Exhaled methane concentration profiles during exercise on an ergometer.

Exhaled methane concentration measurements are extensively used in medical investigation of certain gastrointestinal conditions. However, the dynamics of endogenous methane release is largely unknown. Breath methane profiles during ergometer tests were measured by means of a photoacoustic spectroscopy based sensor. Five methane-producing volunteers (with exhaled methane level being at least 1 ppm higher than room air) were measured. The experimental protocol consisted of 5 min rest--15 min pedalling (at a workload of 75 W)--5 min rest. In addition, hemodynamic and respiratory parameters were determined and compared to the estimated alveolar methane concentration. The alveolar breath methane level decreased considerably, by a factor of 3-4 within 1.5 min, while the estimated ventilation-perfusion ratio increased by a factor of 2-3. Mean pre-exercise and exercise methane concentrations were 11.4 ppm (SD:7.3) and 2.8 ppm (SD:1.9), respectively. The changes can be described by the high sensitivity of exhaled methane to ventilation-perfusion ratio and are in line with the Farhi equation.

A modeling-based evaluation of isothermal rebreathing for breath gas analyses of highly soluble volatile organic compounds.

Isothermal rebreathing has been proposed as an experimental technique for estimating the alveolar levels of hydrophilic volatile organic compounds (VOCs) in exhaled breath. Using the prototypic test compounds acetone and methanol, we demonstrate that the end-tidal breath profiles of such substances during isothermal rebreathing show a characteristic increase that contradicts the conventional pulmonary inert gas elimination theory due to Farhi. On the other hand, these profiles can reliably be captured by virtue of a previously developed mathematical model for the general exhalation kinetics of highly soluble, blood-borne VOCs, which explicitly takes into account airway gas exchange as a major determinant of the observable breath output. This model allows for a mechanistic analysis of various rebreathing protocols suggested in the literature. In particular, it predicts that the end-exhaled levels of acetone and methanol measured during free tidal breathing will underestimate the underlying alveolar concentration by a factor of up to 1.5. Moreover, it clarifies the discrepancies between in vitro and in vivo blood-breath ratios of hydrophilic VOCs and yields further quantitative insights into the physiological components of isothermal rebreathing and highly soluble gas exchange in general.

The role of mathematical modeling in VOC analysis using isoprene as a prototypic example.

Isoprene is one of the most abundant endogenous volatile organic compounds (VOCs) contained in human breath and is considered to be a potentially useful biomarker for diagnostic and monitoring purposes. However, neither the exact biochemical origin of isoprene nor its physiological role is understood in sufficient depth, thus hindering the validation of breath isoprene tests in clinical routine. Exhaled isoprene concentrations are reported to change under different clinical and physiological conditions, especially in response to enhanced cardiovascular and respiratory activity. Investigating isoprene exhalation kinetics under dynamical exercise helps to gather the relevant experimental information for understanding the gas exchange phenomena associated with this important VOC. The first model for isoprene in exhaled breath has been developed by our research group. In this paper, we aim at giving a concise overview of this model and describe its role in providing supportive evidence for a peripheral (extrahepatic) source of isoprene. In this sense, the results presented here may enable a new perspective on the biochemical processes governing isoprene formation in the human body.

Dynamic profiles of volatile organic compounds in exhaled breath as determined by a coupled PTR-MS/GC-MS study.

In this phenomenological study we focus on dynamic measurements of volatile organic compounds (VOCs) in exhaled breath under exercise conditions. An experimental setup efficiently combining breath-by-breath analyses using proton transfer reaction mass spectrometry (PTR-MS) with data reflecting the behaviour of major hemodynamic and respiratory parameters is presented. Furthermore, a methodology for complementing continuous VOC profiles obtained by PTR-MS with simultaneous SPME/GC-MS measurements is outlined. These investigations aim at evaluating the impact of breathing patterns, cardiac output or blood pressure on the observed breath concentration and allow for the detection and identification of several VOCs revealing characteristic rest-to-work transitions in response to variations in ventilation or perfusion. Examples of such compounds include isoprene, methyl acetate, butane, DMS and 2-pentanone. In particular, both isoprene and methyl acetate exhibit a drastic rise in concentration shortly after the onset of exercise, usually by a factor of about 3-5 within approximately 1 min of pedalling. These specific VOCs might also be interpreted as potentially sensitive indicators for fluctuations of blood or respiratory flow and can therefore be viewed as candidate compounds for future assessments of hemodynamics, pulmonary function and gas exchange patterns via observed VOC behaviour.

