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Biomedical subjects

F Müller-Spahn

Publications and source records attributed to F Müller-Spahn.

At least 55 records · Page 3Linked to original sources
PubMed1998

Histological markers in nasal mucosa of patients with Alzheimer's disease.

Neuropathological changes such as dystrophic neurites and the presence of abnormal tau protein in the olfactory system, including primary sensory cells and nerve fibres have previously been demonstrated in nasal mucosa tissue of patients with Alzheimer's disease (AD). These changes were detected in autopsy-derived material from histopathologically confirmed AD cases as well as in biopsy tissue from clinical severely ill AD patients. To investigate the potential usefulness for the early diagnosis of AD, we obtained biopsy tissue from olfactory mucosa from 5 clinically mild to moderate AD patients and stained for the presence of tau or beta-amyloid by immunocytochemistry using a panel of specific antibodies. No positive staining was found in any of the cases. For comparison, post-mortem olfactory tissue from AD patients with severe neuropathological changes (widespread neurofibrillary tangles and amyloid in the brain) was investigated. In these severe cases, tau immunoreactivity was found in fine nerve fibres in the lamina propria and in a few olfactory epithelial cells. These results are consistent with other reports showing that cytoskeletal changes and tau pathology in the olfactory epithelium are not primary (or specific) features of AD and may occur predominantly in late stages of the disease.

Aged↗
PubMed1998

[The social status of schizophrenic patients].

In the German multicenter ANI study comparing continuous prophylactic treatment with intermittent medication, the social situation of a large sample of 364 schizophrenic patients was investigated and followed up over a 2-year period of outpatient aftercare. Effective therapy and prophylaxis substantially reduced relapses and rehospitalization. On the other hand, the psychosocial situation still showed considerable disadvantages. Of the patients (35 years old on average), 60% were still unmarried. Almost one-half of the patients still lived alone or with their parents, and one-third lived a very solitary life. At the end of the 2-year aftercare period, one-third was able to earn their own living. Almost one-half retired early from their occupations. Predictors and intervening variables are presented in order to stimulate early rehabilitation approaches. Schizophrenics are particularly placed at a disadvantage by tighter competition in the employment market, even though the course of illness can be improve. Social psychiatry must to be involved in helping to improve social contacts, accommodation and employment in order to prevent major distress.

Adult↗
PubMed1997

Interleukin-6 (IL-6) and soluble forms of IL-6 receptors are not altered in cerebrospinal fluid of Alzheimer's disease patients.

We quantitated interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and soluble form of the IL-6 signal-transducing protein gp130 (sgp130) in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) (n = 17) and control subjects (n = 18) using sensitive enzyme-linked immunosorbent assays (ELISA). Our results show that none of the parameters examined was significantly different in CSF of AD patients as compared to control age-matched non-demented patients. We conclude that CSF levels of IL-6 and their soluble receptors do not necessarily reflect local changes of the IL-6 system that has been shown to be involved in neurodegenerative events occurring in AD. Levels of sgp130 are substantially high (approximately 100 ng/ml) in the CSF of all individuals probably representing a high antagonistic potential.

Aged↗
PubMed1997

Decrease in parietal cerebral hemoglobin oxygenation during performance of a verbal fluency task in patients with Alzheimer's disease monitored by means of near-infrared spectroscopy (NIRS)--correlation with simultaneous rCBF-PET measurements.

