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Breath markers and soluble lipid peroxidation markers in critically ill patients.

Free radical-mediated inflammatory processes account for a great portion of morbidity and mortality in critically ill patients. The purpose of this study was to determine two plasma peroxidation markers and three volatile markers related to lipid peroxidation, metabolic activity and cholesterol metabolism, and to explore relationships between the different markers and patients' clinical status. Substances were analyzed in whole blood and in exhaled air in patients with head injury, acute respiratory distress syndrome (ARDS) and in those being at risk of developing ARDS. These results were compared with the baseline measurements in healthy individuals. Additionally, patients were assessed according to their inflammatory status. Concentrations of malondialdehyde and thiobarbituric acid-reactive substances in plasma as well as pentane concentrations in breath increased with increasing inflammatory status. Although these compounds are generated through peroxidation of fatty acids, concentrations of these markers were significantly different in patient groups. Isoprene concentrations were lowest in the ARDS group. Acetone concentrations were not different between patient groups. We conclude that for the assessment of lipid peroxidation and other inflammatory reactions a set of parameters has to be defined. More detailed insights into inflammatory processes can be obtained when the volatile markers and the serum markers are considered together.

Acetone↗

Short-term effect of a cultural adaptation of voluntary counseling and testing among female sex workers in China: a quasi-experimental trial.

This study evaluates the efficacy of cultural adaptation of a voluntary counseling and testing (VCT) intervention, in increasing condom use and decreasing rates of sexually transmitted diseases (STDs) among a group of female sex workers (FSWs) in Guangxi, China. This intervention is modeled after the "state-of-the-science" VCT program that was developed and evaluated by the Center for Disease Control and Prevention's Project RESPECT. Four hundred FSWs were assigned to either an intervention group receiving the VCT intervention or a control group receiving standard of care STD testing and treatment. Data were collected at baseline and 6 months postintervention. Outcome measures included HIV/STD related knowledge and perceptions, condom use, and history of STDs. Five common STDs were screened and tested through clinical examination and laboratory testing to serve as biomarkers. After controlling for potential confounders and baseline differences, the VCT intervention group was significantly higher than the control group in HIV/STD related knowledge (p < .0001) and consistent condom use with clients (odds ration [OR] = 2.23; 95% confidence interval [CI] = 1.26-3.96) at 6 months follow-up. In addition, the intervention group had a significantly lower infection rate of STDs than the control group at follow-up (OR = 0.44; 95% CI = 0.24-0.80). This quasi-experimental trial provides evidence that the brief VCT intervention, through appropriate cultural adaptation, can be efficacious in increasing condom use and reducing STD infection rate among FSWs in China.

Adult↗

Multivariate probability-based detection of drug-induced hepatic signals.

Clinical signal detection of drug-induced hepatic effects is a very inexact science. Ordinary clinical laboratory tests are the primary biomarkers for liver changes. Heuristic rules have been developed by clinicians for diagnosing liver disease and monitoring these changes. These are based on laboratory reference limits, which are also largely heuristic. This article reviews some of the statistical characteristics of univariate reference limits and shows how they can and should be extended to multivariate reference regions. For instance, in the univariate approach, the probability of a false positive cannot be specified and grows with increasing numbers of analytes evaluated. However, accurate reference regions require very large samples from reference populations. Although the uniformly minimum variance unbiased estimator can greatly improve the mean-squared-error efficiency relative to a maximum likelihood estimator, it still requires tens of thousands of reference samples to estimate the 95% reference region for 20 analytes to an order of 95 +/- 1%, for example. Methods for constructing the elliptical reference region estimators and for sample size determination are provided. It is not feasible for small laboratories to make these calculations unless more rigorous methods of standardisation can be imposed and data merged across institutions. Large healthcare systems with electronic medical records and large pharmaceutical companies singly or in collaboration could generate sufficient sample sizes for accurate reference regions if techniques to make inter-laboratory results comparable are implemented. Exiting a reference region, whether population-based or individualised, can only tell you when the patient has changed from steady state. The region into which the patient's results enter and dynamics of this change are likely to contain considerable biological information. An example of this is Hy's rule. As the number of new, expensive biomarkers grows, it may be more cost-effective to find better ways to use the data we already collect, using the new biomarkers for validation. Mathematics and computers can help do this.

