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At least 469 records · Page 26Linked to original sources
PubMed2006

Chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is thought to have a worldwide prevalence of 0.4-1% with approximately 240,000 patients in the UK. Diagnosis is based on clinical criteria and critically depends on exclusion of other physical and psychiatric diseases. Studies of pathogenesis have revealed immune system abnormalities and chronic immune activation, dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, brain abnormalities, evidence of emotional stress (comprising host aspects) and evidence of exogenous insults, for example, various microbial infections (Epstein-Barr virus, enteroviruses, parvovirus B19, Coxiella burnetii and Chlamydia pneumoniae), vaccinations and exposure to organophosphate chemicals and other toxins (comprising environmental aspects). Emotional stress appears to be very important as it reduces the ability of the immune system to clear infections, it's presence has been shown to determine whether or not an individual develops symptoms upon virus infection, and it leads to activation of the HPA axis. But, emotional stress is distinct from depression, the presence of which precludes a diagnosis of CFS. There is no specific treatment for CFS other than the much underutilised approach of specific treatment of virus infections. Current priorities are to understand the molecular pathogenesis of disease in terms of human and virus gene expression, to develop a diagnostic test based on protein biomarkers, and to develop specific curative treatments.

Diagnosis, Differential↗
PubMed2004

Exhaled breath condensate (EBC) collection in cats--description of a non-invasive technique to investigate airway disease.

Exhaled breath condensate has been collected in other species and used as a non-invasive method of evaluating airway disease by measurement of various markers in the fluid, including hydrogen peroxide, nitric oxide, leukotrienes and prostaglandins. We describe a novel technique for the collection of exhaled breath condensate from cats, which enabled collection of fluid and measurement of its hydrogen peroxide concentration. Further studies will be needed to establish the value of this technique in the investigation of feline respiratory disease.

Animals↗
PubMed2026

Association of lipoprotein-associated phospholipase A2 with recurrence risk and its predictive value in large artery atherosclerotic stroke.

OBJECTIVE: To investigate the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) with large artery atherosclerotic (LAA) stroke and its predictive value for recurrence. METHODS: We consecutively enrolled 412 acute LAA stroke patients. Using a cutoff of 200&#xa0;ng/mL, patients were divided into high and low Lp-PLA2 groups, and into recurrence and non&#x2011;recurrence groups based on 1&#x2011;year follow&#x2011;up. Baseline characteristics, lipid profiles, National Institutes of Health Stroke Scale (NIHSS) scores, and vascular stenosis degree were compared. Binary logistic regression and Receiver Operating Characteristic (ROC) analysis were used to identify independent risk factors and evaluate predictive value. RESULTS: The high Lp-PLA2 group had significantly higher low-density lipoprotein cholesterol (LDL-C), small dense low-density lipoprotein cholesterol (sdLDL-C), prevalence of severe stenosis (&#x2265;70%), and proportion of NIHSS&#xa0;>&#xa0;15 (all P&#xa0;<&#xa0;0.05). The recurrence group showed elevated Lp-PLA2, higher LDL&#x2011;C and sdLDL-C, more severe neurological deficits, and more severe stenosis (all P&#xa0;<&#xa0;0.001). Multivariable regression identified elevated Lp-PLA2 (per 10&#xa0;ng/mL: OR&#xa0;=&#xa0;1.139, 95% CI: 1.089-1.191), moderate (OR&#xa0;=&#xa0;3.145) and severe (OR&#xa0;=&#xa0;11.663) neurological deficits, and severe stenosis (OR&#xa0;=&#xa0;9.390) as independent risk factors for recurrence (all P&#xa0;<&#xa0;0.05). The Area Under the Curve (AUC) of Lp-PLA2 was 0.75 (95% CI: 0.69-0.82), with an optimal cutoff of 208.95&#xa0;ng/mL. CONCLUSION: Elevated Lp-PLA2 is associated with adverse lipid profiles, more severe neurological deficits, and greater vascular stenosis in LAA stroke patients, and independently predicts 1&#x2011;year recurrence. Lp-PLA2 shows moderate predictive value, supporting its potential for risk stratification.

Humans↗
PubMed2006

Exhaled NO and breath condensate.