We used near-infrared spectroscopy (NIRS) to study non-invasively changes in cerebral hemoglobin oxygenation in the frontal and parietal cortex during performance of a verbal fluency task in patients with Alzheimer's disease (AD). Whereas healthy elderly subjects (n = 19, age 67 +/- 10 years) showed increases in concentrations of oxygenated hemoglobin [HbO2] (mean (arbitrary units) +/- S.E.M., 1.44 +/- 0.59) and total hemoglobin [HbT] (0.92 +/- 0.81) over the left superior parietal cortex, patients with AD (n = 19, age 71 +/- 10 years) showed significant decreases in [HbO2] (-3.26 +/- 1.30, P < 0.01) as well as [HbT] (-4.45 +/- 1.57, P < 0.01). [HbR] decreased slightly in both groups (-0.62 +/- 0.29 and - 1.18 +/- 0.40, respectively). Using two pairs of NIRS optodes placed on the left superior partietal cortex and on the left prefrontal cortex simultaneous increases in [HbO2] as well as [HbT] in both cortical regions in the healthy elderly subjects (n = 8, age 60 +/- 15) were demonstrated during performance of the task. AD patients (n = 10, age 65 +/- 13 years) showed decreases in [HbO2] and [HbT] in the parietal cortex and, at the same time, increases in [HbO2] and [HbT] in the frontal cortex. Simultaneous NIRS-[HbT] and PET-rCBF measurements showed a significant correlation both when calculated in a 'banana' shaped volume approximated by using cortical thresholds as well as when calculated in a semisphere volume of brain tissue beneath the optodes placed on the head surface (patients with AD, n = 10). The correlation was dependent on the assumed penetration depth of the near-infrared light and was best for all three NIRS variables ([HbO2], [HbR] and [HbT]) when calculated using a semisphere radius of 0.45 cm to 1.35 cm. In conclusion, in Alzheimer's disease a marked reduction of regional cerebral blood flow and cerebral hemoglobin oxygenation may occur during activation of brain function, probably mainly in degenerating brain areas, such as the parietal cortex.

Aged↗
PubMed1997

Dependence of cerebrospinal fluid Tau protein levels on apolipoprotein E4 allele frequency in patients with Alzheimer's disease.

Consistent pathological hallmarks of Alzheimer's disease (AD) are the formation of brain amyloid and neurofibrillary tangles (NFTs). Levels of the major protein component of NFTs, the microtubule associated protein Tau, were shown to be increased in cerebrospinal fluid (CSF) of AD patients as compared to age-matched controls. The presence of apolipoprotein E-epsilon 4 allele (APOE4) is a risk factor for sporadic and familial late-onset AD. ApoE may interact with the binding of Tau to microtubules and Tau phosphorylation in an isoform-specific manner. We investigated whether direct evidence of an isoform-specific interaction of apoE and Tau can be demonstrated in the CSF of live AD patients. We measured the apoE genotype and CSF levels of Tau in 19 patients with probable AD and 12 age-matched control subjects. We found that CSF levels of Tau increase with increasing APOE allele frequency (Spearman rank correlation, zeta = 2.71, P = 0.007). This finding may be in agreement with reports of a lesser binding of apoE4 to Tau, compared to apoE2 and apoE3, resulting in higher levels of unbound Tau in CSF.

Aged↗
PubMed1997

[Central to decentralized admission to the psychiatric hospital. Effects of changed admission circumstances on structure and process quality].

The study provides empirical data to compare different systems used for hospital admission procedures in a psychiatric clinic. The Psychiatric University Clinic Basel replaced its traditional central admission ward by direct admission to a number of different treatment settings. This change had consequences for both structural and procedural quality. More admissions occurred after prior notice had been given, and these admissions occurred more often at a time of day when more clinic staff were available. The rate of voluntary admissions increased, and the continuity of care, as measured by the number of transfers within the clinic during the first 5 days post-admission, was improved. These findings, which support an interpretation that the treatment conditions were improved, must be balanced against the drawback of delayed decision-making processes with, for example, longer waiting times for the patient. However, the continuity of therapeutic relationships can be increased through further changes in the procedural quality.

Adult↗
PubMed1997

[Structural magnetic resonance tomography in diagnosis and research of Alzheimer type dementia].

One of the most widely used neuroimaging procedures in Psychiatry and Neurology is magnetic resonance imaging (MRI). MRI has gained the position of a standard investigation in the differential diagnosis of dementia syndromes. In the clinical diagnosis of Alzheimer's disease (AD) MRI helps to improve the diagnostical accuracy. Recently new MRI-based techniques for performing volumetric measurement of cortical and subcortical structures have been developed. First reports indicate that MRI-based volumetric measurements can be accurate in differentiating AD patients from cognitively normal elderly individuals. These new techniques may be useful adjunct in assessing the clinical diagnosis of AD. Results could also yield insight in the fundamental pathology of the degenerative disease. It is the objective of this chapter to summarize and comment on the significance of MRI in the diagnosis and research of AD. Future directions are outlined, including the use of microscopic MRI, the differentiation of white matter signal hyperintensities and the combined evaluation of structural MRI and functional imaging techniques.