Chemical and Drug Induced Liver Injury↗

Assessment of AlbuSure and its usefulness in identifying IDDM subjects at increased risk for developing clinical diabetic nephropathy.

This study, which included 154 participants in a 10-yr follow-up study of diabetes complications, was conducted to evaluate AlbuSure (a qualitative test designed to detect urinary albumin concentrations greater than 0.03 g/L) for its ability to discriminate between albumin concentrations above and below the manufacturer's concentration threshold and to identify individuals at increased risk for developing diabetic nephropathy (i.e., those with albumin excretion rate [AER] greater than 0.0288 g/24 h). The reproducibility of AlbuSure results was also evaluated. The results of these evaluations were examined by three different types of urine collections (24 h, overnight, and timed postclinic) and overall. AlbuSure's validity was examined by comparing its results to immunonephelometrically measured concentrations and AER. When compared to albumin concentration, AlbuSure had an overall sensitivity of 81.8%, specificity of 94.8%, and positive predictive value of 90.6%. AlbuSure's sensitivity was lower (71.4%) when compared with AER; however, this was higher than the sensitivity achieved by dipsticks against AER (50.7%). On testing urine samples stored for 3 days at 4 degrees C, AlbuSure results were 100% reproducible after 1 day and had an overall reproducibility of 92% after 3 days. When urine was retested after 3 and 15 mo of storage at -70 degrees C, AlbuSure was greater than or equal to 90% reproducible, with some of the differing results attributable to corresponding changes in albumin concentration. The overnight sample appeared to be the sample of choice for testing with AlbuSure in that it showed excellent reproducibility and the highest sensitivity (compared to both albumin concentration and AER).

Agglutination Tests↗

A field method for sampling toluene in end-exhaled air, as a biomarker of occupational exposure: correlation with other exposure indices.

A sensitive and rapid method for the determination of toluene in exhaled air is described. We have developed a device for direct breath sampling consisting of a sampler inserted into an empty 58 mL glass vial closed by a Teflon rubber septum. The sorbent cartridge functions as a diffusive sampler and employs a Tenax resin (300 mg, 35/50 mesh) to trap volatile organic compounds from the exhaled air. End-exhaled air is collected "in field" by removing the septum from the vial, by forcibly exhaling into the device through a suitable Teflon tube, and then by sealing the bottle quickly. Environmental toluene levels ranged from 13 to 191 mg/m3, while the concentrations of the solvent in alveolar air, in blood and urine ranged from 159 to 3354 ng/L, from 3.6 to 53.5 microg/L, and from 8.7 to 142.4 microg/L respectively. The correlation coefficients (r) of biological measurements towards environmental toluene levels were 0.822, 0.850 and 0.846 for alveolar air, blood and urine samples, respectively. The breath sampler allowed the rapid and non-invasive collection of data on elimination of toluene.

Adult↗

Is pentane a normal constituent of human breath?

Breath analysis is a non-invasive method for investigation of the volatile compounds produced by humans. Pentane has often been taken as an indicator of lipid peroxidation. Our purpose in this study was to determine its normal concentration in the breath of healthy humans. Using a specific and sensitive gas chromatography-mass spectrometry technique pentane concentrations in breath were lower than 10 pmoles/l. The high levels of pentane found by some authors in healthy humans were probably due to the coelution of pentane with isoprene, a volatile hydrocarbon present in human breath.

Adult↗

Exhaled markers of inflammatory lung diseases: ready for routine monitoring?

