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F Müller-Spahn

Publications and source records attributed to F Müller-Spahn.

At least 37 records · Page 2Linked to original sources
PubMed2000

Increased CSF levels of nerve growth factor in patients with Alzheimer's disease.

The authors quantitated CSF levels of nerve growth factor (NGF) in patients with AD, nondemented control subjects (CTR), and age-matched patients with major depression (DE). CSF levels of NGF were markedly higher in the AD group than in both the CTR and DE groups (p < 0.01 and p < 0.001). Increased CSF levels of NGF in AD patients may reflect reported accumulation of NGF in the AD brain and may constitute a candidate marker for clinical diagnosis and therapeutic monitoring.

Adult↗
PubMed2000

Serum iron and ferritin in acute neuroleptic akathisia.

Acute akathisia is a common and disturbing side effect of classic antipsychotic medication. Some evidence suggests a role for iron deficiency in chronic and tardive akathisia. In acute akathisia, however, the data are contradictory. Serum iron and ferritin levels of 33 inpatients with acute akathisia during classic neuroleptic medication were compared with those of 23 patients on classic neuroleptics without this side effect. Akathisia was rated by means of the Hillside Akathisia Scale. The groups were balanced for age (mean 38.5+/-14.5), medication (butyrophenone- and phenothiazine-derived neuroleptics) and diagnosis (schizophrenia, schizoaffective disorder, psychotic affective disorder). Patients with acute akathisia had significantly lower serum ferritin levels than the patients in the control group. However, the ferritin (56. 94+/-39.54 ng/ml) and iron (88.52+/-40.0 mg/dl) levels in these patients were within the normal range (ferritin 30-300 ng/dl, iron 80-180 mg/dl). No correlations between serum iron or ferritin and akathisia ratings could be found. Although some reduction in serum ferritin was found in patients with acute akathisia compared to patients without akathisia, the difference was small and the ferritin levels were within the range of the normal population. These findings suggest a minor role for iron deficiency in acute akathisia.

Adult↗
PubMed2000

Alzheimer's disease, depression and normal ageing: merit of simple psychomotor and visuospatial tasks.

INTRODUCTION: A brief psychometric test battery was used to differentiate Alzheimer's disease (AD) patients from patients with depression and healthy age-matched control subjects. The purpose was to investigate the discriminative value of simple psychomotor and visuospatial tasks that were implemented in a computer-assisted test battery. METHODS: Manumotoric coordination, discrimination reaction time and performance on a visuospatial pattern-matching task were assessed. Subjects were 30 patients with the diagnosis of probable AD (mild to moderate), 22 patients with a major depression and 15 healthy normal control subjects. RESULTS: Discrimination reaction time separated the three groups most distinctly, but general level of cognitive functioning was a significantly confounding variable. There were no differences between the AD and the depressed patients when the MMSE was used as a covariate. Substantial deficiencies in manumotoric coordination were found in both demented and depressed patients. The visual pattern-matching task yielded longer reaction times in both patient groups than in the control group. CONCLUSION: Translated into neuropsychological terms, these data suggest deficiencies in basic central operations, a slowing of central information processing and attentional deficits in AD and depressed patients. Psychomotor tasks were able to distinguish effectively healthy elderly persons from AD and depressed patients. This test battery, however, appears to be limited in differentiating AD from depression.

Aged↗
PubMed2000

Inhibition of phenprocoumon anticoagulation by carbamazepine.

Carbamazepine inhibits warfarin and dicoumarol anticoagulation through induction of cytochrome P450-enzymes. Inhibition of phenprocoumon anticoagulation by carbamazepine has been supposed in some reviews, however, without hard empirical evidence. We report a patient who was anticoagulated with phenprocoumon in whom carbamazepine produced a dramatic increase in prothrombin time ratio (Quick). After discontinuation of carbamazepine, Quick-values returned to therapeutic levels. Valproate did not affect phenprocoumol's anticoagulant properties. The potentially hazardous carbamazepine-phenprocoumon interaction should be emphasized in reference drug manuals.

Anticoagulants↗
PubMed2000

Increased cerebrospinal fluid levels of neurotrophin 3 (NT-3) in elderly patients with major depression.

