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M Rösler

Publications and source records attributed to M Rösler.

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

[Significance of personality markers in Alzheimer dementia].

Personality traits are of raising importance in the investigation of the causes of Alzheimer's disease. The examination of possible correlations between personality traits and the presence of dementia is complicated by some methodical problems concerning the objective, reliable, and valid assessment especially of premorbid personality style of demented persons. There is some evidence that a higher level of education can not be considered as protective factors but seems to delay the progression and modify the clinical manifestation of the disease. How other premorbid personality traits influence the course of the disease is still unresolved. A trend towards an uniform personality alteration in the course of the disease seems to exist. Especially when selecting non-pharmacological therapeutical or training strategies or even in the interaction with the patients, it seems to be important to take personality change into consideration.

Aged↗
PubMed2000

[The role of diffuse axonal injury in psychiatric assessment of brain-head trauma].

The concept of diffuse axonal injury is presented and the relevance in medicolegal assessment of brain injured patients is discussed. The lesion pattern of diffuse axonal injury not only plays a significant role in the acute management and rehabilitation of brain injured patients but also in issues of litigation. Brain imaging techniques are most important in the evaluation of structural damage to the brain and play a pivotal role in the detection of diffuse axonal injury. While computer-tomography follow-up studies may be valuable for the detection of diffuse axonal injury, magnetic resonance imaging is superior due to better sensitivity and contrast-resolution. The article presents selected case studies and illustrates the different lesion patterns.

Axons↗
PubMed1999

Polymorphisms of the human apolipoprotein E promoter and bleomycin hydrolase gene: risk factors for Alzheimer's dementia?

In addition to the apolipoprotein E (ApoE) tri-allele polymorphism, genetic variants of the apolipoprotein E promoter (-491A/T) and the bleomycin hydrolase (BH-PEN) gene have also been proposed as genetic risk factors for Alzheimer's dementia (AD). Since reports about the relevance of these polymorphisms for the pathogenesis of AD have been contradictory, we performed an association study with some modifications. First, the control group in this study was made up of non-demented psychiatric inpatients, rather than healthy subjects. This procedure allows the specificity of the relationship between a given genotype and AD (as opposed to other psychiatric disorders) to be determined. Second, as an alternative to preexisting relatively time consuming techniques, BH-PEN polymorphism was determined using a simplified method based on PCR genotyping. We found a significant linkage disequilibrium between the -491A/T and ApoE polymorphisms. However, no direct association was observed between the -491A/T or BH-PEN polymorphism and AD.

Alleles↗
PubMed1999

Impaired phosphorylation of cyclic AMP response element binding protein in the hippocampus of dementia of the Alzheimer type.

Cyclic AMP (cAMP) is disrupted in the brain in dementia of the Alzheimer type (DAT). We investigated whether the cAMP reduction is accompanied by an alteration in the cAMP response element binding protein (CREB) downstream in DAT and control hippocampi. Immunoreactivity of pCREB was significantly decreased in DAT, while total CREB level was unchanged. These findings indicate that impaired cAMP signaling may contribute to the pathophysiology of the disease.

Adult↗
PubMed1999

Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial.