Assessing airway inflammation is important for investigating the underlying mechanisms of many lung diseases, including asthma and chronic obstructive pulmonary disease (COPD). Yet these are not measured directly in routine clinical practice because of the difficulties in monitoring inflammation. The presence and type of airway inflammation can be difficult to detect clinically, and may result in delays in initiating appropriate therapy. Non-invasive monitoring may assist in differential diagnosis of lung diseases, assessment of their severity and response to treatment. There is increasing evidence that breath analysis may have an important place in the diagnosis and clinical management of asthma, COPD, primary ciliary dyskinesia (PCD) and other major lung disease. The article reviews whether current noninvasive measurements of exhaled gases, such as nitric oxide (NO), hydrocarbons, inflammatory markers exhaled breath condensate (EBC) are ready for routine use in clinical practice.

Alkanes↗

Application of determined NT-proBNP in physical standardized exercise.

UNLABELLED: Natriuretic peptides can be used as markers of heart failure, its severity and also in the differential diagnosis of dyspnea. Moreover, the dynamics of natriuretic peptides in physical standardized exercise may be used in the assessment of latent heart failure. AIM OF THE STUDY: Can determination of NT-proBNP be used in the diagnosis of exercise-induced ischemia or latent heart failure? 18 probands (10 men, 8 women) under study were risk persons with unspecified ECG, without signs of manifest heart failure. They were subjected to ergometric bike exercises up to the subjective maximum, SPECT myocardium with estimated ejection fraction of the left ventricle at peak ergometric exercise. The following parameters were followed-up: a) before ergometric exercise: NT-proBNP, CRP, TNF-alpha, Hb, Htc, lactate b) at subjective maximum: NT-proBNP, Hb, Htc, lactate c) 30 min after stopping the exercise: NT-proBNP d) 60 min after stopping the exercise: NT-proBNP. The volume blood changes were taken into account (estimation from the dynamics of Htc, Hb with calculation of metabolic changes of NT-proBNP). To evaluate the dynamics of NT-proBNP, the group was divided into subgroups according to the results obtained in ergometric exercises. RESULTS: initial values of NT-proBNP within normal limits (< 59 pmol/l, 500 ng/l) in 94%, the submaximal pulse rate was reached in 94%, ischemic changes in ECG were observed in 59%, typical clinical signs of heart ischemia were recorded in 35%. Signs of heart dysfunction according to SPECT were found in 47% and ischemic symptoms were observed in 43%. In general, the plasmatic volume decreased by 24% at maximal exercise. Lactate concentration in the plasma increased in all cases. Conversion of NT-proBNP into volume blood changes revealed that increased NT-proBNP occurred only in 22%. Differences between NT-proBNP before exercises and at maximal exercise prior and after correction into volume blood changes were statistically insignificant. 30 and 60 min after the exercise, no significant differences were found in NT-proBNP concentrations. Dividing into subgroups according to the results of ergometric exercises, showed no significant differences in NT-proBNP concentrations. Dynamics of NT-proBNP changes during and after ergometric exercises cannot be used for the diagnosis of exercise-induced heart failure. The high stability of NT-proBNP related to physical activity was confirmed.

Biomarkers↗

Biochemical identification of alcohol abuse.

Biochemical test abnormality can indicate chronic alcohol abuse with good clinical sensitivity and specificity. Serum gamma glutamyltransferase and carbohydrate-deficient transferrin are the tests most frequently abnormal.

Alcoholism↗

[Expired nitric oxide concentration derived from nasal cavity and that derived from airway and lung in Japanese cedar pollinosis].

AIM: Japanese cedar pollinosis (Type I allergy to Japanese cedar pollen) shows a high incidence in spring in Japan, demonstrating symptoms such as pituita, rhinostenosis, lacrimation and sometimes pharyngeal pain. The following study investigated whether expired nitric oxide (NO) concentration is increased in Japanese cedar pollinosis, and whether expired NO concentration can be used to discriminate from cold syndrome which symptoms are similar to Japanese cedar pollinosis. SUBJECTS AND METHODS: In 20 healthy subjects, 20 patients with Japanese cedar pollinosis and 20 patients with cold syndrome, expired NO concentrations derived from nasal cavity and those derived from airway and lung were measured. Expired NO concentrations derived from nasal cavity and those derived from airway and lung were compared among the groups. RESULTS: In patients with Japanese cedar pollinosis expired NO concentrations derived from nasal cavity and those derived from airway and lung markedly increased. In patients with cold syndrome there were no significant increases in these concentrations. DISCUSSION: It is considered that expired NO concentration is useful for discriminating Japanese cedar pollinosis from cold syndrome. It seems interesting that not only expired NO concentrations derived from nasal cavity but also those derived from airway and lung were clevated. Generalized airway inflammation may be present, even without clinical asthma, in patients with Japanese cedar pollinosis.

