[Evaluation of new technologies by residents and staff in an institutional setting. Findings of the BETAGT project]. / Bewertung neuerer Technologien durch Bewohner und Pflegemitarbeiter im institutionellen Kontext : Befunde des Projekts BETAGT.

BACKGROUND: The aim of the substudy that was conducted as part of the project "Bewertung neuer Technologien durch Bewohner und Personal im Altenzentrum Grafenau der Paul Wilhelm von Keppler-Stiftung und Prüfung des Transfers ins häusliche Wohnen" (BETAGT) was to have residents and staff members in nursing homes with limited technological equipment complete a questionnaire about their life-long technological experiences and their general technological attitude. Furthermore, specific technological devices and systems were evaluated in terms of their potential with respect to safety, privacy, or help in decreasing burden. Data were collected using a newly developed brief questionnaire. SAMPLE AND METHODS: A total of 84 residents and 109 staff members sampled from 11 different institutions were asked about their life-long technology experiences, general attitudes towards technology as well as attitudes towards specific technological devices. Residents' opinions were assessed via brief structured interviews; a structured questionnaire was given to the staff members to complete. The technological devices to be evaluated were introduced via pictured descriptions. RESULTS: Residents and staff members showed a positive attitude towards technology. With regard to the potential of new technologies, residents and staff members expect different effects on several dimensions of quality of life. Both groups rated the potential of the dimension of safety to be highest. CONCLUSION: Contrary to widely held opinion, older adults living in institutions do not, in general, seem to be too critical about new technology. From the staff members' point of view, modern technology can be integrated into daily care routines of a nursing home, but the potentials of new technologies are considered in a very differential manner.

Demonstration of antibodies to the chitin-binding mistletoe lectin (cbML) in tumor patients before and during therapy with an aqueous mistletoe extract.

Mistletoe extracts exert immunomodulatory properties in vivo and in vitro, and these effects have been related mainly to mistletoe lectin 1 (ML-1). Recently, a new chitin-binding mistletoe lectin (cbML) has been isolated and structurally characterized in these extracts. Aim of the present study was, therefore, to evaluate whether this cbML also affects immunocompetent cells and can for instance activate B-cells to produce anti-cbML-specific antibodies. Sera from patients with different tumors who were treated with the mistletoe extract ABNOBAviscum Mali (AM) 4 for at least 18 weeks were analysed before therapy and after 3, 6, 9, 12, 18, and 24 weeks. Sera were tested by ELISA against ML-1, -3, and cbML, isolated from a single mistletoe plant collected from an apple tree (Malus domestica). Eight of the 26 patients (31%) had IgG anti-cbML antibodies already before therapy, while only four had anti-ML-1 and -3 antibodies. Of the 18 anti-cbML negative patients before therapy 54% developed these antibodies during therapy, and there was a significant increase in anti-cbML antibody titers. In contrast, anti-ML-1 or -3-antibodies developed in almost 100% of the 25 patients being negative before therapy. These data indicate that cbML can induce immunological responses in patients treated with mistletoe extracts, although it seems to have lower antigenicity. Interestingly, anti-cbML antibodies can be observed in a low incidence also in individuals, not having yet received mistletoe therapy.

Induction of antibodies to viscotoxins A1, A2, A3, and B in tumour patients during therapy with an aqueous mistletoe extract.

Mistletoe extracts exert immunomodulatory properties on immunocompetent cells of the innate as well as the specific immune system. These effects have been mainly ascribed to mistletoe lectin 1 (ML-1) present in most of the extracts. However, it became evident that also other components of these extracts may induce immunological reactions, and especially viscotoxins (VT) may be of relevance. Aim of the study was, therefore, to evaluate whether VT like ML-1 could activate B-cells and lead to the production of VT-specific antibodies. Sera from 26 patients with different tumours who were treated with the mistletoe extract ABNOBAviscum Mali (AM) 4 for at least 18 weeks were analysed before therapy and after 3, 6, 9, 12, and 18 weeks. Sera were tested by ELISA against the four viscotoxins A1, A2, A3, B, as well as against ML-1. Within the observation period twenty-four (92%) of the 26 patients developed antibodies to at least one of the four VT and 25 (96%) to ML-1. In most instances, anti-VT antibodies appeared after 6-9 weeks of treatment. The antibodies were predominantly of the IgG type belonging preferentially to the IgG1 and IgG3 subclass. IgE antibodies were found only to VT-B and to ML-1. There was no relation between the development of antibodies to VT and ML-1, and also cross-reactivity could be excluded with high probability. These data indicate that not only ML-1 but also VT induce immunological responses in patients treated with mistletoe extracts. Whether there is any relationship to the postulated anti-tumour effect of mistletoe extracts has, however, still to be evaluated.

