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Biomedical subjects

F Müller-Spahn

Publications and source records attributed to F Müller-Spahn.

At least 91 records · Page 5Linked to original sources
PubMed1987

Zotepine, a neuroleptic drug with a bipolar therapeutic profile.

Zotepine, a new tricyclic compound, was investigated in 20 schizophrenic patients in two different dosage groups. Group I (n = 8) received Zotepine in a high dosage of 270 mg +/- 37 mg/die. The other group (group II; n = 12) received a low dosage of 168 mg +/- 15 mg/die. In both groups 2 patients dropped out before the end of the treatment period because of clinical deterioration. In both groups, Zotepine manifested a rapid antipsychotic effect, good tolerability, and sedative properties during the initial days. Additionally there was a stronger positive influence on negative symptoms in the group with low dosage treatment.

Adult↗
PubMed1986

Neuroendocrine effects of clonidine in chronic schizophrenic patients under long-term neuroleptic therapy and after drug withdrawal: relations to psychopathology.

The sensitivity of the alpha-adrenergic hypothalamic pituitary system, as indicated by growth hormone (GH) release after clonidine (0.15 mg i.v.), was studied in nine chronic schizophrenic in-patients (study 1) under long-term neuroleptic (NL) therapy and after 5 days' drug withdrawal and in 17 chronic schizophrenic in-patients (study 2) under long-term NL therapy and after 12 days' drug withdrawal. GH response after 5- and 12-day drug-free periods did not differ significantly from that under NL treatment; however, it was significantly lower after 12 days' drug withdrawal (AUC: 319.9 +/- 445.5 ng/ml X min) compared to age- and sex-matched normal controls (579 +/- 611 ng/ml X min). The basal norepinephrine (NE) plasma levels under long-term NL therapy were significantly elevated in both studies (study 1:894 +/- 553 pg/ml; study 2:432 +/- 268 pg/ml) compared to controls (study 1:253 +/- 55 pg/ml, study 2:234 +/- 126 pg/ml), and were decreased significantly after 5 days' drug withdrawal compared to NL treatment. There was no significant correlation between age, duration of NL therapy, last daily dosage, psychopathology, and NE plasma levels and GH response. The data presented suggest hyposensitivity of alpha-adrenergic receptor function in the hypothalamic-pituitary axis after 12 days' drug withdrawal in chronic schizophrenics. The significantly elevated NE plasma levels under NL therapy indicate that there is no adaption mechanism, even after long-term treatment.

Adult↗
PubMed1986

Psychophysiological differentiation of two types of anxiety and its pharmacological modification by minor tranquillizer and beta-receptor-blocker.

To evaluate the influence of beta-blockers and/or minor tranquillizers on autonomic reactions during brief stress, 48 healthy subjects were randomised into 4 groups: A = 4 mg Pindolol, B = 1.5 mg Cloxazolam, C = Placebo, D = 4 mg Pindolol + 1.5 mg Cloxazolam. Subjects underwent four stress situations: Counting, noise, mental arithmetic and ergometry, each lasting 4 min with rest periods of 8 min in between. Electromyogram, finger pulse amplitude, heart rate, pulse wave velocity and electrodermal activity were recorded simultaneously on-line. Analysis of variance showed that the two drugs had significant main effects in different systems: Pindolol reduced heart rate, mainly during mental arithmetic and ergometry, Cloxazolam reduced electrodermal activity, mainly during noise. It can be concluded that different structured situations with a varying amount and type of anxiety induce different autonomic reactions; these reactions can be differentially modified by the drugs applied.

Adult↗
PubMed1986

[Psychopathologic changes in chronic schizophrenic patients following withdrawal of neuroleptics: relation to therapeutic, neuroendocrine and computer tomography variables].