[Consensus statement "Dementia 2010" of the Austrian Alzheimer Society]. / Konsensusstatement "Demenz 2010" der Osterreichischen Alzheimer Gesellschaft.

The Austrian Alzheimer Society developed evidence-based guidelines based on a systematic literature search and criteria-guided assessment with subsequent transparent determination of grades of clinical recommendation. The authors evaluated currently available therapeutic approaches for the most common forms of dementia and focused on diagnosis and pharmacological intervention, taking into consideration the situation in Austria. The purpose of these guidelines is the rational and cost-effective use of diagnostic and therapeutic measures in dementing illnesses. Users are physicians and all other providers of care for patients with dementia in Austria.

Isoprene and acetone concentration profiles during exercise on an ergometer.

A real-time recording setup combining exhaled breath volatile organic compound (VOC) measurements by proton transfer reaction-mass spectrometry (PTR-MS) with hemodynamic and respiratory data is presented. Continuous automatic sampling of exhaled breath is implemented on the basis of measured respiratory flow: a flow-controlled shutter mechanism guarantees that only end-tidal exhalation segments are drawn into the mass spectrometer for analysis. Exhaled breath concentration profiles of two prototypic compounds, isoprene and acetone, during several exercise regimes were acquired, reaffirming and complementing earlier experimental findings regarding the dynamic response of these compounds reported by Senthilmohan et al (2000 Redox Rep. 5 151-3) and Karl et al (2001 J. Appl. Physiol. 91 762-70). While isoprene tends to react very sensitively to changes in pulmonary ventilation and perfusion due to its lipophilic behavior and low Henry constant, hydrophilic acetone shows a rather stable behavior. Characteristic (median) values for breath isoprene concentration and molar flow, i.e., the amount of isoprene exhaled per minute are 100 ppb and 29 nmol min(-1), respectively, with some intra-individual day-to-day variation. At the onset of exercise breath isoprene concentration increases drastically, usually by a factor of ∼3-4 within about 1 min. Due to a simultaneous increase in ventilation, the associated rise in molar flow is even more pronounced, leading to a ratio between peak molar flow and molar flow at rest of ∼11. Our setup holds great potential in capturing continuous dynamics of non-polar, low-soluble VOCs over a wide measurement range with simultaneous appraisal of decisive physiological factors affecting exhalation kinetics. In particular, data appear to favor the hypothesis that short-term effects visible in breath isoprene levels are mainly caused by changes in pulmonary gas exchange patterns rather than fluctuations in endogenous synthesis.

[Differences between men and women in side effects of second-generation antipsychotics]. / Neuere Antipsychotika. Unterschiede im Nebenwirkungsprofil bei Frauen und Männern.

In this review we investigate whether sex differences exist for side effects of second-generation antipsychotics. Results are based on a MEDLINE search for the years 1974 through 2005. Even if pharmacokinetics differ between females and males, significantly higher plasma levels for women have been demonstrated only for olanzapine and clozapine. Hyperprolactinaemia is mainly induced by treatment with risperidone and amisulpride, and there is evidence for more pronounced prolactin levels in females. Most studies reviewed indicate that clozapine and olanzapine are associated with more body weight gain, once more especially in female patients. Furthermore, the few published studies indicate that metabolic syndrome is more frequent in females and there are likely no gender-specific differences between the new antipsychotic medications concerning frequency and degree of acute or chronic movement disturbance. The risk of QT prolongation with torsades de pointes arrhythmia is again higher in females. In conclusion, there is some evidence of sex differences in the side effects of second-generation antipsychotics. For better understanding of the basic mechanisms in sex differences, future studies with a primary focus on this topic are required. More specific data will help to determine how these differences shall affect clinical management.

Intravenous mirtazapine is safe and effective in the treatment of depressed inpatients.

Mirtazapine is a third-generation antidepressant with a dual mode of action. The oral administration has been shown to be effective and safe in the treatment of depressed patients. In this multicenter naturalistic study, we assessed the safety, tolerability, and therapeutic efficacy of intravenously administered mirtazapine in 80 moderately to severely depressed inpatients during a treatment period of 14 days. We found a significant decrease of the Hamilton Depression Rating Scale total score compared to baseline. Side effects were mild and transient. Our data indicate that intravenous mirtazapine is an effective, safe and well-tolerated treatment for depressed inpatients.

