[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.

[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.

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.

Chronic repetitive transcranial magnetic stimulation enhances c-fos in the parietal cortex and hippocampus.

Repetitive transcranial magnetic stimulation (rTMS) is a novel non-invasive method with anti-depressant properties. However, the mechanism of activation on the cellular level is unknown. Twelve hours after the last chronic rTMS treatment (14 days, once per day, 20 Hz, 10 s, 75% machine output, the transcription factor c-fos was markedly increased in neurons in layers I-IV and VI of the parietal cortex and in few scattered neurons in the hippocampus of Sprague-Dawley rats. The cortical activation was not blocked by the NMDA antagonist MK-801. The increase of c-fos was not paralleled by an increased glial response and activation of cortical growth factors. Thus, it is concluded that chronic rTMS differentially activates parietal cortical layers and this might be involved in mediating anti-depressant activity in other brain areas.

Distribution of secretoneurin-like immunoreactivity in comparison with that of substance P in the human brain stem.

Secretoneurin is a peptide of 33 amino acids generated in the brain by proteolytic processing of secretogranin II which is a member of the chromogranin/secretogranin family. The distribution of this newly characterized peptide was investigated by immunocytochemistry in the human brain stem. The staining pattern of secretoneurin-like immunoreactivity was compared with that of substance P in adjacent sections. Secretoneurin-like immunoreactivity appeared mainly in dot- and fiber-like structures with densities varying from low to very high. Only a low number of secretoneurin-immunoreactive perikarya was found. Pericellular staining of both secretoneurin-immunopositive and immunonegative cells was frequently observed in the area of the central gray, in the reticular formation and in the solitary nuclear complex. The medial part of the substantia nigra pars reticulata, the nucleus interpeduncularis, the area of the central gray, the raphe complex and the inferior olive displayed a high density of secretoneurin-like immunoreactivity. Furthermore, a very prominent staining was found in the medial, dorsal and gelatinous subnuclei of the solitary tract and the dorsal motor nucleus of vagus. The substantia gelatinosa of the caudal trigeminal nucleus and spinal cord were also very strongly secretoneurin-immunopositive. The staining patterns of secretoneurin- and substance P-like immunoreactivities were to a certain extent overlapping in several areas. The highest degree of coincidence was found in the substantia gelatinosa. This study demonstrated that secretoneurin is distinctly distributed in the human brain stem. Its distributional pattern indicates a role particularly in the modulation of afferent pain transmission and in the regulation of autonomic functions.

EEG alterations in patients treated with clozapine in relation to plasma levels.

It is well known that psychotropic drugs can induce EEG alterations. Dose dependence seems established; however, there are no data concerning the impact of plasma levels. The authors investigated the influence of clozapine plasma levels on the frequency of EEG alterations. Data from 29 inpatients (18 male, 11 female, 31.7 +/- 10.2 years) receiving clozapine in a dose range between 25 and 600 mg were collected prospectively. There was no psychotropic or anticholinergic comedication. All patients had normal EEGs before taking clozapine. Fifteen patients showed pathological changes (group 2) and 14 no changes (group 1). Discriminant analysis showed that EEG changes are dependent on plasma levels (P = 0.0009, plasma levels in group 1 mean 81.6 ng/ml, +/- SD 64.6, in group 2 235.7 ng/ml, +/- 169.8). A total of 72.4% of the patients were correctly classified as having either pathological EEG changes or none by this analysis. Variables such as dose, age, sex, weight and duration of treatment were not statistically relevant. It can therefore be suggested that clozapine plasma levels are a valid indicator for the appearance of electrophysiological reactions.

Characteristics of benzodiazepine long-term users: investigation of benzodiazepine consumers among pharmacy customers.

A sample of 171 benzodiazepine (bzd) users was investigated in the pharmacy where the patients filled in their prescriptions. Of the sample, 29.8% were males and 70.2% were females. About 60% of the patients had their current prescription from a general practitioner, the rest from different specialists. 70.8% stated to take bzds on more than 3 days of the week. The mean duration of intake of the entire sample was 4.5 years. The most frequent reasons for bzd intake were sleep disturbance followed by nervousness and somatic diseases. A total of 74.9% of the patients turned out to be well informed about the potential dependence hazards of bzd long term intake, but less than half of them had been informed by the prescribing physician. In a second step it could be demonstrated by means of multiple stepwise logistic regression analysis that certain characteristic parameters differentiate long-term users and persons with signs of potential abuse and dependence from other bzd users.