A growing interest has recently directed toward non invasive methods, such as exhaled nitric oxide (FE(NO)) measurement and exhaled breath condensate (EBC) collection, for the assessment of asthmatic inflammation. FE(NO) is a reliable marker of eosinophilic airway inflammation and it can be measured by means of a standardized technique in children starting from the age of 4. FE(NO) may have useful applications both in asthma diagnosis and monitoring. EBC is obtained cooling exhaled air and its composition is believed to mirror the characteristics of airway lining fluid. The compounds detected in EBC are markers of inflammation and oxidative stress occurring in asthmatic lung. While EBC is still only a research tool, FENO measurement is closer to clinical practice and lately it has been included in some treatment algorithms for asthma.

Asthma↗
PubMed2003

High levels of interleukin-6 in the exhaled breath condensate of patients with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the respiratory tract. METHODS: We investigated the presence of interleukin-6 (IL-6: a cytokine secreted by monocytes/macrophages, T cells, B cells, fibroblasts, bone marrow stromal cells, keratinocytes and endothelial cells) in the exhaled breath condensate of 16 exsmokers with moderate COPD, 12 healthy non-smokers. IL-6 was measured by means of a specific enzyme immunoassay. RESULTS: IL-6 levels were detectable in all of the subjects, but were higher in the COPD patients (8.0 +/- 0.1 pg/ml; P < 0.0001) than in the healthy non-smokers (4.9 +/- 0.2 pg/ml) with a correlation in this group between age and IL-6 levels (r = 0.597; P < 0.05). CONCLUSIONS: The increased IL-6 levels in exhaled breath condensate may reflect airway inflammation in patients with COPD.

Adult↗
PubMed2004

Elevated exhalation of hydrogen peroxide and thiobarbituric acid reactive substances in patients with community acquired pneumonia.

BACKGROUND: Bacterial pneumonia involves influx of activated phagocytes into distal airways. These cells release oxidants including H2O2, that may be exhaled or induce peroxidative damage to lung tissues with formation of thiobarbituric reactive substances (TBARs). STUDY OBJECTIVES: To determine whether concentrations of H2O2 and TBARs in exhaled breath condensate (EBC) is elevated and correlate with systemic response to pneumonia during 10 days of hospital treatment. DESIGN: The concentration of H2O2 and TBARs was measured in EBC of 43 inpatients with community acquired pneumonia (CAP) and 20 healthy never smoked subjects over 10 days and were accompanied by monitoring of WBC count, serum concentration of C-reactive protein (CRP) and peroxyl radical-trapping capacity. RESULTS: Patients with CAP exhaled 4.6-, 3.7-, 3.9-, 3.3-times more H2O2 than healthy controls at 1st, 3rd, 5th and 10th day of treatment (P<0.05), respectively. EBC concentrations of TBARs were elevated at 1st and 3rd day. H2O2 and TBARs levels decreased along with treatment course. Correlation (P<0.05) was found between H2O2 levels and CRP and WBC count (r = 0.31) at 1st day and between TBARs and CRP at 5th (r = 0.34) and 10th day (r = 0.46). The mean H2O2 exhalation estimated over ten days of treatment correlated with pneumonic chest X-ray score (r = 0.42), CRP levels (r = 0.46) and WBC count (r = 0.33) at admission (P<0.05). CONCLUSIONS: Pneumonia is accompanied by oxidative stress in airways that moderately correlates with intensity of systemic inflammatory response. Determination of H2O2 in EBC may be helpful for non-invasive monitoring of oxidants production during lower respiratory tract infection.

Adult↗
PubMed2004

Adenosine 5'-monophosphate increases levels of leukotrienes in breath condensate in asthma.

Hyperresponsiveness (AHR) is a key physiological abnormality in asthma. In clinical and research studies AHR is measured bronchial challenge, with methacholine (MCh), but more recently with adenosine-5'-monophosphate (AMP). In the search for markers of airway inflammation in asthmatic patients, we measured the concentrations of histamine and cysteinyl-leukotrienes (cys-LTs) before and after MCh and AMP challenges in the exhaled breath condensate of 13 patients with mild asthma (FEV1 78.5%pred) and nine healthy non-smokers, using specific enzyme immunoassays. With methacholine challenge we did not find any differences between asthmatics and normal subjects in the pre- and post-challenge concentrations of cys-LTs: 27.2+/-1.4 vs. 29.2+/-1.2 pg/ml and 26.3+/-2.2 vs. 27.5+/-4.2 pg/ml, respectively or histamine: 5.1+/-0.4 vs. 5.1+/-0.6 nM and 4.5+/-0.4 vs. 4.4+/-0.3 nM; P>0.05). In asthmatic patients cys-LT levels were significantly higher after AMP challenge (56.2+/-9.7 vs. 31.7+/-6.9 pg/ml; P<0.05); but there was no difference in healthy subjects (27.2+/-4.6 vs. 30.3+/-4.7 pg/ml). There was no difference in histamine concentrations in asthmatic (5.9+/-1.8 vs. 4.5+/-0.5 nM), or healthy subjects (5.5+/-0.4 vs.5.7+/-0.9 nM) after AMP challenge. In conclusion, our results show that the cys-LTs are increased in exhaled breath condensate after AMP challenge, which may indicate that the AMP acts indirectly by releasing cys-LTs from primed mast cells. The detection of LTs and histamine in exhaled breath condensate may be useful in monitoring asthma.