In vivo-induction of antibodies to mistletoe lectin-1 and viscotoxin by exposure to aqueous mistletoe extracts: a randomised double-blinded placebo controlled phase I study in healthy individuals.

BACKGROUND: Several studies have been performed in tumour patients to analyse the immunological response to mistletoe extracts. Considering the fact that these extracts are given subcutaneously in most instances, the kind of application resembles a typical immunization schedule. We therefore wanted to see how those extracts act on immunocompetent cells of healthy individuals hoping that this kind of provocation test may give new informations about a more specific application of these extracts in certain diseases. SUBJECTS/METHODS: 47 healthy individuals were exposed for twelve weeks either to Iscador Quercus special (IQ) known to be rich in mistletoe lectin (ML)-1 (n = 16), to Iscador Pini (IP) being poor in ML-1 but enriched in viscotoxins (n = 15), or to placebo (physiological saline) (n = 16) in a randomised, double-blinded placebo-controlled study. Humoral immunoreactivity was analysed by measuring antibodies towards the two compounds ML-1 and viscotoxin VA2 (VA2). Sera were collected in intervals of four weeks up to week 12 and again three months after last exposure. RESULTS: None of the subjects had antibodies to ML-1 or VA2 before exposure. In week 12, anti-ML-1 antibodies of the IgG-type were found in all 16 IQ-treated individuals but only 6 of the 15 probands exposed to IP. In contrast, anti-VA2 IgG-antibodies could be detected in all individuals of both groups. The antibodies were preferentially of the IgG1 and IgG3 type while antibodies of the IgA and IgM type were produced only in a few probands. Antibodies of the IgE-type occurred only in the IQ-exposed individuals and were directed against ML-1 but not VA2. None of the probands receiving placebo developed antibodies to ML-1 or VA2. Severe side effects were not observed in any of the probands. CONCLUSIONS: These data obtained in healthy individuals clearly indicate that IQ and IP-extracts can induce antigen-specific humoral responses. They may, therefore, provide, a solid basic for the evaluation of the humoral immune response in disease states.

Presynaptic serotonin receptors and alpha-adrenoceptors on central serotoninergic and noradrenergic neurons of normotensive and spontaneously hypertensive rats.

Rat brain tissues preincubated with [3H]serotonin ([3H]5-HT) or [3H]norepinephrine ([3H]NE) were superfused in the presence of an inhibitor of serotonin or NE uptake, respectively. The electrically (3 Hz) evoked [3H]5-HT release from slices of the medulla oblongata [containing the nucleus tractus solitarii (NTS)] from Wistar rats was inhibited by 5-HT and NE, and these effects were counteracted by metitepine and phentolamine, respectively. The evoked [3H]5-HT release in slices from the cortex, medulla oblongata, and hypothalamus of 5-7-, 9-11-, and 19-22-week-old spontaneously hypertensive rats (SHR) did not differ from that in slices from age-matched Wistar-Kyoto rats (WKY). Nor was there any difference between strains for: the inhibitory effects of 5-HT and NE and the facilitatory effect of metitepine on the evoked [3H]5-HT release; the shift to the right of the concentration-response curves of 5-HT and NE by metitepine and phentolamine, respectively; the potassium (12 mM)-evoked [3H]5-HT release from cortex synaptosomes and its inhibition by 5-HT; the electrically evoked [3H]NE release in cortex slices, its inhibition by NE, and the shift to the right of the concentration-response curve of NE by phentolamine. The results provide evidence that 5-HT release in the rat brain NTS can be inhibited by 5-HT receptors and alpha-adrenoceptors. 5-HT release and its modulation by presynaptic 5-HT1 receptors and alpha 2-adrenoceptors as well as NE release and its modulation by presynaptic alpha 2-adrenoceptors do not differ between SHR and WKY rats. It may be of therapeutic relevance that according to these results the effects of 5-HT1 receptor agonists activating presynaptic 5-HT autoreceptors are not attenuated in this type of hypertension. It has been suggested that such agonists can be developed as a new class of antihypertensive drugs.