[Etiopathogenetic theories in historical concepts of schizophrenia]. / Theorien zur Atiologie in den verschiedenen historischen Schizophreniekonzepten.

In the years between 1800 and 1914, the real beginning of the twentieth century, different etiological theories and models were developed about illnesses which we today know as schizophrenic disorders. Particularly in the German speaking world, in the first third of the nineteenth century many of these followed a religious metaphysical paradigm. Those who paved the way for modern psychiatry represented an etiological concept with varying emphasis on brain pathological, hereditary-degenerative or psycho-dynamic as well as sociogenic perspectives. It has become apparent that psychiatry was always in danger of giving way to reductionist approaches. Every reductionism emphasises merely partial truths. The systemic perspective teaches us that many points of view do not contradict each other but rather compliment each other.

[Gender differences in cognitive functions]. / Geschlechtsunterschiede kognitiver Leistungen -- populärwissenschaftliche Stereotypien oder evidenzbasierte Studienergebnisse?

Gender differences in neuropsychological functioning of patients with psychiatric disorders have been studied extensively in the last years. The available studies provide conflicting results, which can be attributed to the complexity of variables influencing cognitive sex differences. In this article we review the literature about gender differences in cognitive functions in healthy men and women and discuss the relevance of hormones, socio-cultural factors, educational factors and training on the occurrence of these sex differences. Furthermore we summarize the results from functional MRI experiments, which is a useful tool for noninvasively localizing areas in the brain involved in specific cognitive functions.

Gender differences in health-related quality of life on admission to a maintenance treatment program.

We compared the gender differences in health-related quality of life (QOL) on admission to a maintenance program. 103 opioid users (65 men and 38 women) admitted to a maintenance treatment program during 2000-2002 were studied. During this period we assessed the QOL status using the German version ('Berlin Quality of Life Profile') of the Lancashire Quality of Life Profile. Physical symptoms were measured using the Opioid Withdrawal Scale. 312 urine screening tests were carried out to evaluate consumption. The female group showed significantly less additional consumption of other opiates (p = 0.043) compared with the male group. The male group showed significantly better QOL scores in self-esteem (p = 0.015), psychical health (p = 0.027), and law and security (p = 0.008). The outcome measures for withdrawal scores showed significantly less symptoms for males in twitching of muscles (p = 0.034), vomiting (p = 0.002), depressions (p = 0.004) and poor appetite (p = 0.008). In summary, both genders showed only a few significant differences on admission in terms of QOL and physical symptoms. The predominant effects of drug use appear to eclipse the gender-related role pattern. Further exploration of gender and QOL could have important theoretical and treatment implications.

No benefit derived from repetitive transcranial magnetic stimulation in depression: a prospective, single centre, randomised, double blind, sham controlled "add on" trial.

Repetitive transcranial magnetic stimulation (rTMS) has been reported to demonstrate slight effects in the treatment of depression. Hence, a novel bilateral versus unilateral and sham stimulation design was applied to further assess rTMS' antidepressant effects. Forty one medication free patients with major depression, admitted to a psychiatric unit specialising in affective disorders, were consecutively randomised into 3 groups. Group A1 (n = 12) received unilateral active stimulation consisting of high frequency (hf) rTMS over the left dorsolateral prefrontal cortex (LDLPC) and subsequent sham low frequency (lf) rTMS over the right dorsolateral prefrontal cortex (RDLPC). Group A2 (n = 13) received simultaneous bilateral active stimulation consisting of hf-rTMS over the LDLPC and lf-rTMS over the RDLPC. Group C (n = 13) received bilateral sham stimulation. Stimulation was performed on 10 consecutive workdays. All patients received antidepressant medication on the first day of stimulation, which was continued during and after the stimulation period. As no significant difference in antidepressant outcome between group A1 and A2 was found, the two groups were pooled. The time course of the outcome variables Hamilton depression rating scale (HDRS(21)) and Beck depression inventory (days 0, 7, 14, 28) by repeated measures analysis of variance revealed no significant group differences (in terms of a group by time interaction), whereas there was a significant effect of time on all three outcome variables in all groups. The results suggest that rTMS as an "add on" strategy, applied in a unilateral and a bilateral stimulation paradigm, does not exert an additional antidepressant effect.