Adult↗
PubMed1996

Beta 2-receptor density on mononuclear blood cells in patients suffering from neuroleptic-induced akathisia (NIA).

The effectiveness of beta-blockers in the treatment of neuroleptic-induced akathisia (NIA) suggests that beta-adrenergic overactivity is involved in the manifestation of NIA. As an approach to understanding this postulated overactivity, we investigated the beta 2-receptor density on mononuclear blood cells in 21 patients suffering from NIA as well as in 12 patients without NIA. The beta 2-receptor density in NIA-positive patients was significantly higher than that in NIA-negative patients (t = 2.84; p = .008). The NIA-positive patients were treated with 20 mg propranolol t.i.d. for 5 days. The beta 2-receptor density in treatment responders did not differ significantly from that in non-responders. Our results indicate that beta 2-receptors on mononuclear cells in patients with NIA may be of a certain degree of importance. With the prerequisites of replicability as well as correlation of this parameter with therapeutic success of beta-blockers, it may be considered as a predictor for treatment response.

Adolescent↗
PubMed1996

Near infrared spectroscopy in the diagnosis of Alzheimer's disease.

Near infrared spectroscopy (NIRS) is a new technique that permits noninvasive monitoring of cerebral blood and tissue oxygenation. Recently, we and others have shown that NIRS measurements are sensitive enough to follow changes in cerebral hemoglobin oxygenation due to activation of brain function. Based on these findings we have assessed the influence of aging as well as the influence of neurodegeneration on cerebral hemoglobin oxygenation during mental work. The typical NIRS pattern in young healthy subjects while performing calculation tasks measured in the frontal cortex were increases in oxygenated hemoglobin [HbO2] and total hemoglobin [HbT] while reduced hemoglobin [HbR] decreased. Elderly healthy subjects showed a significant lower mean increase in [HbO2] and [HbT] levels. Regression analysis revealed an age-dependent decline in activation-induced local increase of [HbO2] as well as [HbT]. Furthermore, we monitored changes in cerebral hemoglobin oxygenation in the frontal cortex while patients with probable Alzheimer's disease (AD) performed cognitive tasks. Whereas elderly healthy subjects (as well as patients with major depression, age-associated memory impairments or vascular dementia) again showed clear increases in the local concentrations of [HbO2] and [HbT] during brain activation, AD patients showed significant decreases compared to the baseline levels in both variables that were most pronounced in the parietal cortex. To clarify whether the different patterns in cerebral hemoglobin oxygenation during cognitive activation were due to an altered functional brain organization in AD or to alterations in the cerebrovascular response to neuronal activation, we are currently performing simultaneous NIRS and (015-H20-)PET measurements during performance of a cognitive task (Stroop test). Our finding of a regional reduced oxygen supply during activation of brain function may be of relevance to the development and the time course of neurodegeneration.

Aging↗
PubMed1996

Computer-based cognitive training in Alzheimer's disease patients.

Memory training programs for cognitively impaired patients have often been criticized for their lack of relevance to everyday activities. We therefore report our experience with four patients suffering from probable Alzheimer's disease, who were trained with a new computer-based program recently developed by our research group. An everyday task of personal relevance to the patient is simulated and trained on a PC-touch-screen using personal photographs of the patient's surroundings and biography. According to the degree of cognitive impairment, training has three major aspects 1) social competence in patients with beginning deficiencies, 2) orientation in patients with moderate disease, and 3) emotional aspects in patients with advanced deficiencies. The patient's training performance improved substantially. While psychopathometric tests showed no significant effects with regard to general cognitive performance, levels of motivation were high and there was a positive acceptance of the training and signs of emotional activation.

Aged↗
PubMed1996

Unstable anticoagulation in the course of amitriptyline treatment.