Adenosine Monophosphate↗
PubMed2005

Repeatability of standardised nasal nitric oxide measurements in healthy and asthmatic adults and children.

UNLABELLED: Several nasal nitric oxide (NO) measurement techniques have been described, but there is not a widespread measurement technique for measurement of nasal NO. In this study we evaluated the repeatability of one technique of nasal NO measurements using the nasal application of the NIOX system. METHODS: Three nasal NO measurements (NIOX Nitric Oxide Monitoring System, Aerocrine, Sweden) were made on a single occasion in 22 healthy subjects and 27 patients with asthma, aged 5-69 years. Nasal NO was sampled during breath hold from one nostril at a flow rate of 5 ml/s. RESULTS: The repeatability of nasal NO assessed by the coefficient of variation (CV) was 12.5% (95% Confidence interval (CI) 11.0-14.7%) for the total population. Healthy adults had a significantly better repeatability than healthy children (P<0.008). The mean NO level for the total population was 837 ppb. The mean NO levels in children were lower than in the adults (751 and 897 ppb, respectively). The mean breath hold length needed to obtain a steady NO plateau for all subject categories combined was 20.4+/-6.01 s. The average number of attempts needed to obtain three approved NO measurements was 5.4 (range 3-13) for the total population. There were no significant differences between the different subject categories. When using two measurements per session instead of three, the overall CV was 10.5% (95% CI 8.8-13.1%). Most subjects found the measurements easy to perform and all of them would accept to do the examination as a routine. CONCLUSIONS: Nasal NO measurements in NIOX may provide a useful reliable clinical tool to assess and monitor upper airways in different diseases, for example PCD and rhinitis, and are acceptable by both healthy and asthmatic adults and children, as a part of their routine visit to a physician.

Adolescent↗
PubMed2005

Exhaled carbon monoxide levels in atopic asthma: a longitudinal study.

Exhaled carbon monoxide (eCO) is a potential non-invasive marker of airway inflammation. We have investigated the cross-sectional and longitudinal relationship between eCO and lung function and bronchial reactivity in 69 adults with atopic asthma, in the course of participation in a 6-week randomised placebo-controlled trial of vitamin E supplementation. At baseline, there was no cross-sectional association between absolute eCO levels and either forced expiratory volume (FEV(1)), forced vital capacity (FVC) or bronchial reactivity. However, in the longitudinal analysis within the placebo group, a rise in mean eCO was significantly associated with improvement in bronchial reactivity (change in eCO (parts per million) per natural log unit change in bronchial hyperreactivity 0.498, 95% confidence interval 0.071 to 0.924, P=0.024). These findings suggest that, contrary to previous data, there is no cross-sectional relationship between eCO and lung function or bronchial reactivity, but that there may be a longitudinal trend with bronchial reactivity that is worth further investigation.

Adolescent↗
PubMed2006

Variability of nitric oxide metabolites in exhaled breath condensate.

The collection of exhaled breath condensate (EBC) is simple and non-invasive, however, there are few data on the methodological aspects affecting concentrations of compounds in EBC. The aim of this study was to investigate methodological issues for measuring nitric oxide metabolites (NO(x)) in EBC. Twenty-five healthy adults (12 females, age range 23-55 years) and 22 children (11 females, age range 7-6 years) were recruited for studies investigating inter- and intra-day repeatability, repeatability with controlled expiratory flows and temperature, flow dependence, and analytical variability of EBC NO(x). Both intra- and inter-day repeatability was poor with a coefficient of repeatability of 103.4% of the mean difference between intra-day (15 min) measures and 118.6% of inter-day (24 h) differences. Repeatability was not improved when expiratory flow and temperature of the collection device were controlled. However, some of the variability (approximately 50%) may be accounted for by variability in the analytical technique (analytical variability) and this may result from difficulties in controlling for contamination. NO(x) levels were not affected by different expiratory flows in either adults or children but there was still significant variation within individuals. Levels of NO(x) in EBC seem to be highly variable and this needs to be considered if EBC NO(x) is to be used in clinical studies.