Facilitation of serotonin (5-HT) release in the rat brain cortex by cAMP and probable inhibition of adenylate cyclase in 5-HT nerve terminals by presynaptic alpha 2-adrenoceptors.

Stimulation-evoked tritium overflow was examined in superfused rat brain cortex slices (stimulus: electrical impulses; 3 Hz) and synaptosomes (stimulus: potassium 12 mmol/l) preincubated with 3H-5-HT. 1. In slices and synaptosomes, the evoked 3H overflow was facilitated by forskolin and 8-Br-cAMP, but was not affected by AH 21-132 (an inhibitor of cAMP phosphodiesterase; cis-6-(p-acetamidophenyl)-1,2,3,4,4a,10b-hexahydro-8,9-dimethoxy-2-methylbenzo [c] [1,6]-naphthyridine). In the presence of AH 21-132, the facilitatory effect of forskolin on evoked overflow was increased. 2. In slices, AH 21-132 or combined administration of forskolin plus AH 21-132 did not change the percentage of basal or evoked 3H overflow represented by unmetabolized 3H-serotonin (about 30% and 60%, respectively). 3. In slices, cocaine or 6-nitroquipazine, an inhibitor of serotonin uptake, did not influence the increase in evoked overflow produced by forskolin plus AH-21-132. Forskolin plus AH 21-132 did not alter the inhibitory effect of serotonin (examined in the presence of 6-nitroquipazine) and the facilitatory effect of metitepin (a serotonin receptor antagonist) on evoked 3H overflow, but considerably decreased the inhibitory effect of clonidine or B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo-[5,4-d]-azepine). The present results suggest that the serotoninergic nerve terminals in the rat brain cortex are endowed with an adenylate cyclase, which is negatively coupled to the presynaptic alpha 2-adrenoceptors, but is not linked to the presynaptic autoreceptors.

Effects of RU 24969 on serotonin release in rat brain cortex: further support for the identity of serotonin autoreceptors with 5-HT1B sites.

Rat brain cortex slices and synaptosomes preincubated with [3H] serotonin were used to study the effects of the 5-HT1 receptor agonist RU 24969 (5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole) on the electrically (3 Hz) evoked 3H overflow from superfused slices and the potassium (12 mmol/l)-evoked 3H overflow from superfused synaptosomes. In slices superfused in the presence of 6-nitroquipazine (an inhibitor of serotonin uptake), the electrically evoked overflow was inhibited by RU 24969 and the reference compound serotonin (maximum inhibition obtainable: by about 50 and 60%, respectively; IC25 and IC30: 33 and 150 nmol/l, respectively). The inhibitory effect of RU 24969 on the evoked overflow was attenuated by cyanopindolol (a beta-adrenoceptor blocker with antagonistic properties at 5-HT1 receptors). In the absence of 6-nitroquipazine, RU 24969 did not increase the basal efflux and tended to be more potent in inhibiting the evoked overflow than in the presence of 6-nitroquipazine. The correlation of the release-inhibiting potencies of serotonin receptor agonists with their affinities for 5-HT1B binding sites (Engel et al., 1986) was slightly improved by inclusion of RU 24969, whereas that with the affinities for 5-HT1A binding sites (which was worse than the former correlation) was not changed. In synaptosomes superfused in the presence of 6-nitroquipazine, RU 24969 inhibited the potassium-evoked overflow. The inhibitory effect of RU 24969 was antagonized by cyanopindolol, which by itself did not affect the evoked overflow. It is concluded that RU 24969 acts as a highly potent agonist (with an intrinsic activity of about 0.8) at the presynaptic serotonin autoreceptor in the rat brain cortex. Furthermore, the present results support the assumption that these receptors belong to the 5-HT1B subtype.

Serotonin release in human cerebral cortex and its modulation via serotonin receptors.

