Breath chemical markers of sexual arousal in humans.

The chemical composition of exhaled breath was examined for volatile organic compound (VOC) indicators of sexual arousal in human beings. Participants (12-male, 12-female) were shown a randomized series of three emotion-inducing 10-min film clips interspersed with 3-min neutral film clips. The films caused different arousals: sports film (positive-nonsexual); horror film (negative-nonsexual); and erotic (sexual) that were monitored with physiological measurements including genital response and temperature. Simultaneously the breath was monitored for VOC and CO2. While some breath compounds (methanol and acetone) changed uniformly irrespective of the film order, several compounds did show significant arousal associated changes. For both genders CO2 and isoprene decreased in the sex clip. Some male individuals showed particularly strong increases of indole, phenol and cresol coincident with sexual arousal that decreased rapidly afterwards. These VOCs are degradation products of tyrosine and tryptophan, precursors for dopamine, noradrenalin, and serotonin, and therefore represent potential breath markers of sexual arousal.

Electrochemical sensor system for breath analysis of aldehydes, CO and NO.

Bulky and hyphenated laboratory-based analytical instrumentation such as gas chromatography/mass spectrometry is still required to trace breath biomarkers in the low ppbV level. Innovative sensor-based technologies could provide on-site and point-of-care (POC) detection of volatile biomarkers such as breath aldehydes related to oxidative stress and cancer. An electrochemical sensor system was developed for direct detection of the total abundance of aldehydes in exhaled breath in the ppbV level and for simultaneous determination of the airway inflammation markers carbon monoxide (CO) and nitric oxide (NO). The sensor system was tested in vitro with gaseous standard mixtures and in vivo in spontaneously breathing patients and under mechanical ventilation in an animal model. The sensor system provided in vitro and in vivo detection of trace levels of aldehydes, CO and NO. Inertness of the tubing system was important for reliable results. Sensitivity of the aldehyde sensor increased with humidity. Response time for analysis of breath samples was about 22 s and relative standard deviations of sensor amplitudes were <5%. Detection limits in the low ppbV range and a linear range of more than two orders of magnitude could be achieved for volatile aldehydes. Cross sensitivities were moderate for alcohols such as ethanol or isopropanol and negligible for other typical breath volatile organic compounds such as acetone, isoprene or propofol. In proof of concept analyses in patients suffering from lung cancer and diabetes, aldehyde and CO sensor signals differed between the groups. Elevated CO levels indicated previous smoking. In a mechanically ventilated pig, continuous monitoring of breath aldehyde concentrations in the low ppbV was realized. Cumulative aldehyde measurements may add interesting and complementary information to the conventional parameters used in clinical breath research. POC applicability, easy handling and low cost of sensors facilitate measurements in large patient cohorts.

Motion reduction and multidimensional denoising in Voltage-sensitive Dye imaging.

Optical Imaging using Voltage-sensitive Dyes is characterized by low fractional changes in fluorescent light intensity upon the application of a stimulus, which leads to slight value differences between pixels on an in-general noisy image sequence. The application of an anisotropic diffusion filtering scheme, in order to contribute to the denoising of the optical images, is proposed as one option to improve its quality and for a better understanding of the physiological processes they represent. We apply an image registration approach to compensate for motion artifacts, such that we do not need to mount a fixed cranial chamber onto the skull. In this work, electrical stimulation to the tibial nerve in a rat model was used to register evoke potentials, imaging the somatosensory cortex of the animal, which was previously stained with the RH1691 dye.

Dysfunctional cortical inhibition in adult ADHD: neural correlates in auditory event-related potentials.

In recent times, the relevance of an accurate diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adults has been the focus of several studies. No longer considered a pathology exclusive to children and adolescents, and taking into account its social implications, developing enhanced support tools for the current diagnostic procedure becomes a priority. Here we present a method for the objective assessment of ADHD in adults using chirp-evoked, paired auditory late responses (ALRs) combined with a two-dimensional ALR denoising scheme to extract correlates of intracortical inhibition. Our method allows for an effective single-sweep denoising, thus requiring less trials to obtain recognizable physiological features, useful as pointers of cortical impairment. Results allow an optimized diagnosis, reduction of data loss and acquisition time; moreover, they do not account exclusively for critical elements within clinical evaluations, but also allow studying the pathophysiology of the condition by providing objective information regarding impaired cortical functions.