The following data were obtained from 36 male chronic schizophrenics (ICD 295.6) of 47 +/- 11 years of age, treated with neuroleptics for the last 16 +/- 6 years: Age, age at first manifestation of disease, duration and dosage scheme of neuroleptic therapy and number of electroconvulsive shock treatments. Blood samples were drawn both under neuroleptic treatment and after a 12-day withdrawal of neuroleptics, for determining cortisol, prolactin, beta-endorphin and noradrenaline. Psychopathology was assessed by standard criteria via BPRS. In 27 patients CT determination was carried out to determine the breadth of the third ventricle and the ventricular brain ratio. Withdrawal of neuroleptics resulted in a marked improvement, whereas 11 patients showed pronounced deterioration of their psychotic symptoms. In respect of the entire group there was a significant improvement of anergy, while disturbances of thinking were significantly enhanced. Serum levels of beta-endorphin and cortisol increased after neuroleptic withdrawal, whereas the levels of prolactin and of noradrenaline dropped. A considerable proportion of the patients showed a distinct extension of the ventricular system, but the CT variables correlated only slight with psychopathological parameters or their changes after neuroleptic withdrawal. The other variables, too, were without clinically relevant prognostic importance compared with the psychopathological changes after neuroleptic withdrawal. These variables were e.g. demography, psychopathology, therapy and neuroendocrinology.

Adult↗
PubMed1986

Clinical and biochemical effects of nicergoline in chronic schizophrenic patients.

To investigate the potential effect of Nicergoline, an alpha-adrenolytic drug, on negative symptoms in patients suffering from chronic schizophrenia, we administered this compound to 20 male chronic schizophrenics. Patients were previously maintained on long-term neuroleptic (NL) medication. Neuroleptic treatment was discontinued for 12 days, patients were then treated with 30 mg Nicergoline per day. Under NL (A), after 12 days NL-withdrawal (B), after 15 (C) and 30 (D) days Nicergoline treatment clinical ratings (BPRS and AMDP) and stimulation with clonidine (0.002 micrograms/kg body weight) were carried out. Norepinephrine (NE), epinephrine (E), and human growth hormone (HGH) were measured before and after application. Seventeen patients finished the study, 3 dropped out. Some ratings on the AMDP and BPRS scales showed an improvement. However, this improvement was only weak and accompanied by a worsening in other subscores. The withdrawal-induced decrease in NE serum levels continued after 15 days NIC, followed by an increase after 30 days. HGH response to clonidine stimulation was only attenuated after 30 days NIC. Epinephrine, blood pressure and heart rate showed no significant changes throughout the entire study. Our data suggest that NIC in the dosage applied shows no clear and pronounced alpha-2-adrenolytic effects and no specific clinical benefits for chronic schizophrenics. Further investigations are required to evaluate its effect on alpha-1-adrenoceptors.

Adult↗
PubMed1985

Tardive dyskinesia: relation to computer-tomographic, endocrine, and psychopathological variables.

Severity of tardive dyskinesia (TD) and psychopathology of 36 chronic schizophrenic patients under long-term treatment with neuroleptics (NL) was rated during NL therapy and again 12 days after NL withdrawal. Both times serum levels of prolactin, norepinephrine, beta-endorphin, and cortisol were determined. In 27 of these patients ventricular-brain ratio, width of third ventricle, maximal width of anterior horns, distance between choroid plexus, and width of four largest sulci were also measured. Fifteen patients had no signs of TD; 14 had moderate, and 7 severe TD. TD was not related to age, age at onset of illness, duration of illness, dosage and type of neuroleptics, number of ECTs, or any endocrine variable. Psychopathology was barely related to TD, but after NL withdrawal, patients with TD tended to show more deterioration, particularly with regard to thought disorder and activation. With regard to computer-tomographic (CT) variables, patients without TD showed significantly less sulcal enlargement than those with TD. These results indicate that individual predisposition, which may have led to the development of TD, also seems to involve a higher risk of relapse after NL withdrawal.

Adult↗
PubMed1985

Neuroleptic withdrawal in chronic schizophrenia: CT and endocrine variables relating to psychopathology.

