
Influenza is an important epidemic and pandemic illness associated with serious morbidity and mortality in unprotected communities. Patients at increased risk of infection are those with pre-existing cardiopulmonary disease including asthma. The influenza virus has the ability to produce antigenic changes posing problems for vaccine development. Influenza vaccines have been available for over 50 years. Despite the continuing global threat posed by infection and recommendations in many countries that immunisation should be widely given, uptake rates are variable and often poor. It has been demonstrated that infection with influenza and other respiratory viral pathogens can produce exacerbations of asthma throughout the age groups. Despite this, vaccine uptake rates in asthmatic populations are quite low. Poor uptake rates are attributed to a number of factors and we review the evidence for the widely held view that influenza vaccination produces exacerbations of chronic airflow obstruction including asthma. Observational studies have found conflicting results: some post immunisation changes in bronchial hyperreactivity and increased requirements of bronchodilator therapy have been in some, but not all, studies. Placebo-controlled trials have not demonstrated any clinical deterioration although one study showed a small reduction in peak expiratory flow rate. Intranasal administration of cold-adapted live vaccines and new nucleic acid vaccines are briefly considered. Live adapted vaccines have been shown to be effective in influenza immunoprophylaxis and limited data on their use in patients with asthma suggest that they can be administered safely. In conclusion, based up on current studies and evidence, it seems likely that influenza infection produces morbidity in patients with asthma but that any potential adverse effects of influenza immunisation are outweighed by the benefits in this population. However, placebo-controlled trials are few and only small numbers of asthmatic patients have been investigated. 相似文献
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Clinical significance of respiratory bronchiolitis on open lung
biopsy and its relationship to smoking related interstitial lung
disease
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BACKGROUND: Respiratory bronchiolitis-associated interstitial lung disease (RBILD) is a rare form of interstitial lung disease which may present in similar fashion to other types of chronic interstitial pneumonia. The purpose of this study was to undertake a clinicopathological review of 10 patients with RBILD and to examine the clinical and imaging data related to its histopathological pattern, in particular the relationship of RBILD to smoking. METHODS: Thirteen out of 168 retrospectively reviewed patients, from whom biopsy specimens were taken for suspected diffuse lung disease, were identified with a histopathological pattern of RBILD. Three cases were rejected as follow up data were unavailable. The 10 remaining cases constituted the study group and both clinical and imaging data were collected from patients' notes and referring physicians. RESULTS: Histopathologically, four cases of RBILD overlapped with the pattern of desquamative interstitial pneumonitis (DIP) and nine also had microscopic evidence of centrilobular emphysema. Nine patients were smokers, ranging from 3 to 80 pack years. The one non-smoker had an occupational exposure to the fumes of solder flux. The sex distribution was equal with an age range of 32-65 years. Two patients were clubbed. Lung function tests showed both restrictive and obstructive patterns together with severe reductions in carbon monoxide transfer factor in seven patients. Chest radiographs showed reticular or reticulonodular infiltrates in five patients and a ground glass pattern in two. CT scans were consistent with either DIP or RBILD in six of eight patients. Although seven patients remained stable or improved, either with or without treatment, three patients deteriorated. CONCLUSIONS: This study adds weight to the hypothesis that smoking can cause clinically significant interstitial lung disease, with deterioration in pulmonary function despite treatment. Given the overlapping histopathological patterns of RBILD and DIP and their strong association with smoking, the term "smoking related interstitial lung disease" is suggested for those patients who are smokers. 相似文献
87.
1. 12,14-dichlorodehydroabietic acid (12,14-Cl2DHA) reduced GABA-stimulated uptake of 36Cl- into mouse brain synaptoneurosomes suggesting inhibition of mammalian GABA(A) receptor function. 2. 12,14-Cl2DHA did not affect the binding of [3H]-muscimol to brain membranes but displaced specifically bound [3H]-EBOB. The inhibitory effect on [3H]-EBOB binding was not reversible. 12,14-Cl2DHA reduced the availability of [3H]-EBOB binding sites (Bmax) without changing the KD of the radioligand for remaining sites. 12,14-Cl2DHA did not affect the rate of association of [3H]-EBOB with its chloride channel receptor, but increased the initial rate of [3H]-EBOB dissociation. 3. 12,14-Cl2DHA enhanced the incidence of EPSCs when rapidly applied to cultured rat cortical neurones. Longer exposures produced block of IPSCs with marked increases in the frequency of EPSCs and min EPSCs. 12,14-Cl2DHA also irreversibly suppressed chloride currents evoked by pulses of exogenous GABA in these cells. 4. Ultimately, 12,14-Cl2DHA inhibited all synaptic traffic and action currents in current clamped cells indicating that, in contrast to picrotoxinin (which causes paroxysmal bursting), it is not fully selective for the GABA(A) receptor-chloride channel complex. 5. The depolarizing block seen with 12,14-Cl2DHA in amphotericin-perforated preparations implicates loss of Ca2+ buffering in the polarity change and this may account for inhibition of spontaneous action potentials. 6. Our investigation demonstrates that 12,14-Cl2DHA blocks GABA-dependent chloride entry in mammalian brain and operates as a non-competitive insurmountable GABA(A) antagonist. The mechanism likely involves either irreversible binding of 12,14-Cl2DHA to the trioxabicyclooctane recognition site or a site that is allosterically coupled to it. We cannot exclude, however, the possibility that 12,14-Cl2DHA causes localized proteolysis or more extensive conformational change within a critical subunit of the chloride channel. 相似文献
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Scarfe GB Wright B Clayton E Taylor S Wilson ID Lindon JC Nicholson JK 《Xenobiotica; the fate of foreign compounds in biological systems》1999,29(1):77-91
1. The metabolism and urinary excretion of 2-chloro-4-trifluoromethylaniline has been studied in the rat using 19F-NMR spectroscopy and directly coupled HPLC-NMR-MS methods. The compound was dosed to three male Sprague-Dawley rats (50 mg kg(-1) i.p.) and urine collected over 0-8, 8-24 and 24-48 h post-dosing. 2. A total urinary recovery of 56.3+/-2.2% of the dose was achieved up to 48 h after dosing. The major metabolite in the urine was identified as 2-amino-3-chloro-5-trifluoromethylphenylsulphate accounting for a total of 33.5+/-2.2% of the dose. 3. Further metabolites detected and characterized included 2-chloro-4-trifluoromethylphenylhydroxylamine glucuronide (13.2+/-0.5% of the dose), 2-amino-3-chloro-5-trifluoromethylphenylglucuronide (3.8+/-0.4% of the dose) and 2-chloro-4-trifluoromethylaniline-N-glucuronide (3.6+/-0.1% of the dose). Several minor metabolites were also found and identified, including 2-chloro-4-trifluoromethylphenylsulphamate, which together accounted for 2.1+/-0.4% of the dose. 4. Directly coupled HPLC-NMR-MS and 19F-NMR spectroscopy is shown to provide an efficient approach for the unequivocal and rapid determination of the quantitative urinary metabolic fate and excretion balance of a fluorinated xenobiotic without the necessity for specific radiolabelling. 相似文献
90.
'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data 总被引:109,自引:0,他引:109
Nicholson JK Lindon JC Holmes E 《Xenobiotica; the fate of foreign compounds in biological systems》1999,29(11):1181-1189