OBJECTIVES: To assess the effects of rivastigmine on the core domains of Alzheimer's disease. DESIGN: Prospective, randomised, multicentre, double blind, placebo controlled, parallel group trial. Patients received either placebo, 1-4 mg/day (lower dose) rivastigmine, or 6-12 mg/day (higher dose) rivastigmine. Doses were increased in one of two fixed dose ranges (1-4 mg/day or 6-12 mg/day) over the first 12 weeks with a subsequent assessment period of 14 weeks. SETTING: 45 centres in Europe and North America. PARTICIPANTS: 725 patients with mild to moderately severe probable Alzheimer's disease diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, and the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. OUTCOME MEASURES: Cognitive subscale of the Alzheimer's disease assessment scale, rating on the clinician interview based impression of change incorporating caregiver information scale, and the progressive deterioration scale. RESULTS: At the end of the study cognitive function had deteriorated among those in the placebo group. Scores on the Alzheimer's disease assessment scale improved in patients in the higher dose group when compared with patients taking placebo (P<0.05). Significantly more patients in the higher dose group had improved by 4 points or more than had improved in the placebo group (24% (57/242) v 16% (39/238)). Global function as rated by the clinician interview scale had significantly improved among those in the higher dose group compared with those taking placebo (P<0.001), and significantly more patients in the higher dose group showed improvement than did in the placebo group (37% (80/219) v 20% (46/230)). Mean scores on the progressive deterioration scale improved from baseline in patients in the higher dose group but fell in the placebo group. Adverse events were predominantly gastrointestinal, of mild to moderate severity, transient, and occurred mainly during escalation of the dose. 23% (55/242) of those in the higher dose group, 7% (18/242) of those in the lower dose group, and 7% (16/239) of those in the placebo group discontinued treatment because of adverse events. CONCLUSIONS: Rivastigmine is well tolerated and effective. It improves cognition, participation in activities of daily living, and global evaluation ratings in patients with mild to moderately severe Alzheimer's disease. This is the first treatment to show compelling evidence of efficacy in a predominantly European population.

Activities of Daily Living↗
PubMed1999

[Assessment of the attention-deficit hyperactivity disorder in adults].

The attention-deficit hyperactivity disorder (ADHD) is one of the most common disorders in childhood and adolescence with a prevalence of app. 5%. The importance of ADHD in childhood as a factor of vulnerability for psychiatric disorders in adults is becoming a focus of discussion. It was shown that there is a comorbidity in adults with substance abuse, delinquency and personality disorders. There is a growing evidence that ADHD will persist in a significant number of patients during adulthood. This is the first german study to evaluate this interdependence. We examined 164 adult inpatients and 48 healthy volunteers with the Wender Utah Rating Scale (WURS), a retrospective self-evaluation scale for the diagnosis of ADHD in childhood, and the Eysenck impulsiveness questionnaire I7. It could be shown that the WURS and the I7 are suitable instruments for the evaluation of the ADHD in adults especially concerning the aspects of attention deficits and impulsiveness.

Adult↗
PubMed1998

Free radicals in Alzheimer's dementia: currently available therapeutic strategies.

Substantial evidence now exists that oxidative stress may play an important role in the etiopathogenesis of DAT. The different sources of oxidative stress in DAT are suggesting several pharmacological opportunities for influencing the disease. It is possible to distinguish 2 major types of possible therapeutic agents according to their pharmacological point of attack. 1. Radical scavengers, agents directly interacting with free radicals. Candidates of this type are gingko biloba, vitamins A, C, E and estrogen. 2. Antioxidants, which are able to prevent or decrease the production of free radicals by use of specific neuropharmacological properties. Candidates are selegiline, a MAO-B inhibitor well established in the therapy of Parkinson's disease, and tenilsetam, which is believed to be an AGE-inhibitor. Recent in vitro studies have demonstrated the efficacy of both types of therapeutic agents by preventing or delaying oxidative neural damage. Some clinical data exist regarding the antidementive properties particularly in terms of gingko biloba, selegiline and vitamin E. The efficacy studies about these compounds seem to indicate a promising future strategy in the therapy of DAT. But it is too early to draw definite conclusions since it is well known that all of our candidate substances do not act specifically as radical scavengers or antioxidants.

Alzheimer Disease↗
PubMed1998

Free radicals in Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disorder comprising multisystem atrophies probably caused by multifactorial processes. The disease is characterized by typical neuropathology, impaired synaptic function and massive cell loss. The pathobiochemistry of this disorder involves oxidative stress, which accumulates free radicals leading to excessive lipid peroxidation and neuronal degeneration in certain brain regions. Moreover, radical induced disturbances of DNA, proteins and lipid membranes have been measured. The hypothesis has been proposed that cellular events involving oxidative stress may be one basic pathway leading to neurodegeneration in Alzheimer's disease. In this work we report evidence for increased oxidative stress and disturbed defense mechanisms in Alzheimer's disease, which may result in a self-propagating cascade of neurodegenerative events. Furthermore it is evident from experimental data, that aggregation of beta-amyloid and beta-amyloid toxicity is favourably caused by oxidative stress. Therefore, oxidative stress plays a key role in the conversion of soluble to unsoluble beta-amyloid, suggesting that oxidative stress is primary to the beta-amyloid cascade.

