Clinically relevant glioblastoma patient-derived xenograft models to guide drug development and identify molecular signatures.

Glioblastoma (GBM) heterogeneity, aggressiveness and infiltrative growth drastically limit success of current standard of care drugs and efficacy of various new therapeutic approaches. There is a need for new therapies and models reflecting the complex biology of these tumors to analyze the molecular mechanisms of tumor formation and resistance, as well as to identify new therapeutic targets. We established and screened a panel of 26 patient-derived subcutaneous (s.

Treatment with 5-azacitidine delay growth of glioblastoma xenografts: a potential new treatment approach for glioblastomas.

Purpose: Glioblastoma multiforme (GBM) is the most lethal primary brain tumor in adults. The epigenetically active ribonucleoside analog 5-azacitidine is a new therapy option that changes tumor cell chromatin, which is frequently modified by methylation and deacetylation in malignant gliomas.

Methods: In vitro, we analyzed cell viability, cell apoptosis, and migration of human GBM cells.

Conversion to dementia in mild cognitive impairment is associated with decline of N-actylaspartate and creatine as revealed by magnetic resonance spectroscopy.

The purpose of the present study was to longitudinally track changes of metabolite markers detectable by magnetic resonance spectroscopy (MRS) in subjects with mild cognitive impairment (MCI) and to analyze these changes with respect to the rate of cognitive decline and clinical disease progression. Fifteen subjects with MCI and 12 healthy elderly controls were investigated longitudinally (average follow-up period: 3.4 years) using absolute quantification of metabolites within the mid-parietal grey matter and the parietal white matter [N-acetylaspartate (NAA), myo-inositol, choline, creatine, glutamine)] Our main findings include that a longitudinal decline in cognitive function (particularly in memory function) within the MCI group was predicted by a decline in absolute concentrations of the metabolic markers NAA and creatine.

Apolipoprotein E epsilon 4 is associated with an increased vulnerability to cell death in Alzheimer's disease.

The presumption to suffer from Alzheimer's disease (AD) accelerates with aging. One important risk factor seems to be the isoform epsilon 4 of the apolipoprotein E gene (Apo epsilon 4), which increases the risk to develop AD at an earlier age. Furthermore, convincing evidence is provided that apoptotic cell death mechanisms play an important role in neuronal cell death in AD.

Enhanced ROS-generation in lymphocytes from Alzheimer's patients.

Introduction: Reactive oxygen species (ROS) have been implicated in neurodegeneration and seem to be involved in the physiology and pathophysiology of several diseases, including normal aging and Alzheimer's disease (AD). Enhanced ROS production in aging or AD is not restricted to the brain, but can also been seen in several peripheral tissues. The objective of the present study was to evaluate whether the mechanisms involved in the generation of oxidative stress in normal senescence and Alzheimer's disease are identical or not.

[The health policy of the "Council of the People's Representatives": the German revolution 1918/1919 in medical historical perspective II: health policy as a factor of continuity and stability].

Most important for the events at the turn of 1918/19 was the coincidence of the revolution and the end of the war. This meant that in a very short time the troops had to be withdrawn from the front, the size of the army had to be reduced, and the wartime economy had to be transformed into a peace economy. Apart from the resulting economical and social problems, military demobilisation was closely linked with medical and health political difficulties.

Longitudinal study on the relationship between symptomatology of dementia and levels of subjective burden and depression among family caregivers in memory clinic patients.

The objective was to evaluate the course and severity of dementia-related symptoms and their relationship to caregivers' subjective burden and depression over time. Forty-five patients with dementia and their caregivers were followed over a period of 2 years. Patients' cognition, function, and behavioral/psychological symptoms were assessed by the Mini Mental State Examination, Syndrome Kurz Test, Geriatric Depression Screening scale, Instrumental Activities of Daily Living Scale, Physical Self Maintenance Scale, Behavioral Abnormalities in Alzheimer's Disease Rating Scale, and Nurses Observation Scale for Geriatric Patients.

[The health policy of the "Rat der Volksbeauftragten": the German revolution of 1918/19 in medical historical perspective--part I: Legislation on health policy].

After the fall of the monarchy and the proclamation of the republic on 9 November 1918, the "Rat der Volksbeauftragten" ("Council of People's Representatives") was established as a provisional revolutionary government. It consisted of three members of the Majority Social Democratic Party (MSDP) and three members of the Independent Social Democratic Party (USPD). Because of irreconcilable political-ideological differences, the members of the USPD left government on 28 December, so that from this time until 10 February 1919 the MSPD governed alone.