Neurotrophin 3 (NT-3) is a member of the neurotrophin gene family which supports the survival of specific neurons. NT-3 was shown to prevent the death of adult central noradrenergic neurons in vivo, a neuronal population which is associated with the pathophysiology of major depression. We quantitated CSF levels of NT-3 in elderly patients with major depression (DE) and compared them to patients with Alzheimer's disease (AD), and mentally healthy control subjects (CTR). CSF levels of NT-3 were markedly and significantly elevated in the DE group, as compared to either the AD or the CTR group (P < 0.01, and P < 0.001, respectively). In terms of diagnostic accuracy, measurement of NT-3 levels in DE resulted in 73.9% sensitivity, and 89.7% specificity. Increased CSF levels of NT-3 may indicate a disturbance of the central noradrenergic system in patients with DE. NT-3 may constitute a biochemical candidate marker for clinical diagnosis and for the evaluation of therapeutic strategies in DE.

Adult↗
PubMed2000

Mercury induces cell cytotoxicity and oxidative stress and increases beta-amyloid secretion and tau phosphorylation in SHSY5Y neuroblastoma cells.

Concentrations of heavy metals, including mercury, have been shown to be altered in the brain and body fluids of Alzheimer's disease (AD) patients. To explore potential pathophysiological mechanisms we used an in vitro model system (SHSY5Y neuroblastoma cells) and investigated the effects of inorganic mercury (HgCl2) on oxidative stress, cell cytotoxicity, beta-amyloid production, and tau phosphorylation. We demonstrated that exposure of cells to 50 microg/L (180 nM) HgCl2 for 30 min induces a 30% reduction in cellular glutathione (GSH) levels (n = 13, p<0.001). Preincubation of cells for 30 min with 1 microM melatonin or premixing melatonin and HgCl2 appeared to protect cells from the mercury-induced GSH loss. Similarly, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assays revealed that 50 microg/L HgCl2 for 24 h produced a 50% inhibition of MTT reduction (n = 9, p<0.001). Again, melatonin preincubation protected cells from the deleterious effects of mercury, resulting in MTT reduction equaling control levels. The release of beta-amyloid peptide (Abeta) 1-40 and 1-42 into cell culture supernatants after exposure to HgCl2 was shown to be different: Abeta 1-40 showed maximal (15.3 ng/ml) release after 4 h, whereas Abeta 1-42 showed maximal (9.3 ng/ml) release after 6 h of exposure to mercury compared with untreated controls (n = 9, p<0.001). Preincubation of cells with melatonin resulted in an attenuation of Abeta 1-40 and Abeta 1-42 release. Tau phosphorylation was significantly increased in the presence of mercury (n = 9, p<0.001), whereas melatonin preincubation reduced the phosphorylation to control values. These results indicate that mercury may play a role in pathophysiological mechanisms of AD.

Amyloid beta-Peptides↗
PubMed2000

Alterations in trk A, trk B and trk C receptor immunoreactivities in parietal cortex and cerebellum in Alzheimer's disease.

The neurotrophins nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 bind to the tyrosine kinase (trk) receptors trk A, trk B and trk C, respectively, with high affinity. We investigated the expression of the trk receptors in the parietal cortex (PC) and cerebellum of patients with Alzheimer's disease (AD) and age-matched controls. Cortical layers II-VI displayed a distinct cellular immunoreactivity for trk A and C with an emphasis in the pyramidal neurons of layers III and V. Trk B immunoreactivity was primarily located in the deeper cortical layers with a predominance in layer V. There was a decrease in trk A and C immunoreactivity in the PC of AD cases, while trk B density appeared to be unchanged. In addition, cerebellar Purkinje cells revealed a distinct immunoreactivity for trk C both in control and AD cases, suggesting trk C may be important in the maintenance of these cells in the aged brain.

Aged↗
PubMed2000

Review of quetiapine and its clinical applications in schizophrenia.