Impact of inspired substance concentrations on the results of breath analysis in mechanically ventilated patients.

A well-defined relationship has to exist between substance concentrations in blood and in breath if blood-borne volatile organic compounds (VOCs) are to be used as breath markers of disease or health. In this study, the impact of inspired substances on this relationship was investigated systematically. VOCs were determined in inspired and expired air and in arterial and mixed venous blood of 46 mechanically ventilated patients by means of SPME, GC/MS. Mean inspired concentrations were 25% of expired concentrations for pentane, 7.5% for acetone, 0.7% for isoprene and 0.4% for isoflurane. Only if inspired concentrations were <5% did substance disappearance rates from blood and exhalation rates correlate well. Exhaled substance concentrations depended on venous and inspired concentrations. Patients with sepsis had higher n-pentane and lower acetone concentrations in mixed venous blood than patients without sepsis (2.27 (0.37-8.70) versus 0.65 (0.33-1.48) nmol L-1 and 69 (22-99) versus 18 (6.7-56) micromol L-1). n-Pentane and acetone concentrations in breath showed no differences between the patient groups, regardless whether or not expired concentrations were corrected for inspired concentrations. In mechanically ventilated patients, concentration profiles of volatile substances in breath may considerably deviate from profiles in blood depending on the relative amount of inspired concentrations. A simple correction for inspired substance concentrations was not possible. Hence, substances having inspired concentrations>5% of expired concentrations should not be used as breath markers in these patients without knowledge of concentrations in blood and breath.

[Can the limits of intensive care management be defined?]. / Lassen sich Grenzen intensivtherapeutischen Handelns festlegen?

Medical treatment requires more than the application of techniques and devices. Knowing the limitations of (intensive) care and respecting patients' will and dignity is as important as technical skills. Limitations of therapy may arise from medical, ethical, legal, and economic reasons. Therapy may be limited through a Do-Not-Resuscitate (DNR) order, or by withholding or withdrawal of treatment. Total withdrawal of treatment ensues from proven brain death when organ donation has been denied or has been accomplished. But legislation as well as ethics and medical science fail to define unequivocal and precise criteria for limitation of treatment. Depending on the kind of disease, its prognosis and the patient's individual situation clinical scenarios can be identified when withholding or withdrawal of treatment may be thought of. The patient's expressed or anticipated wishes play a key role in decision-making on limitation of treatment. If the patient has no more decision making capacities physicians and patient's next of kin have to determine what would be in the patient's best interest. The patient and/or his family, all attending physicians and the nursing staff have to agree when limitation of care is taken into account. Hospital guidelines and written orders will help physicians and nursing staff to manage these difficult situations. Whether treatment has been limited or not, the patient and his family deserve all our medical and psychological skills--until the end.

Analysis of volatile disease markers in blood.

BACKGROUND: The diagnostic potential of breath analysis has been limited by a lack of knowledge on origin, distribution, and metabolism of the exhaled substances. To overcome this problem, we developed a method to assess trace amounts of hydrocarbons (pentane and isoprene), ketones (acetone), halogenated compounds (isoflurane), and thioethers (dimethyl sulfide) in the blood of humans and animals. METHODS: Arterial and venous blood samples were taken from mechanically ventilated patients. Additional blood samples were taken from selected vascular compartments of 19 mechanically ventilated pigs. Volatile substances were concentrated by means of solid-phase microextraction (SPME), separated by gas chromatography, and identified by mass spectrometry. RESULTS: Detection limits were 0.02-0.10 nmol/L. Venous concentrations in pigs were 0.2-1.3 nmol/L for isoprene, 0-0.3 nmol/L for pentane, and 1.2-15.1 nmol/L for dimethyl sulfide. In pigs, substances were not equally distributed among vascular compartments. In humans, median arteriovenous concentration differences were 3.58 nmol/L for isoprene and 1.56 nmol/L for pentane. These values were comparable to pulmonary excretion rates reported in the literature. Acute respiratory distress syndrome (ARDS) patients had lower isoprene concentration differences than patients without ARDS. CONCLUSIONS: The SPME method can detect volatile substances in very low concentrations in the blood of humans and animals. Analysis of volatile substances in vascular compartments will enlarge the diagnostic potential of breath analysis.

CO(2)-controlled sampling of alveolar gas in mechanically ventilated patients.