The psychopathology of 36 chronic, schizophrenic patients who had been on maintenance neuroleptics was rated during neuroleptic therapy and after 12 days of neuroleptic withdrawal. At both times, hormonal serum levels were also determined. Moreover, in 27 of these patients, ventricle-brain ratio, maximal width of the third ventricle, and sulcal widening were measured on computed tomography (CT). Neuroleptic withdrawal resulted in individually different psychopathological changes: 7 patients improved, 11 worsened. Within the whole group, thought disorder deteriorated, and anergia improved. Levels of cortisol and beta-endorphin increased; those of prolactin and norepinephrine decreased. The majority of patients showed ventricular enlargement, which was marginally related to reduced thought disorder. CT and endocrine variables were slightly related to psychopathology or psychopathological effects of neuroleptic withdrawal.

Adult↗
PubMed1984

Neuroendocrine effects of apomorphine in chronic schizophrenic patients under long-term neuroleptic therapy and after drug withdrawal: relations to psychopathology and tardive dyskinesia.

The sensitivity of the dopaminergic hypothalamic pituitary system, as indicated by growth hormone (GH) release after apomorphine (0.5 mg SC), was studied in 11 chronic schizophrenic in-patients under long-term neuroleptic (NL) therapy and after 12 and 30 days' drug withdrawal. GH peak levels after a 12-day drug-free period were significantly elevated (13.1 +/- 12 ng/ml) as compared to NL therapy (4.6 +/- 6.1 ng/ml). Controls showed a significant higher mean peak GH response (13.6 +/- 10 ng/ml) compared to chronic schizophrenic patients under long-term NL therapy. The GH response of patients with symptoms of tardive dyskinesia (TD) did not differ significantly from that of patients without signs of TD. The prolactin (PRL) serum levels under long-term NL treatment were within the normal range in male schizophrenics but decreased significantly after 12 days' drug withdrawal. The data presented indicate a reduced sensitivity of the hypothalamic-pituitary dopamine receptors under long-term NL therapy. The significant increase in GH response on day 12 probably corresponds to a readjustment from a mostly blunted GH response under NL therapy back to stimulated levels of normal controls. No supersensitivity of the pituitary dopamine receptors could be detected.

Adult↗
PubMedDate not supplied

The PHA-induced calcium signal in lymphocytes is altered after blockade of K(+)-channels in Alzheimer's disease.

Several lines of evidence indicate that alterations in intracellular calcium homeostasis with sustained elevation of free calcium ions ([Ca2+]i) might be important in the pathophysiology of Alzheimer's disease (AD). Recent studies with peripheral blood-cells have demonstrated that investigation of regulatory mechanisms in calcium homeostasis might be more promising than determining only resting or stimulated [Ca2+]i values. With respect to the importance of potassium (K+)-channels in intracellular calcium regulation we have investigated whether a potassium channel dysfunction, already demonstrated for AD fibroblasts (Etcheberrigaray et al., 1993, Proceedings of National Academy of Sciences USA, 90, 8209-8213), could be observed in circulating lymphocytes as well. Thus, we studied the influence of the K(+)-channel inhibitor tetraethylammonium (TEA) on basal and PHA-stimulated [Ca2+]i in lymphocytes from AD (n = 20), non-demented depressed patients (n = 15) and age-related healthy controls (n = 23). Preincubation of lymphocytes with 100 mmol/l TEA resulted in a 45.5 +/- 8.8% inhibition (mean +/- SD) of the PHA induced rise in [Ca2+]i in healthy controls and 37.3 +/- 11.3% inhibition in depressed patients. With lymphocytes of AD patients, this effect of TEA was significantly reduced (23.2 +/- 8.8%, p < .001). If the individual data are considered there was almost no overlap between AD patients and healthy controls, since only three (15%) AD patients responded to TEA with > 30% inhibition, but only one of the controls (5%) responded with < 30% inhibition. Besides the reduced signal-inhibition by blockade of K(+)-channels we have observed a delayed response of AD lymphocytes in [Ca2+]i rise after PHA stimulation, suggesting that functional plasticity of the cells is reduced. Although the significance and molecular basis of this K(+)-channel dysfunction are not yet determined, the presented data are of great significance because of diagnostic reasons and especially because this model thus offers a possibility to investigate functional cellular alterations in vivo.

Adult↗
PubMedDate not supplied

Prodromal states in schizophrenia.