Quality of life of HIV-infected patients: psychometric properties and validation of the German version of the MQOL-HIV.

OBJECTIVE: To determine the psychometric properties of the recently developed German version of the Multidimensional Quality of Life Questionnaire for HIV/AIDS (MQOL-HIV) and to test its performance in a sample of HIV-infected patients. METHODS: Two-hundred and seven outpatients with HIV/AIDS were interviewed with the German version of the MQOL-HIV; 109 patients were interviewed a second time approximately 2 weeks later. Patients also completed the Beck Depression Inventory (BDI) and the World Health Organization Disability Assessment Schedule II (WHODAS II). RESULTS: The German version of the MQOL-HIV showed satisfactory internal consistency (r: 0.74-0.85, sexual functioning: r = 0.61) and test-retest reliability in most subscales (r: 0.74-0.89, medical care: r = 0.67). Convergent validity with WHO-DAS II and BDI was satisfactory for most domains. Exploratory factor analysis yielded a seven-factor solution with separate factors for physical, emotional, cognitive, social and financial aspects, sexual functioning and medical care. CD4 count and source of infection were associated with most QOL domains, whereas age and gender showed no major impact on QOL. High rates of missing values were seen in the partnership domain and substantial ceiling effects in the area of medical care. CONCLUSIONS: Overall the German version of the MQOL-HIV showed satisfactory reliability and validity. However, the domains of partnership, sexuality and medical care should generally receive more emphasis in future research on QOL assessment in patients with HIV/AIDS and the MQOL-HIV may be improved in these domains.

Buprenorphine versus methadone maintenance treatment in an ambulant setting: a health-related quality of life assessment.

BACKGROUND: To compare the effects on quality of life (QOL) of oral methadone with sublingual buprenorphine. METHODS: We performed an open-label, non-randomized, two-site (methadone-buprenorphine) study. During 6 months we assessed the quality of life status of 53 opioid-dependent patients admitted to a methadone or buprenorphine maintenance programme using the German version (Berlin Quality of Life Profile) of the Lancashire Quality of Life Profile. Physical symptoms were measured using the Opioid Withdrawal Scale. Five hundred and thirty urine screening tests were carried out randomly to detect additional consumption. RESULTS: Sixty-seven opioid-dependent subjects (38 on methadone and 29 on buprenorphine) were enrolled in the study, and 53 completed it (30 subjects treated with buprenorphine and 23 subjects with racemic methadone). The subjects were comparable on all baseline measures. At the first follow-up (week 8), the buprenorphine-maintained group showed significantly less additional consumption of opioids (P = 0.013) compared with the methadone group. Patients retained in the buprenorphine or methadone programme (week 24) showed no significant differences in all quality of life scores. At the end of the study period, the buprenorphine-maintained group showed significantly less additional consumption of opioids (P = 0.001) and cocaine (P = 0.018) compared with the methadone group. The outcome measures for withdrawal symptoms after 24 weeks of treatment with buprenorphine showed slight advantages in stomach cramps, fatigue or tiredness, feelings of coldness and heart pounding. CONCLUSIONS: These results suggest that buprenorphine treatment is as effective as methadone regarding effects on quality of life and withdrawal symptoms. Buprenorphine has the potential to reduce the harm caused by drug abuse. Further research is needed to determine if buprenorphine is more effective than methadone in particular subgroups of patients.

[Placebo-controlled antidepressant drug trials. Considering the ethical implications]. / Plazebokontrollierte Antidepressiva-Studien. Uberlegungen zur Frage der ethischen Beurteilung.

For the approval of a new antidepressant for clinical use drug authorities still demand the proof of a significantly superior efficacy of the compound over placebo shown in controlled comparison studies. On the other side serious ethical concerns have been raised upon the use of placebos in clinical trials with depressed patients in that this would implicitly mean a withholding of an efficacious treatment from patients in the control groups of such trials. This article summarises frequently quoted arguments for and against placebo use in antidepressant clinical trials focussing on the specific issues involved in the therapeutic effect of antidepressants and placebos in depressed patients and discusses measures that might contribute to study designs that may better evaluate the true efficacy of a new drug while keeping the risk for the individual patient at the lowest possible level. A worldwide solution of the problem is clearly called for. A ban of placebos in antidepressant trials as it might be derived from the Declaration of Helsinki should be postponed until antidepressants with a more convincing superiority over placebo have been developed.