A newly designed gas-sampling device using end-tidal CO(2) to separate dead space gas from alveolar gas was evaluated in 12 mechanically ventilated patients. For that purpose, CO(2)-controlled sampling was compared with mixed expiratory sampling. Alveolar sampling valves were easily controlled via CO(2) concentration. Concentrations of four volatile substances were determined in the expired and inspired gas. Isoflurane and isoprene, which did not occur in the inspired air, had ratios of end-tidal to mixed expired concentrations of 1.75 and 1.81, respectively. Acetone and pentane, found in both the inspired and expired air, showed ratios of 0.96 and 1.0, respectively. Precision of concentration measurements was between 2.4% (isoprene) and 11.2% (isoflurane); reproducibility (as coefficient of variation) was 5%. Because the only possible source of isoflurane and isoprene in this setting was patients' blood, selective enrichment of alveolar gas was demonstrated. By using the new sampling technique, sensitivity of breath analysis was nearly doubled.

[Importance and perspectives of breath analysis]. / Bedeutung und Perspektiven der Atemgasanalytik.

Quantitative chemical analysis of volatile constituents in exhaled gas can provide useful insights into biochemical processes in the body. Relations between the chemical composition of human exhaled air and inflammatory processes, states of high oxidative activity, inhalation or ingestion of various noxious substances as well as diseases like ARDS, pneumonia or sleep apnea have been described. Clinical interpretation of these findings, however, remains difficult because definite marker substances for certain diseases could not yet be identified, substance concentrations in the exhaled air change under various conditions, and results vary in a wide range. Because of very low substance concentrations in the exhaled air sophisticated analytical techniques are necessary. Analyses are hampered by high water content and numerous contaminants in the samples. A clear distinction has to be made between substances originating from within the patient and those coming from outside of the body. Despite all these limitations there is no doubt that relations exist between the chemical composition of human exhaled air and clinical parameters. Upcoming new analytical techniques will allow more efficient extraction and preconcentration of substances in minute concentrations. Fast track bedside analyses will shortly become possible with the introduction of miniature gas chromatographic and mass spectrometric equipment. This will open a new area for clinical and basic research.

In vivo evaluation of a new method for chemical analysis of volatile components in the respiratory gas of mechanically ventilated patients.

Using the volatile anaesthetic isoflurane as a marker substance a gas chromatographic method for analysis of exhaled gas in mechanically ventilated patients was evaluated. Twelve patients with and 10 patients without preceding isoflurane exposure and seven blank respiratory circuits were investigated. Respiratory gas was sampled at four different sites in the respiratory tubing system. Analysis of volatile components was based upon adsorption onto activated charcoal, desorption by means of microwave energy, gas chromatographic separation and flame ionisation or mass spectrometric detection. Isoflurane concentrations in the blank respiratory circuits, in the control group, and in the inspiratory limb of patients with preceding isoflurane inhalation were at the limit of detection (<10(-12) mol/l). In the isoflurane group, isoflurane concentrations in the inspiratory and expiratory limb differed considerably. Using the method described, substances at very low concentrations could be identified as originating in the patient or as coming from the gas delivery system.

Application of a new method for analysis of exhaled gas in critically ill patients.

OBJECTIVE: Application of a new method for analysis of exhaled gas in critically ill patients. DESIGN: Open study. SETTING: Surgical intensive care unit of an university hospital. PATIENTS: Thirty-seven consecutive, critically ill, mechanically ventilated patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Chemical analysis of the patient's exhaled gas was based upon substance adsorption and concentration onto activated charcoal, microwave desorption and gas chromatographic separation. Patients with acute respiratory distress syndrome (ARDS) exhaled less isoprene than those without ARDS [9.8 (8.2-21.6) vs 21.8 (13.9-41.4) nmol/m2 per min [median (95% confidence interval)], p = 0.04]. In patients who developed pulmonary infection, pentane elimination increased from 0.4 (0.0-5.4) to 2.7 (0.6-6.1, p = 0.05) nmol/m2 per min and isoprene elimination decreased from 5.2 (0-33) to 5.0 (0-17, p = 0.05) nmol/m2 per min, resulting in a significant increase in pentane/isoprene ratio from 0.1 (0-0.3) to 0.4 (0-15, p = 0.007) when compared to patients without pulmonary infection. CONCLUSIONS: The new method allows quantitative analysis of human gas samples with low substance concentrations and is well suited for clinical studies which involve the investigation of metabolic processes in the lung and the body.