Preclinical studies have shown that quetiapine (Seroquel, AstraZeneca) is an atypical antipsychotic with many similarities to clozapine. Both placebo-controlled and comparative studies in patients with schizophrenia have demonstrated that quetiapine has long-term efficacy in both positive and negative domains, as well as beneficial effects on affective and cognitive symptoms. Comparative clinical studies confirm that quetiapine is at least as effective as the standard antipsychotics, chlorpromazine and haloperidol and response rates with quetiapine are similar to those reported with other atypical antipychotics. Quetiapine has also demonstrated superior efficacy to haloperidol in partially responsive patients, who can be particularly difficult to treat. Quetiapine has a wide clinical dosing range (150-750 mg/day), although doses of 400 mg or above should be used in patients who do not fully respond to lower doses of the drug. Quetiapine is generally well tolerated with no requirement for routine ECG or blood monitoring and it has minimal effects on weight. Uniquely among other first-line atypical antipsychotics, quetiapine is associated with a placebo-level incidence of EPS and an indistinguishable effect from placebo on plasma prolactin at all doses. Thus, clinicians can confidently increase the dose of quetiapine, without increasing the risk of EPS or hyperprolactinaemia. A number of studies have also shown that quetiapine is well-tolerated and effective in patients who are particularly susceptible to EPS, including elderly and adolescent patients and those with pre-existing dopaminergic pathology, such as Alzheimer's disease and Parkinson's disease. The consistent efficacy in treating all schizophrenic domains and good tolerability, particularly placebo-level EPS, make quetiapine acceptable to patients, as demonstrated in a survey of patient satisfaction. Thus quetiapine is a suitable first-line therapy for the treatment of schizophrenia and psychosis.

Antipsychotic Agents↗
PubMed1999

Risk factors and differential diagnosis of Alzheimer's disease.

Due to demographic changes the frequency of dementia is increasing dramatically. About 50-60% of patients with dementia are clinically associated with AD, which is a multifactorial and long-term disease both in clinical and preclinical aspects. Various genetic and non-genetic risk factors play a role in influencing age of onset and disease progression.

Aged↗
PubMed1999

[Psychotropic drugs].

With the introduction of the antipsychotic compound Chlorpromazine in the early 1950s began the era of psychotropic drugs. These include a large number of different classes of compounds. They have been clearly demonstrated to be more effective than placebo in the treatment of psychiatric disorders. Anxiolytic and hypnotic drugs are the most commonly prescribed agents. In the past decade many new antidepressants and antipsychotics with a more favorable side-effect profile have been introduced onto the market, and have dramatically widened our possibilities to improve the course of the various psychiatric disorders. The administration of psychotropic drugs is primarily syndrome-related. So far, specific causal therapy is not available.

Antidepressive Agents↗
PubMed1999

ELISA-quantitation of phosphorylated tau protein in the Alzheimer's disease brain.

A reliable, sensitive and specific sandwich ELISA for the quantitation of paired helical filament (PHF) tau in human brain was developed using well-defined monoclonal antibodies. We examined rapid-autopsy-derived brain tissue from 21 neuropathologically confirmed Alzheimer's disease (AD) patients and 14 nondemented controls, matched for age, sex and postmortem delay times. We demonstrated significant elevations of phosphorylated tau levels in the frontal and parietal cortex as well as in the hippocampus of AD patients as compared to the nondemented controls. No difference was observed in the cerebellum. Phosphorylated tau levels measured by ELISA were significantly correlated with the presence or absence of neurofibrillary tangles.

Aged↗
PubMed1998

Decreased trkA neurotrophin receptor expression in the parietal cortex of patients with Alzheimer's disease.

The cholinergic neurons of the basal forebrain system are sensitive to nerve growth factor (NGF), a member of the neurotrophin gene family. Since the cholinergic system is affected early in the course of Alzheimer's disease (AD), it was hypothesized that a deficit in NGF, e.g. reduced neurotrophin uptake by specific receptors, may play a role in neuronal cell death in AD. We quantitated mRNA levels of neurotrophins (NGF, BDNF, NT-3, NT-4/5) and their receptors (trkA, trkB, trkC, p75) in AD postmortem parietal cortex (n = 16) and cerebellum (n = 11). We applied highly sensitive reverse transcription-polymerase chain reaction (RT-PCR) in rapid autopsy derived brain tissue (mean postmortem delay 147+/-96 min., n = 53) to minimize postmortem mRNA variations. In the AD parietal cortex trkA mRNA levels were more than two times lower as compared to controls (n = 16, mean+/-SEM 0.26+/-0.07 units/S12, range, 0-1.78, and n = 11, 0.59+/-0.10 units/S12, range, 0.17-1.10, respectively, P = 0.015). TrkA mRNA levels did not appear to be altered in the AD cerebellum as compared to normal human cerebellum. NGF, BDNF, NT-3, NT-4/5, as well as trkB, trkC and p75 mRNA levels were unchanged in AD parietal cortex and cerebellum as compared to controls. This finding suggests that a reduced expression of the trkA receptor may contribute to impaired NGF-trkA signalling and a reduced transport of NGF in cholinergic neurons. These results reveal a central specific role of the high affinity NGF receptor during neurodegeneration in AD.