Pharmacological treatment strategies of residential primary care providers in dementia diseases--results of a representative survey in western Austria.

OBJECTIVE: The goal of this study was to investigate pharmacological treatment strategies used by residential primary care providers for patients with dementia. METHODS: A postal questionnaire survey was sent to all residential primary care providers, internists, neurologists and psychiatrists (n = 689) in the western region of Austria. RESULTS: The response rate (53 %) was similar in all four physician groups. Acetylcholinesterase inhibitors are considered to have a higher efficacy (p < 0.0005) compared to nootropic drugs. However, the vast majority of primary care providers (95 %) prescribe nootropic drugs. Two thirds (64 %) of the primary care providers prescribe acetylcholinesterase inhibitors. The dementia subtype influences the prescription frequency of acetylcholinesterase inhibitors, but not the specific choice of nootropic compound. Half of the primary care providers (52 %) combine antidementia drugs. Nearly two-thirds (62 %) of all primary care providers frequently prescribe antidepressants. Specific serotonin reuptake inhibitors are applied by the majority of primary care providers (96 %). About one-third (39 %) of primary care providers and internists (29 %) prescribe tricyclic antidepressants. Antipsychotics are applied frequently by around a quarter (29 %) of all physicians. More than half of primary care providers (62 %) and internists (58 %) treat patients with typical antipsychotics. Psychiatrists and neurologists are significantly more reluctant to prescribe tricyclic antidepressants and typical antipsychotics. CONCLUSIONS: Despite the lack of scientific evidence, residential primary care providers combine antidementia drugs very frequently. Therefore, controlled studies on combination therapies are urgently needed; in contrast to neurologists and psychiatrists, primary care providers and internists frequently prescribe tricyclic antidepressants and typical antipsychotics. The reasons for this should be clarified in further studies.

Magnetic stimulation induces neuronal c-fos via tetrodotoxin-sensitive sodium channels in organotypic cortex brain slices of the rat.

Repetitive transcranial magnetic stimulation is a novel non-invasive method with antidepressant properties, where electromagnetic fields are applied via an electrode. The aim of the present study was to investigate in an in vitro model if magnetic stimulation may activate the transcription factor c-fos. Organotypic brain slices of the parietal cortex were cultured for 2 weeks and then treated with a magnetic stimulator. Immunohistochemistry was used to detect c-fos like immunoreactivity. We show that magnetic stimulation (1 Hz, 10 min, 75% machine output/magstim 200 rapid stimulator) transiently enhanced c-fos 3-6 h after stimulation. Co-localization experiments revealed that c-fos was expressed in neurons but not astroglia. The activation of c-fos by magnetic stimulation was inhibited by the sodium-channel blocker tetrodotoxin (TTX) (10 microM). It is concluded that magnetic stimulation induces neuronal c-fos via TTX-sensitive sodium channels in organotypic cortex slices.

[Attempts to overcome the stigma of schizophrenia]. / Das Stigma der Schizophrenie: Versuche zu dessen Uberwindung.

The results of research into attitudes show clearly that the knowledge, the attitudes and views of our society towards psychiatric topics strongly influence practical psychiatric services. Those affected report that they are confronted with a high degree of prejudice and exclusion which considerably inhibits their recovery, their integration and their quality of life even today. Especially people with schizophrenic illnesses are affected by stigmatisation and exclusion. These are not just caused by a lack of information. Prejudices and misconceptions are deeply rooted in our cultural tradition. The negative consequences for the treatment and way of life of those affected are such that Asmus Finzen spoke of a "second illness" which may be caused by stigmatisation.Set against the background of the vulnerability-stress-paradigm, the social consequences can result in stressors. Disadvantages in terms of societal participation, negative assessments and humiliating discrimination can undermine self-esteem, ability to cope and compliance and thereby hinder the recovery process and strengthen remaining marks of the illness. Since there is extensive informed understanding about these problems, the discussion focuses increasinlgy on questions about what psychiatry and those working in psychiatry can contribute to reverse this negative attitude. This is the aim, for example, of the World Psychiatric Association's international awareness campaign, which uses modern communication techniques to try to counter the myths and misunderstandings surrounding the schizophrenic illness and its name. The study being introduced here was carried out in conjunction with the Society for Mental Health Tyrol. It was attempted to discover how information should be conveyed in order to change the attitudes of school pupils. On the basis of these results, we have begun to offer information sessions in schools throughout the Tyrol.