Dose-related plasma levels of clozapine: influence of smoking behaviour, sex and age.

Drug monitoring in psychiatry is of increasing interest due to compliance problems, side effects of psychoactive drugs and the search for adequate dosage. In the present study, plasma levels of clozapine, as determined by high performance liquid chromatography, were investigated in 148 patients receiving a daily dose between 12.5 and 700 mg clozapine. Regression analysis revealed a linear relationship between dose and plasma concentrations. Plasma concentrations at a given dose (level divided by dose and body weight) in male patients reached only 69.3% of the concentrations in female patients (Mann-Whitney U Test P less than 0.001). When the patients were divided into smokers and non-smokers, the corresponding plasma levels were also found to be linearly dose dependent in each of the two groups. However, the average plasma concentration at a given dose was only 81.8% in smokers, compared to non-smokers. This difference was statistically significant (variance analysis P = 0.022). Dividing female patients into smokers and non-smokers, the smokers reached nearly the same plasma levels as the non-smokers. Male smoking patients reached average plasma concentrations which were only 67.9% of those of non-smokers. This difference was statistically significant (Mann-Whitney U Test P = 0.0083). The plasma levels of the different age groups at a given dose per kg body weight were compared using the Mann-Whitney U Test. Significant differences were found between group 1 (18-26) and group 4 (45-54) (P less than 0.01) and group 2 (27-35) and group 4 (P less than 0.01) showing higher plasma levels in the older age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Unusual 'spike-wave stupor' in a patient with manic-depressive psychosis treated with amitriptyline.

'Spike-wave stupor' was observed in a 58-year-old male patient with manic-depressive psychosis. Almost continuous atypical spike-wave activity was seen in conjunction with a stuporous episode with stereotyped automatism. Intravenous diazepam ended both the electroencephalographic epileptiform discharges and the clinical stupor. Before and during this episode the patient was treated with an average-dose amitriptyline monotherapy. There was no family history of epileptic seizures. The patient had had electroconvulsive therapy. The history suggests that the analeptic property of amitriptyline induced the 'spike-wave stupor' in this patient.

Distribution of secretoneurin-like immunoreactivity in comparison with that of substance P in the human spinal cord.

Secretoneurin (SN), a neuropeptide of 33 amino acids, was determined in comparison with substance P (SP) by immunocytochemistry in normal human spinal cord. The density of secretoneurin-like immunoreactivity (SN-IR) was high in the superficial dorsal horn and in the lateral column of autonomic arcs. The ventral horn displayed low to moderate density of SN-IR and prominently outlined motoneurons. The congruent distribution of SN and SP to the termination of primary afferents may indicate that SN is involved in modulation of pain.

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.

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.

Neopterin production in acute schizophrenic patients: an indicator of alterations of cell-mediated immunity.

This longitudinal study analyzed how the activation of cell-mediated immunity (CMI) was related to the severity of symptomatology in 25 acute schizophrenic inpatients (DSM-III-R, 295.31). Neopterin, which was used to monitor the activation of T-cells and macrophages, was found to be within the normal range, but the lowest neopterin concentrations were measured on day 0. By day 3, a significant increase of neopterin was observed. Compared with healthy controls, patients had significantly lower neopterin levels at baseline. The highest scores on the Clinical Global Impressions Scale and the Brief Psychiatric Rating Scale occurred on day 0 and decreased significantly over the observation period. In general, the increase of neopterin was accompanied by a decrease in psychopathological symptoms. These results' indicate that at study entry, when patients are acutely ill, activation of the CMI is reduced rather than increased. Possible pathophysiological mechanisms are discussed.

A survey of drug deaths in western Austria.

We evaluated the drug deaths in western Austria during the period from 1981 to 1991. The increase of fatal cases is partly due to a change in statistical methods and the definition of 'drug victims'. In this paper a survey is given concerning the drug deaths investigated forensically and toxicologically in our area of responsibility.

Polypharmacy in psychiatric treatment. Patterns of psychotropic drug use in Austrian psychiatric clinics.

There are great variations in the way psychotropic drugs are prescribed. Most experts are in favour of psychopharmacological monotherapy, but little is known about the extent to which it is actually practised. A survey of the psychopharmacological medication of all patients under treatment was carried out in three Austrian psychiatric clinics of various types on two separate days. A psychiatric university clinic, the psychiatric department of a general hospital and a regional mental hospital were selected for the survey. It was established that only 8% to 22% of the patients underwent psycho-pharmacological monotherapy and that the patients received 2.2 to 3.3 psychotropics on average. Five to 22% of the patients received five or more psychotropic agents. The results are presented in more detail in relation to the diagnoses of schizophrenia and depression. The rare occurence of monotherapy might be due to unsound treatment regimens in some instances, but much more to a general trend in psychiatry fostering polydrug use.