Alzheimer Disease↗
PubMed1998

Non-fatal mirtazapine overdose.

We report the case of intoxication of a 41-year-old female patient suffering from major depression with mirtazapine complicated by severe hypothermia. The patient was brought to an intensive care unit 10 hours after intake of 1200 mg mirtazapine and 20 mg lorazepam and laying outside at outdoor temperatures below 0 degree C. The mirtazapine plasma-level was 368 ng/ml still after 41 hours. Body temperature was reduced to 26 degrees C and rhabdomyolysis due to hypothermia was observed. Cardial and respiratory function was compromised and intubation was necessary. The patient recovered without persisting somatic impairment.

Adult↗
PubMed1997

Oxidative-stress associated parameters (lactoferrin, superoxide dismutases) in serum of patients with Alzheimer's disease.

In this case/control study, serum levels of oxidative stress related parameters such as Fe-binding lactoferrin (LTF), Mn- and Zn,Cu-superoxide dismutase (SOD) were determined by enzyme linked immunoassays in patients suffering from the Alzheimer's dementia as well as in non-demented controls. The Mn-SOD concentration was significantly (P<0.05, U-test) reduced in patients suffering from Alzheimer's disease if compared to non-demented controls. The other parameters investigated did not differ significantly between both groups. Our findings give evidence for the hypothesis of a disturbed free radical metabolism in Alzheimer's disease. The specificity of these results remains to be clarified. Further studies are needed to elucidate the relevance of oxidative stress in the etiopathogenesis of the Alzheimer's disease.

Aged↗
PubMed1997

[Pharmacotherapy of Alzheimer dementia: therapy of cognitive symptoms--new results of clinical studies].

Recent investigations have given new insights into pathogenetical determinants of Alzheimer's disease. Amyloid deposition and neurofibrillary tangles are no longer considered to be primary pathological changes. Neurobiological research tries to work out the etiopathogenital cascade that finally causes Alzheimer's disease. So far, several relevant pathogenetical factors have been detected, e.g. pertubated control of glucose breakdown, impairment of oxidative metabolism, impaired neuroprotection due to increased oxidative stress and non-enzymatic protein glycation as well as immunological disturbances. Thus, new strategies for the development of cognition-enhancing drugs are emerging. The authors review reports on agents, that are under investigation for the treatment of cognitive symptomatology in Alzheimer's disease. Some of these agents have already been used for treatment of other medical conditions, e.g. nimodipine, memantine as well as selegiline. Many of them are still experimental. Promising strategies include antioxidative agents (e.g. vitamin E, vitamin C, beta-carotin), acetylcholinesterase-inhibitors with central selectivity (e.g. ENA 713), M1- and M4-muscarinic receptor agonists (milameline) as well as sabeluzole, a benzothazide derivative that shows neurotrophic activities and anti-inflammatory substances like indomethacin.

Aged↗
PubMed1997

[Clozapine in treatment of neuropsychiatric diseases in the elderly].

The atypical antipsychotic clozapine has been reported to be effective in otherwise refractory psychoses. This, and its low potential for inducing extrapyramidal side effects and tardive dyskinesia, predestines this drug for the treatment of psychotic disorders in late life. However, not much is known about the efficacy, safety and pharmacokinetics of clozapine in the treatment of aged patients. There are some studies and reports available about clozapine in the treatment of psychosis in patients suffering from dementia, schizophrenia and Parkinson's disease, which are reported here. They give some evidence that even low doses of clozapine are effective in controlling psychotic symptoms in the elderly. To avoid side effects, patient-specific factors and changes of pharmacokinetics in the elderly have to be considered. However, side effects including sedation, delirium, posturnal hypotension and the risk of agranulocytosis in particular limits the use of clozapine in elderly patients.