Aged↗
PubMed1998

Increased blood mercury levels in patients with Alzheimer's disease.

Alzheimer's disease (AD) is a common neurodegenerative disorder that leads to dementia and death. In addition to several genetic parameters, various environmental factors may influence the risk of getting AD. In order to test whether blood levels of the heavy metal mercury are increased in AD, we measured blood mercury concentrations in AD patients (n = 33), and compared them to age-matched control patients with major depression (MD) (n = 45), as well as to an additional control group of patients with various non-psychiatric disorders (n = 65). Blood mercury levels were more than two-fold higher in AD patients as compared to both control groups (p = 0.0005, and p = 0.0000, respectively). In early onset AD patients (n = 13), blood mercury levels were almost three-fold higher as compared to controls (p = 0.0002, and p = 0.0000, respectively). These increases were unrelated to the patients' dental status. Linear regression analysis of blood mercury concentrations and CSF levels of amyloid beta-peptide (A beta) revealed a significant correlation of these measures in AD patients (n = 15, r = 0.7440, p = 0.0015, Pearson type of correlation). These results demonstrate elevated blood levels of mercury in AD, and they suggest that this increase of mercury levels is associated with high CSF levels of A beta, whereas tau levels were unrelated. Possible explanations of increased blood mercury levels in AD include yet unidentified environmental sources or release from brain tissue with the advance in neuronal death.

Aged↗
PubMed1998

Predictors of relapse and rehospitalization in schizophrenia and schizoaffective disorder.

In a German multicenter treatment study, 354 patients with schizophrenia and schizoaffective disorder were followed for 2 years. The data collected were taken as a basis for the present predictor study. For the first time, the technique of classification and regression tree (CART) analysis has been employed for this purpose. CART yielded informative data and appeared to be a useful instrument in predictor research. On the outcome variables "relapse" and "rehospitalization," significant predictor variables were found in several areas: neuroleptic treatment, onset and previous course (precipitating factors, first manifestation, hospitalization in the preceding year, suicide attempts), psychopathology (residual type, schizoaffective disorder), social adjustment (marital status, employment, intensity of life, Phillips score), previous life experiences (traumatic experiences and psychiatric or developmental disturbances in childhood), and biology (gender, age). Our investigation confirmed the generally prevalent views regarding the value of neuroleptic treatment, the multifactorial etiology, and the vulnerability stress model of schizophrenia.

Adult↗
PubMed1998

Cerebrospinal fluid levels of amyloid precursor protein and amyloid beta-peptide in Alzheimer's disease and major depression - inverse correlation with dementia severity.

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive dementia that ultimately leads to death. Histopathological hallmarks of AD include brain amyloid deposits and neurofibrillary tangles. Major depression is a frequent diagnosis in every gerontopsychiatric clinic that sees patients with both cognitive and affective disorders. Many depressed patients, in fact, are clinically characterized by cognitive impairments. Thus, an assay that excludes - or confirms - probable AD in cognitively impaired patients is desirable. Such assays may use protein markers that are derived from such histopathologically relevant molecules as the amyloid precursor protein (APP) and its derivatives including the amyloid beta-peptides (Abeta). To evaluate the differential diagnostic properties of cerebrospinal fluid (CSF) Abeta and secreted soluble ectodomain (APPs), we quantitated CSF levels of these measures in AD patients and compared them to age-matched control patients with major depression. CSF levels of APPs and Abeta were similar in patients with AD or major depression, and the apolipoprotein E genotype had no influence on CSF levels of Abeta in AD patients. Measurement of Abeta peptide using a novel zinc/copper capture ELISA that detects aggregated Abeta peptides as well demonstrated similar levels in AD and major depression. In AD patients, CSF levels of total Abeta (Abeta1-40 plus Abeta1-42) were inversely correlated with a functional measure of dementia severity (NOSGER), suggesting that CSF levels of Abeta decrease with advancing severity of AD. Thus, CSF levels of Abeta are not useful for the differentiation of AD from major depression. However, CSF levels of Abeta reflect the severity of dementia and may be useful as biological markers of the stage of the disease.

Aged↗