Adult↗

[Exhaled nitric oxide as marker of inflammation in children with asthma].

The nitric oxide is a reactive gas that is produced of endogenous way by enzymes nitric oxide sintetase. Exist a great nitric oxide production induced by the isoforms of the enzyme nitric oxide sintetase, that gives as a result the products training citotoxic, they are important mediating of the defence mechanisms and of normal inflammatory response. The nitric oxide can be detected in the air exhaled in human, their concentrations are increased in patient with asthma, and after the exposition to allergens. The measurement of the exhaled nitric oxide is effected by simple methods, not invasive, to value the degree of inflammation of the air route and response to the treatment with steroids in pediatric patients.

Asthma↗

End tidal carbon dioxide monitoring in spontaneously breathing, nonintubated patients. A clinical comparison between conventional sidestream and microstream capnometers.

BACKGROUND: To evaluate the end tidal carbon dioxide estimation in nonintubated, spontaneously breathing patients using either conventional sidestream or microstream capnometers. METHODS: Patients received a regional anesthesia technique, while the end tidal carbon dioxide partial pressure (EtCO2) was sampled through a nasal cannula (Nasal FilterLine, Nellcor, Plesanton, CA, USA) and measured using either a conventional sidestream capnometer with a 200 ml.min-1 aspiration flow rate, or a microstream capnometer (NBP-75, Nellcor Puritan Bennett, Plesanton, CA, USA) with an aspiration flow rate of 30 ml.min-1. After a 20 min period with stable hemodynamic variables (systolic arterial blood pressure within +/- 20% from baseline values), the EtCO2 was randomly recorded using one of the two capnometer while arterial blood was simultaneously drawn from the radial artery and analyzed for measurement of arterial CO2 partial pressure. Afterwards the nasal cannula was connected to the other capnometer and the procedure repeated. Both the capnometer and arterial blood gas analyzer were calibrated before each studied patient according to the manufacturer instructions. The same procedure was repeated at least two times in each patient. RESULTS: A total of 120 pairs of EtCO2 and PaCO2 measurements were drawn from 30 adults (age: 69 +/- 5 years; weight: 70 +/- 10 kg; height: 160 +/- 10 cm): 60 using the conventional sidestream capnometer and 60 with the microstream one. The median arterial to end tidal CO2 tension difference was 4.4 mmHg (range: 0.28 mmHg) with the microstream capnometer and 7 mm Hg (range: 0-22 mmHg) with the conventional capnometer (p = 0.02). CONCLUSION: The microstream capnometer provides a more accurate end tidal CO2 partial pressure measurement in nonintubated, spontaneously breathing patients than conventional sidestream capnometers, allowing for adequate monitoring of the respiratory function in nonintubated patients.

Aged↗

[Changes in biochemical inflammation markers in evaluation of the effectiveness of basic chemotherapy in bronchial asthma].

AIM: To analyse informative value of monitoring of NO metabolites concentration in condensate of expired air vapor (EAVC) for definition of bronchial asthma (BA) severity and antiinflammatory effect of basic therapy. MATERIAL AND METHODS: NO metabolites concentration in EAVC was measured with Grace's reagent in 76 adults and 180 children in the course of basic therapy with flixotide, tailed, ketotiphen with intal. RESULTS: NO metabolites occurred in high concentrations in EAVC of both children and adults. These concentrations were the highest in attacks and in severe BA and were reduced by basic therapy. This effect differed with the drug and its dose, e.g. flixotide and tailed given to children for a month reduced NO metabolites close to concentrations observed in healthy subjects. Ketotiphen and intal for 6 months failed to low NO metabolites significantly. CONCLUSION: NO secretion monitoring is sensitive in assessment of respiratory inflammation in BA and is informative in assessment of effectiveness of the basic therapy. In moderate BA children on flixotide and tailed were the first to achieve normal NO secretion in the airways.