Subclinical hyperthyroidism in dementia and correlation of the metabolic index in FDG-PET.

Aim: Thyroid hormone status and thyroid antibodies were evaluated in patients suffering from dementia for further study of an association of hyperthyroidism with AD and vascular dementia (VD), respectively.

Patients: In 77 patients with dementia, and 42 controls, thyrotropin (TSH) and thyroid antibodies were correlated with the different types of dementia and the metabolic index (MI) based on imaging with F-18-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET).

Results: Twenty-two of all patients with dementia (29%) had borderline (TSH 0.

No effects of a combination of caregivers support group and memory training/music therapy in dementia patients from a memory clinic population.

Objectives: To evaluate the impact of a combination of caregiver support group and memory training/music therapy in dementia patients on behavioural and psychological symptoms (BPSD) and caregiver burden compared to a control group.

Method: Eighteen patient-carer-dyads in the treatment group and 18 patient-carer-dyads as controls were studied in the setting of a memory clinic of a psychiatric university hospital over a period of 2 years. Controls were matched for age, gender, diagnosis, dementia severity, living arrangement and medication.

Impact of aging: sporadic, and genetic risk factors on vulnerability to apoptosis in Alzheimer's disease.

The identification of specific genetic (presenilin-1 [PS1] and amyloid precursor protein [APP] mutations) and environmental factors responsible for Alzheimer's disease (AD) has revealed evidence for a shared pathway of neuronal death. Moreover, AD-specific cell defects may be observed in many other nonneuronal cells (e.g.

Olfactory function in mild cognitive impairment and Alzheimer's disease: an investigation using psychophysical and electrophysiological techniques.

Objective: To clarify the olfactory deficit hypothesis regarding Alzheimer's disease, the authors compared olfactory function in patients with Alzheimer's disease, subjects with mild cognitive impairment, and healthy comparison subjects.

Method: Olfactory function of 14 patients with mild Alzheimer's disease, eight subjects with mild cognitive impairment, and eight healthy age-matched comparison subjects was assessed with both psychophysical tests and olfactory event-related potentials.

Results: Group comparison of the psychophysical test results showed a significant main effect of diagnosis for odor detection threshold, odor discrimination, and odor identification.

[Etiology and pathogenesis of Alzheimer dementia].

Alzheimer's disease (AD) is the most common cause of primary dementia, characterized by a progressive process of pathophysiological restructuring of the brain over decades. The hallmark of Alzheimer's disease is the extracellular accumulation and deposition of insoluble amyloid, to be found in the parenchyma in the form of amyloid plaques and in meningeal and cerebral vessels as a congophile angiopathy. Equally conspicuous is the intraneuronal occurrence of neurofibrillary tangles, consisting mainly of hyperphosphorylated tau-protein.

Psychometric properties of Clock Drawing Test and MMSE or Short Performance Test (SKT) in dementia screening in a memory clinic population.

Objective: To evaluate five different scoring methods of the Clock Drawing Test (CDT) and to examine whether a combination of Mini Mental State Examination (MMSE) or Short Performance Test (Syndrom Kurz Test, SKT), respectively, with CDT can be used for cognitive screening.

Methods: Retrospective blinded analysis of clock drawing performance using five scoring methods (Shulman et al. (1986), Sunderland et al.

[Therapy of Alzheimer dementia. Current status and prospects].

In recent years, considerable progress has been made both in the diagnosis and treatment of dementia. Drugs have been developed which enhance cognitive performance in a large percentage of those afflicted, delay impairment of the ability to cope with the tasks of daily life, and avoid premature admission to a nursing home. In the practical medical care setting, however, these advantages are being utilized to only a limited extent, and this despite the fact that numerous therapeutic options are now available for the treatment of AD.

No short-term effects of high-frequency electromagnetic fields on the mammalian pineal gland.

There is ample experimental evidence that changes of earth-strength static magnetic fields, pulsed magnetic fields, or alternating electric fields (60 Hz) depress the nocturnally enhanced melatonin synthesis of the pineal gland of certain mammals. No data on the effects of high-frequency electromagnetic fields on melatonin synthesis is available. In the present study, exposure to 900 MHz electromagnetic fields [0.