The vulnerability-stress-coping (VSC) model is the most influential heuristic concept in understanding the course of schizophrenia, whose prodromal status still offers unsolved conceptual and methodological issues. Improved knowledge about the prodromal phase would provide a better understanding of the developing psychopathology and psychophysiology of schizophrenia and could also be of predictive value to attune therapeutic actions to the course of the illness more precisely. To shed more light on the characteristics of prodromal states, data from a German multicenter study on intermittent versus maintenance neuroleptic long-term treatment in schizophrenia (ANI study) were reanalyzed with respect to the prevalence and profile, nature, time course, and predictive value of prodromal symptoms in impending relapse. The results demonstrate that prodromes are a category of symptoms on their own, but they share variance with other symptom domains. Treatment side effects, psychotic symptoms, dysphoric mood, and social dysfunction are all associated with prodromal states--the direction of this association, however, is still to be clarified. Prodromal symptoms are also related to the neuroleptic treatment strategy and its relapse-preventive efficacy--findings that underscore neuroleptic maintenance medication in preventing both overt and subthreshold psychotic morbidity in schizophrenia.

Adult↗
PubMedDate not supplied

Interactive computer-based cognitive training in patients with Alzheimer's disease.

The present paper presents data from ten patients suffering from mild to moderate Alzheimer's disease (AD), all of whom were trained to use an interactive computer-based program. Using photographs of the patient and his or her personal surroundings, an everyday task of relevance to the patient was simulated on a PC-touch screen, which the patient was trained to operate. After three weeks of training (three to four sessions a week), the patients needed less help in performing the programs, they became faster, and eight out of ten made fewer mistakes. The results were most pronounced in patients with a poor performance at the beginning, and there was no difference between early-onset (EO) and late-onset (LO) AD patients. Although the training was generally well received, there was no evidence of a general cognitive improvement, and it remains an open question whether the results achieved with PC training can be transferred to real-life situations.

Activities of Daily Living↗
PubMedDate not supplied

Elevated response of growth hormone to graded doses of apomorphine in schizophrenic patients.

Three different dosages of apomorphine (0.003 mg/kg, 0.006 mg/kg, 0.012 mg/kg) were administered to stimulate the release of growth hormone (GH) in 16 male schizophrenic patients (age: 30.6, SD: 8.1 years) and 12 healthy male controls (age: 29, SD: 3.2 years). Results showed a significantly higher GH response (P < 0.01) after stimulation with 0.006 mg/kg apomorphine (APO). In contrast, stimulation with 0.012 apomorphine was unable to distinguish patients from normal controls. The results support the hypothesis of an increased dopaminergic receptor sensitivity in the hypothalamic-pituitary system of acute schizophrenic patients. This disturbance of dopaminergic neurotransmission could be observed only after a stimulation with low doses of apomorphine.

Acute Disease↗
PubMedDate not supplied

Cortical alterations of angiotensin converting enzyme, angiotensin II and AT1 receptor in Alzheimer's dementia.

We investigated the immunohistochemical alterations of angiotensin converting enzyme (ACE), angiotensin II and AT1 receptor in the parietal cortex in Alzheimer's dementia (AD) to reveal the contributive role of the brain renin-angiotensin system in the disease process. In controls, ACE, angiotensin II and AT1 immunoreactivities were localized to pyramidal neurons of the cortex. The staining intensity was distinctly increased in AD for all three antigens, involving predominantly cortical layer V, which may reflect the enhanced brain renin-angiotensin system activity in the disease process. In addition, a prominent perivascular ACE and angiotensin II immunoreactivity surrounding some cortical vessels in aged controls and AD patients points to an underlying microvascular pathology in the process of neurodegeneration.

Aged↗
PubMedDate not supplied

Regional pattern of hippocampus and corpus callosum atrophy in Alzheimer's disease in relation to dementia severity: evidence for early neocortical degeneration.