Adult↗
PubMed2005

Exhaled breath condensate levels of 8-isoprostane, growth related oncogene alpha and monocyte chemoattractant protein-1 in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) patients have increased neutrophils and macrophages in their lungs, and inflammation of the airway is related to oxidative stress. This study assessed the levels of 8-isoprostane (an oxidative stress marker) and chemokines related to neutrophil and monocyte inflammation (growth-related oncogene alpha [GROalpha] and monocyte chemoattractant protein-1 [MCP-1]) in the airway of ex-smoking COPD patients by exhaled breath condensate (EBC) collection. Thirty-two (28 males) stable COPD patients (14 with FEV(1) 50% [Group 1], 18 with FEV(1) <50% predicted [Group 2]) and 18 non-smoking age and sex-matched controls were studied in this cross-sectional study. EBC was collected using the EcoScreen (Jaeger, Germany) during 10 min of tidal breathing with the nose clipped. Concentrations of 8-isoprostane, GROalpha and MCP-1 were measured by enzyme immunoassays. COPD patients had a higher concentration of 8-isoprostane than controls (COPD versus control, P<0.001; Group 1 versus Group 2, P=0.045). 8-isoprostane increased across the groups from normal, Group 1 to Group 2 (r=0.64, P<0.001). The median intraquartile range (IQR) levels in pg/ml for GROalpha were 45.3(44.5-46.5), 45.4(44.5-46.0), 46.0(45.6-47.3), whereas MCP-1 levels were 5.3(5.2-5.9), 6.2(5.4-6.9) and 5.7(5.5-6.4) in Group 1, Group 2 COPD and control subjects, respectively. GROalpha level was lower in COPD patients when compared to controls (P=0.01). MCP-1 level did not differ between COPD and the control group. 8-isoprostane level, but not GROalpha and MCP-1, in EBC was increased in COPD patients with poorer lung function. This suggests an increased oxidative stress in the airway in patients with more severe COPD.

Aged↗
PubMed2005

Crop-specific human exposure assessment for polycyclic aromatic hydrocarbons in Czech soils.

Polycyclic aromatic hydrocarbons (PAH) are pollutants frequently found in soils, particularly in urban areas. From polluted soils, the PAH can be taken up into crops and the consumption of these crops can result in a human health risk. We estimated the bioconcentration factors (BCF) in the edible plant tissues for PAH using crop-specific models for leafy vegetables, root vegetables, potatoes and tree fruits. The estimates were compared with results from the empirical regression of Travis and Arms (T&A) for above-ground vegetation. The comparison shows that the use of crop-specific models resulted in lower BCF values of pollutant concentrations in fruits, potatoes and leafy vegetables, particularly for the heavier PAH (M>220 g mol(-1)). However, the crop-specific models yielded higher BCF values for root vegetables (carrot) and leafy vegetables if the attached soil particles (1%) were considered. Consequently, the average daily intake of benzo(a)pyrene (BaP) by an adult Czech through fruits and vegetables was estimated with the crop-specific models to be 190 ng BaP per person, and 460 ng BaP per person with the T&A regression, for a soil concentration of 1 mg BaP kg(-1) soil (wet wt.). A virtually safe oral dose of BaP, as a marker of the carcinogenic PAH, was suggested by a European expert commission to be below 4.2 to 35 ng per person and day. Using these figures, an acceptable soil concentration of BaP was estimated for the purpose of crop production to be below 0.02 or 0.18 mg kg(-1) (wet wt.) with the crop-specific models, and below 0.01 or 0.08 mg kg(-1) (wet wt.) with T&A. The results demonstrate clearly the advantage of the crop-specific exposure assessment: it can be adapted to different food baskets and allows more effective risk assessment and management of soil pollution.

Biomarkers↗
PubMed2005

The biology of exhaled nitric oxide (NO) in ischemia-reperfusion-induced lung injury: a tale of dynamism of NO production and consumption.