Adolescent↗

[Airway inflammatory marker].

Since asthma has been recognized as a chronic inflammatory airway disease, inflammatory markers are useful tools to show the degree of allergic airway inflammation. Asthmatic airway is characterized with infiltration of activated Th2 lymphocyte, eosinophils and mast cells/basophils. Eosinophil derived proteins such as ECP, MBP and EDN are important markers indicating eosinophilic inflammation. Histamine and tryptase are the products of mast cell/basophil activation. These markers are detected in sputum, BALF, serum and urine, and increased in asthmatics. In addition to these markers, NO concentration in exhaled air, cytokines such as IL-4, IL-5, chemokines such as RANTES, eotaxin, LTE4, MMP are inflammatory markers to indicate the quality and quantity of asthmatic airway inflammation. Assessment of these markers, therefore, contributes to better control of asthmatic symptoms with appropriate therapy.

Asthma↗

An assessment of the role of exhaled carbon monoxide in acute asthmatic exacerbations in hospitalised patients.

Exhaled carbon monoxide is a useful marker of airway inflammation in untreated asthma. Whether exhaled CO is clinically useful in steroid treated patients in a hospital setting is uncertain. We therefore studied exhaled CO as a marker of asthma severity in clinical practice. Non-smoking "acute" asthmatics (hospitalised; n=33), "stable" asthmatics (n=35), and healthy controls (n=22) were recruited. Exhaled CO, peak expiratory flow (PEF) and FEV1 were measured daily (hospitalised cases) or once only (stable outpatients). Inpatients were managed without knowledge of the results. Exhaled CO levels in acute asthmatics (initial levels), stable asthmatics and controls were similar (median=2.0 ppm, h=5.05, p=0.08). In acute asthmatics, initial exhaled CO did not correlate with duration of hospitalisation, doses of intravenous corticosteroids, doses of nebulised salbutamol, PEF (% predicted) or FEV1 (% predicted). In stable asthmatics, exhaled CO did not correlate with corticosteroid dosage, PEF (% predicted) or FEV1 (% predicted). In the setting of acute hospitalised asthma patients, exhaled CO may not add any further to clinical management. This may in part be due to prior treatment with corticosteroids.

Acute Disease↗

Effect of air diving exposure generally encountered by recreational divers: oxidative stress?

Long term effects on respiratory function have been found in air divers and have indicated the development of small-airway disease. These effects have been attributed to oxygen toxicity or to venous gas micro emboli (VGM). The airway obstructions observed in air divers raise fundamental questions about whether these alterations exist after one simulated dive. The aim of this report was to study the oxidative stress induced by brief normobaric hyperoxia (FiO2 = 0.6 for 30 min) by measuring breath-exhaled compounds. Oxidative stress was measured by pentane in the expirate of 7 subjects ventilated with hydrocarbon-free air (HFA) before and after the hyperoxic exposure. NO concentration allowed us to determine the inflammatory response in the airway. Venous blood was drawn before and after the O2 breathing period for measurements of malondialdehyde (MDA). In all seven subjects, pentane elimination rates on 60%O2 do not increase after hyperoxia. NO rates during the HFA and hyperoxic exposures are significantly increased (p < 0.05). MDA concentrations are not changed after the hyperoxic exposure. Pulmonary function parameters obtained 225 minutes after hyperoxia are not changed. These results provide evidence that a dry gas and oxygen breathing (FiO2 = 0.6) for 30 min can raise exhaled NO. Oxidative stress assessed by pentane and MDA does not exist. We conclude that dry gas and the mild, 30 minute hyperoxic exposure, frequently encountered by recreational divers may be responsible for an airway inflammation. The consequences of such chronic exposure remains to be established.

Adult↗