A potential drug-drug interaction between the tricyclic antidepressant amitriptyline and the oral anticoagulant phenprocoumon, causing intensified hypo- and/or hyperprothrombinemic effects, was investigated. In seven patients simultaneously receiving amitriptyline and phenprocoumon the course of the Quick values and the amitriptyline and phenprocoumon dosages were registered. The resulting data represented graphically was additionally compared with data and diagrams gained from a control group of seven phenprocoumon patients not receiving amitriptyline. Whereas in the control group the average Quick values (or the target International Normalized Ratio) lay within the required therapeutic range, massive fluctuations were seen in the amitriptyline-treated patients. These fluctuations did not disappear until the amitriptyline medication was discontinued. Whether our findings are actually due to a clinically relevant drug-drug interaction needs to be investigated in further controlled studies based on a larger number of patients, the more so as no comparable investigations and only few references to this subject are to be found in the literature. Should an amitriptyline influence on the frequently prescribed coumarin derivative be proven, an increased risk of rethrombosis or bleeding complications in patients receiving both amitriptyline and phenprocoumon would appear to be indicated.

Adult↗
PubMed1996

The psychobiology of the acute schizophrenic episode.

Despite intensive worldwide attempts to clarify the pathogenesis of schizophrenia many questions are still open. Evidence is accumulating to suggest that structural abnormalities in various cortical and limbic areas result at least partly from neurodevelopmental disturbances. Prenatal and/or perinatal factors are supposed to play an important role. There is a growing belief that acute schizophrenic symptomatology might be a result of deficits in the sensory filtering process at the level of the thalamus. Several neurotransmitter systems have been implicated in the pathophysiology of schizophrenia, supporting a neurotransmitter imbalance model. Dysfunctions of the dopaminergic and glutamatergic systems may be predominantly involved.

Acute Disease↗
PubMed1996

Modified oral anticoagulant potency in an amitriptyline-treated patient?

We report the case of a 74-year-old female patient who received the antide-pressant amitriptyline because of a major depression. Incidence of acute lower extremity venous thrombosis required an additional oral anticoagulant therapy with phenprocoumon. During the simultaneous adjustment of both substances, the Quick value displayed great fluctuations which only disappeared after discontinuation of the amitriptyline medication. This finding is discussed as an aspect of a possible drug-drug interaction between amitriptyline and phenprocoumon.

Aged↗
PubMed1995

Age dependency of changes in cerebral hemoglobin oxygenation during brain activation: a near-infrared spectroscopy study.

We used near-infrared spectroscopy (NIRS) to study noninvasively the influence of aging on changes in the local concentration of oxygenated hemoglobin ([HbO2]), reduced hemoglobin ([HbR]), and total hemoglobin ([HbT] = [HbR] + [HbO2]) during activation of brain function. Young subjects (n = 12; age, 28 +/- 4 years) performing calculation tasks showed an increase in [HbO2] [mean (arbitrary units) +/- SD, 2.36 +/- 1.07] and [HbT] (2.24 +/- 1.13) in the frontal cortex, while [HbR] (-0.11 +/- 0.48) decreased. Elderly subjects (n = 17; age, 52 +/- 10 years) showed a significantly lower mean increase (p < 0.05) in [HbO2] and [HbT] levels (1.21 +/- 1.38 and 0.72 +/- 1.41, respectively). Regression analysis supports the hypothesis of an age-dependent decline in the activation-induced local increase in [HbO2] (y = -0.241x + 20.062; r = -0.431, p < 0.05) as well as [HbT] (y = -0.346x + 22.496; r = -0.568, p < 0.05). We conclude that NIRS is a promising approach for studying changes in Hb oxygenation during brain activation in physiological aging.

Adult↗
PubMed1995

Reduced beta-amyloid response in lymphocytes of patients with Alzheimer's disease.

The beta-amyloid peptide (beta A4) is a principal constituent of senile plaques and is thought to play a major role in the pathophysiology of Alzheimer's disease (AD). Although the mechanism of beta-A4 neurotoxicity is still a matter of debate, one of its effects might be a destabilization of cellular calcium homeostasis, thus promoting neuronal damage. The influence of the toxic fragment beta A25-35 on the mitogen-induced rise in the intracellular calcium concentration ([Ca2+]i) in lymphocytes of AD (n = 13) and depressive patients (n = 14) as well as in healthy controls was therefore investigated (n = 16). The results showed a significant increase in the mitogen-induced calcium signal with lymphocytes of healthy controls and depressive patients. This beta A25-35-induced amplification was significantly lower in AD patients as compared to healthy controls but not as compared to depressive patients. The results thus confirm a postulated decreased beta-amyloid sensitivity in AD lymphocytes. However, this effect might not be as pronounced or as specific as recently described by Eckert et al., (1993b).

Aged↗