The main objective of this paper is to review the potential diagnostic roles of exhaled nitric oxide (NO) in evaluating ischemia-reperfusion-induced lung injury associated with cardiac surgery. We shall start by elaborating on current clinical practice of cardiac surgery and to arrive at the conclusion that clinically important ischemia-reperfusion injury is a common scenario of many forms of these surgical procedures. We shall conclude this part by establishing the clinical need for biomarkers of inflammation in cardiothoracic surgery and by proposing that exhaled NO could be an important new addition to our anaesthetic monitoring repertoire based on our expertise with exhaled breath monitoring. We shall then take a closer look at mechanisms of ischemia-reperfusion injury and will propose the role of reactive oxygen and nitrogen species as mediators and biomarkers of acute lung injury. This analysis will provide a good opportunity to highlight major potential mechanisms of altered NO production and bioactivity of NO. We shall conclude that multiple relevant mechanisms may either lead to increased production of NO or enhance consumption of NO, leaving us with the paradigm that NO maybe used either as a positive or negative biomarker of inflammation. In order to explore this dilemma further, we will investigate the predominant effect of oxidative stress on NO bioactivity in cell culture models of ischemia-reperfusion injury. We will then turn to animal models of ischemia-reperfusion injury to elucidate the ultimate effects of this condition on lung NO production and concentrations of NO in the lung. Finally, we shall complete this journey by highlighting the human relevance of these observations by reviewing our own experience at Harefield Hospital, UK, and that of others, regarding exhaled NO in ischemia-reperfusion injury associated with cardiac surgery and lung transplantation.

Animals↗
PubMed2000

Regional differences in brain monoamine oxidase subtypes in an animal model of geriatric depression: effects of olfactory bulbectomy in young versus aged rats.

Geriatric depression is often associated dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, and with poor responsiveness to antidepressants that work through inhibition of monoamine reuptake; accordingly, it has been suggested that MAO inhibitors may represent a therapeutic alternative in this group. In the current study, we evaluated expression of MAO subtypes in brain regions of young and aged rats subjected to olfactory bulbectomy (OBX), a procedure that reproduces many of the biochemical and functional changes associated with human depression. Activities of both MAO A and B were elevated in aged rats as compared to young rats in most regions, but not in the midbrain, and the OBX lesion failed to produce any change in this pattern. These results stand in contrast to the differential effects of glucocorticoids, which reduce brain MAO in young animals but induce activity in aged rats. Our results support the view that the aged brain possesses biochemical characteristics that distinguish its monoamine biochemistry from that of young brain, and that these distinctions may work in conjunction with HPA axis dysregulation to influence the etiology and therapy of geriatric depression. The use of appropriate animal models for depression and for disruption of HPA axis function can allow for the testing of potential human biomarkers (such as platelet MAO) that may serve to predict treatment outcome.

Age Factors↗
PubMed2003

Comparison of cadmium and enzyme-catalyzed nitrate reduction for determination of NO2-/NO3- in breath condensate.

BACKGROUND: Analysis of NO2-/NO3- in expired breath condensate (EBC) has been proposed as a marker of inflammation in various lung diseases. METHODS: NO2- and total NO3-/NO2- concentrations were determined in EBC collected from healthy and asthmatic subjects. The NO3- was first reduced to NO2-, and total NO2- was detected by colorimetric Griess reaction. Two methods of NO3- reduction were compared. To reduce NO3-, cadmium (600 microl EBC-macromethod) and enzyme-NADPH-nitrate reductase (60 microl EBC-micromethod) were used. RESULTS: Macromethod: Mean NO2- concentrations in EBC were 1.64 +/- 0.24 micromol/l in healthy subjects and 0.42 +/- 0.17 micromol/l in asthmatic patients. Mean total NO2-/NO3- levels were 3.64 +/- 0.43 micromol/l in healthy subjects and 3.27 +/- 0.34 micromol/l in asthmatic. Micromethod: NO2- level: 1.69 +/- 0.23 micromol/l in healthy subjects and 0.53 +/- 0.21 micromol/l in asthmatics. Total NO2-/NO3- levels: 3.56 +/- 0.37 micromol/l in healthy subjects and 3.57 +/- 1.17 micromol/l in asthmatics. Variability index was 27% and 6% for macro- and micromethod, respectively. Recovery of NO3- added to EBC was 100% for enzymatic and almost 88% for cadmium reduction. There was no correlation between total NO2-/NO3- levels determined by macro- and micromethod. CONCLUSIONS: We recommend enzymatic reduction as a better method for NO3- determination in EBC.

Adult↗