Human cerebral cortex slices were prepared from brain tissue which had to be removed in order to gain access to deep-seated tumours. Subsequent to incubation with [3H]serotonin, the slices were superfused with physiological salt solution containing paroxetine, and 3H overflow was evoked by electrical field stimulation. The evoked tritium overflow (86% of which was accounted for by unmetabolized [3H]serotonin) was abolished by tetrodotoxin or omission of calcium from the superfusion fluid. Unlabelled serotonin decreased, and the serotonin receptor antagonist metitepin increased, the evoked overflow. The inhibition produced by serotonin was antagonized by metitepin. It is concluded that serotonin release in human cerebral cortex is modulated by inhibitory serotonin receptors, which may be localized presynaptically on the serotoninergic nerve fibers themselves. There are marked similarities between human and rat brain cortex with respect to action potential-induced, Ca2+-dependent serotonin release and its modulation via serotonin receptors.

Determination of serum aspartate aminotransferase with pyridoxal 5'-phosphate in the Technicon SMAC and Du Pont aca compared and correlated with the IFCC recommended method.

Inexpensive improvements in continuous-flow analytical apparatus can eliminate some perplexing inconsistencies and limitations in the use of the Technicon SMAC instrument for measuring the activity in serum of aspartate aminotransferase (EC 2.6.1.1) in the presence of pyridoxal 5'-phosphate. In addition, a calibration procedure based on values for this enzyme obtained by a modified IFCC method can be used to calibrate both the Technicon SMAC and the Du Pont aca instruments to produce excellent correlation between the two.

GABAB receptor-mediated inhibition of serotonin release in the rat brain.

Rat brain frontal cortex or striatal slices preincubated with 3H-serotonin were superfused with physiological salt solution and tritium overflow was evoked by electrical field stimulation at a frequency of 3 Hz. 1. GABA 1 mmol/1 inhibited the evoked overflow from frontal cortex slices by about 30%. The inhibitory effect was abolished when the frequency of electrical stimulation was 10 instead of 3 Hz. Progabide and R(-)-baclofen were more potent, whereas muscimol was less potent than GABA itself in inhibiting the evoked overflow; the IC15 values of progabide, R(-)-baclofen, GABA and muscimol were 8.3, 15, 170 and greater than 320 mumol/1, respectively. S(+)-baclofen behaved as a partial agonist with a maximum inhibitory effect by about 15%. Nipecotic acid and aminooxyacetic acid were ineffective. The same held true for bicuculline, picrotoxin and diazepam. 2. Bicuculline, picrotoxin, diazepam, phentolamine and the serotonin receptor antagonist metitepin did not influence the inhibitory effect of GABA. By contrast, S(+)-baclofen attenuated the effects of GABA and R(-)-baclofen. 3. The evoked overflow from striatal slices was inhibited by GABA and progabide (IC15 values: 480 and 13 mumol/1, respectively). Nipecotic acid was ineffective. The results suggest that exogenous GABA inhibits serotonin release in the rat brain via GABAB receptors which may be assumed to be located presynaptically.

Effects of DU 24565 (6-nitroquipazine) on serotoninergic and noradrenergic neurones of the rat brain and comparison with the effects of quipazine.

Rat brain cortex slices were prepared in order to study the influence of DU 24565 (6-nitroquipazine) and quipazine on the accumulation of tritium, and to investigate the effects of DU 24565 on the electrically evoked (3 Hz) tritium overflow from slices preincubated with 3H-serotonin (3H-5-HT) or 3H-noradrenaline (3H-NA). The influence of DU 24565 and quipazine on the activity of MAO was studied in rat brain homogenates, using labelled serotonin as a substrate. In cortex slices preincubated with either 3H-5-HT or 3H-NA, DU 24565 increased the electrically evoked 3H overflow (higher potency in slices preincubated with 3H-5-HT; the percentage of 3H accounted for by unmetabolized 3H-5-HT was also increased). The facilitatory effects of DU 24565 on evoked 3H overflow were abolished when the respective monoamine uptake mechanisms had previously been blocked by citalopram and cocaine, respectively. The inhibitory effects of unlabelled 5-HT and NA on the evoked 3H overflow from cortex slices preincubated with 3H-5-HT were not altered by DU 24565. Similarly, the drug did not affect the inhibition by NA of the evoked 3H overflow from cortex slices preincubated with 3H-NA. Quipazine was a weak and non-selective inhibitor of the accumulation of 3H-5-HT and 3H-NA. DU 24565 was about 65 times more potent and about 1100 times more selective than quipazine as an inhibitor of 3H-5-HT accumulation, and it was also superior to citalopram and paroxetine in this respect.(ABSTRACT TRUNCATED AT 250 WORDS)