Aged↗
PubMed1996

The Gly/Glu polymorphism of the neurotrophin 3 gene: allele frequencies in a Caucasian population and relevance for psychiatric disorders.

Using a modified method for the determination of the genotype of the neurotrophin 3 Gly/Glu polymorphism by PCR, we investigated allele frequencies in patients suffering from different psychiatric diseases as well as in healthy controls. There was a much lower frequency of the allele Glu among Caucasians (0.006) than previously reported for a Japanese population (0.203). No homozygotes and only three heterozygotes for the rare allele could be detected: the latter belonged to the patient group and suffered from endogenous depression (two patients) and hebephrenia (one patient). Due to its very low frequency it seems unlikely that the allele Glu plays a decisive role in the aetiopathogenesis of schizophrenic psychoses or other psychiatric diseases. However, it cannot be excluded that it represents a risk or vulnerability factor.

Adult↗
PubMed1996

A null mutation allele in the CNTF gene and schizophrenic psychoses.

The maldevelopmental theory postulates disturbances in neural development as crucial factors in the aetiopathogenesis of schizophrenia. Neurotrophic factors, including ciliary neurotrophic factor (CNTF), play a central role in the regulation of such development. A mutation has been described for the CNTF gene, whereby subjects homozygous for the mutation lack CNTF. The polymerase chain reaction was used to amplify the CNTF gene region containing this mutation in whole blood genomic DNA. The mutation was detected by analysis of restriction fragment length polymorphisms. Patients suffering from schizophrenic psychosis (ICD-10 criteria) (51 from Würzburg, 83 from Barcelona), and healthy controls (62 from Würzburg, 50 from Barcelona) were investigated. In the Würzburg group, the frequency of subjects homozygous or heterozygous for the mutation was significantly higher among schizophrenic patients than in controls. However, no difference could be detected in the Spanish sample; the possible reasons for the different allele distribution in the two patient groups is discussed. It is concluded that the CNTF null mutation may be relevant to the aetiopathogenesis of schizophrenia in some patients, but further work is required to identify specifically the patient group for which it is important.

Adult↗
PubMed1996

Association between a null mutation in the human ciliary neurotrophic factor (CNTF) gene and increased incidence of psychiatric diseases?

We report a possible association between a null mutation in the human ciliary neurotrophic factor (CNTF) gene and psychiatric diseases. Prior findings that the mutant allele frequency is not significantly elevated in patients suffering from neurological diseases are confirmed. The frequency of the mutant allele was higher among psychiatric patients (0.192, n = 297) than among healthy controls and neurological patients (0.142, n = 267). This difference (one-tailed 2 x 2 chi-square test, P < 0.05) might be evidence that disturbances in the neurotrophic factor system could play a crucial role in the etiopathogenesis of psychiatric disorders, mainly psychoses.

Adult↗
PubMed1996

[New hypothesis on etiopathogenesis of Alzheimer syndrome. Advanced glycation end products (AGEs)].

Despite intense efforts, it has not yet been possible to clarify the etiopathogenesis of Alzheimer's dementia. There are, however, hypotheses which focus on certain aspects of this type of dementia, characterized by particular neuropathological alterations and clinical correlates. Recently, evidence has accumulated that advanced glycation endproducts (AGEs) could play an important role in the etiology of the Alzheimer's syndrome. AGEs are generated by an irreversible reaction through the non-enzymatic, long-term glycosylation of proteins. They are strongly resistant to proteolytic processes and induce protein crosslinking. They could thus inhibit the physiological functions of many proteins. Moreover, it is suggested that they contribute to the transformation of the soluble form of beta-amyloid into its unsoluble version. AGEs are also demonstrable in neurofibrillary tangles (NFTs). A further mechanism by which AGEs might be pathogenic is via their induction of oxidative stress. AGEs probably exert their pathological effects not only directly because of their chemical properties, but also by indirect receptor-mediated mechanisms. Further investigation of AGE-mediated mechanisms should reveal their role in the etiopathogenesis of the Alzheimer's syndrome and, finally, lead to the development of new pharmacological strategies aimed at inhibiting protein cross-linking.

Aged↗