[Headache as initial symptom of schizophrenic disease]. / Le cefalee, primo sintomo nell'inizio delle malattie schizofreniche

Initial schizophrenia was observed in 15 out of 93 out-patients being treated for cephalea in a Regional Neuropsychiatrical Department. Certain abnormal phenomena in the field of consciousness and body sensations are typical of coenasthetic schizophrenia, with vital asthenia and vegetative symptoms. Cephaleas and head dysaesthesias are reported. There is no doubt that coenaesthetic schizophrenia has many points in common with latent schizophrenia; on the other hand it is also closely linked to hypochondriac depression, the syndrome of endogenous juvenile failure, certain latent depressions, hypochondriac euphoria, vegetative and endoreactive dysthmia and pseudoneurotic schizophrenia. Personal studies of stress responses in schizophrenia, and pneumoencephalographic examinations and EEG data in the active stage suggest diencephalic alteration. For diagnostic and initially therapeutic purposes, every patient with cephalea should be examined thoroughly by the psychiatrist; in this way the number of schizophrenias identified and treated will be considerably increased.

[Epidemiology of depression]. / Die Epidemiologie der Depression.

The enormous variation in values quoted in the literature concerning the occurrence of depressive diseases is caused by the lack of standardized diagnostic criteria. The difficulties of epidemiological research arise from nosological differentiation within the range of depressive diseases, from case identification and case definition. Further problems result from the limiting definitions of depressive disturbances, in respect to variations within the healthy condition on the one hand, and to signs and symptoms of other diseases, on the other hand. Moreover, it is not clear from most of the relevant epidemiological literature whether the investigation of depressive states refers to nosological diagnoses, to descriptive syndromes or to symptoms. We undertook the psychiatric investigation of the entire adult population (1337 in number) of an alpine valley. The comprehensive method of case finding in our seven-year epidemiological field study revealed an incidence of 3.9% of affective psychoses. Hence, the true prevalence rate of endogenous manic-depressive disease seems to lie somewhere between 3 and 4% of the total population. This rate is confirmed by projection of the results of other studies.

[Compulsory admission and detention at psychiatric hospitals in Tirol--a frequency analysis of 11 years]. / Zwangseinweisungen und Zwangsanhaltungen an psychiatrischen Krankenhäusern in Tirol--eine Frequenzanalyse über 11 Jahre.

Freedom and compulsion are burning questions in psychiatry, and often unsatisfactorily resolved. In this paper general aspects are discussed in the light of data obtained at the Innsbruck University Department of Psychiatry and the Mental State Hospital of Hall in Tyrol. From 1976 to 1986 364 (1.99%) patients required compulsory admission following certification by police (or civil service) doctors out of 18,207 admissions to the University Department of Psychiatry over this 11-year period. Of these patients 90 had to be jugded by a court commission with regard to further compulsory hospitalization. Most frequent reasons for compulsory admission were alcohol-related psychiatric diseases in men and endogenous psychoses in women. The data collected at the University Department are compared with the situation in the Mental State Hospital of Hall in Tyrol. Results are discussed in the light of recent literature.

[Activation of the macrophage/lymphocyte system in AIDS, ARC and AIDS risk groups]. / Die Aktivierung des Makrophagen/Lymphozyten-Systems bei AIDS, ARC- und AIDS-Risikogruppen.

Elevated neopterin levels are indicative of activation of the cellular immune system. Studies on excretion of neopterin in patients with AIDS and ARC, as well as in members of risk groups have demonstrated repeated or permanent stimulation of the immune system. This stimulation can be observed in all risk groups independent of LAV/HTLV-III infection. Additionally, in vitro replication of LAV/HTLV-III has been observed to be quantitatively greatest in activated CD4+-lymphocytes. Hence, we conclude that activation of the cellular immune system represents the central cofactor for progressive LAV/HTLV-III infection. These findings seem to contrast with most reports in the literature to date, but observations of other authors corroborate them. As consequence of these studies, therapeutic regimens using immunostimulatory strategies should be prevented in AIDS and ARC patients. Immunosuppressive treatment should be considered.