We used volumetric MRI and analysis of areas under receiver operating characteristic (ROC) curves to directly compare the extent of hippocampus-amygdala formation (HAF) and corpus callosum atrophy in patients with Alzheimer's disease (AD) in different clinical stages of dementia. Based on neuropathological studies, we hypothesized that HAF atrophy, representing allocortical neuronal degeneration, would precede atrophy of corpus callosum, representing loss of neocortical association neurons, in early AD. HAF and corpus callosum sizes were significantly reduced in 27 AD patients (37% and 16%, respectively) compared to 28 healthy controls. In mildly- and moderately-demented AD patients, the ROC derived index of atrophy was greater for HAF volume than for total corpus callosum area. The index of atrophy of posterior corpus callosum was not significantly different from HAF at mild, moderate or severe stages of dementia. In conclusion, these findings suggest a characteristic regional pattern of allocortical and neocortical neurodegeneraton in AD. Our data indicate that neuronal loss in parietotemporal cortex (represented by atrophy of corpus callosum splenium) may occur simultaneously with allocortical neurodegeneration in mild AD. Moreover, ROC analysis may provide a statistical framework to determine atrophy patterns of different brain structures in neurodegenerative diseases in vivo.

Aged↗
PubMedDate not supplied

Haloperidol disrupts, clozapine reinstates the circadian rest-activity cycle in a patient with early-onset Alzheimer disease.

Measurement of the circadian rest-activity cycle in a patient with early-onset Alzheimer disease for 555 days revealed marked changes in the timing and amount of nocturnal activity. After neuroleptic medication was changed to haloperidol, the rest-activity cycle became completely arrhythmic for two months, concomitant with a marked worsening of cognitive state. Circadian integrity returned together with clinical improvement when the patient was subsequently treated with clozapine. This observation suggests that the known tendency for patients with Alzheimer disease to develop sleep-wake cycle disturbances may be aggravated by a classic neuroleptic; in contrast, the atypical neuroleptic clozapine may consolidate it. Similar observations in schizophrenic patients indicate that this chronobiological finding is drug- and not illness-related.

Age of Onset↗
PubMedDate not supplied

Evidence of blood-cerebrospinal fluid-barrier impairment in a subgroup of patients with dementia of the Alzheimer type and major depression: a possible indicator for immunoactivation.

Serum and cerebrospinal fluid (CSF) from 44 patients with clinical probable Alzheimer's disease (AD) (subdivided in two groups with 18 early onset, EO, and 26 late onset, LO, cases), 10 patients with vascular dementia (VD) and 24 patients with major depression (MD) were assayed for concentrations of albumin and IgG. The severity of dementia was assessed with the Mini Mental State Examination. The CSF/serum ratio for albumin and IgG as well as the IgG index were used to evaluate blood-CSF barrier function. Various patients showed signs of blood-CSF-barrier (BCB) dysfunction and only few displayed evidence of local IgG synthesis in the central nervous system (CNS) in the AD, VD and in the MD group (IgG index > 0.7). The permeability of the blood-CSF barrier was not correlated to measures of dementia severity. Our data support the hypothesis of a BCB leakage in a subgroup of all investigated patients. Furthermore, we found a small number of patients with increased intrathecal IgG synthesis. Elevated CSF immunoglobulins combined with BCB impairment might be associated or caused by a general immune activation. Our data are in agreement with the assumption that an inflammatory process may play a role in a subgroup of patients with AD but also with MD and less likely in VD. In conclusion BCB impairment and elevated IgG immunoglobulin levels are unspecific either for AD, VD or MD.

Aged↗
PubMedDate not supplied

Elevated nitric oxide production mediates beta-amyloid-induced mitochondria failure.

Mitochondrial dysfunction has been identified in a large proportion of neurodegenerative disorders including Alzheimer's disease (AD). In addition, the involvement of nitric oxide (NO) has been implicated in the pathogenesis of AD. Thus, we investigated the effects of the Swedish double mutation (K670M/N671L) in the beta-amyloid precursor protein (APPsw) on NO levels and mitochondrial function in PC12 cells. Interestingly, APPsw PC12 cells showed increased NO levels, decreased cytochrome C oxidase activity and reduced ATP levels compared to wild-type APP bearing cells and empty vector transfected cells. On the basis of our data, we propose a hypothetical sequence of events linking amyloid beta-peptide and NO production with mitochondria failure.

Amyloid beta-Peptides↗