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Biomedical subjects

J Kornhuber

Publications and source records attributed to J Kornhuber.

At least 19 recordsLinked to original sources
PubMed2006

Memantine fails to facilitate partial cigarette deprivation in smokers--no role of Memantine in the treatment of nicotine dependency?

The efficacy of Memantine in the treatment of nicotine dependency in humans remained to be evaluated. The aims of our pilot study were to investigate (1) the effectiveness of Memantine in facilitating smoking reduction and (2) the influence of Memantine on the perception of nicotine. In order to achieve these aims we conducted a placebo controlled double-blind parallel group study in smokers (n = 20 per group). Before the beginning of the treatment-phase (10/20 mg Memantine per day) all participants were instructed to reduce smoking (partial deprivation). Before and during partial deprivation we registered the daily cigarette consumption and craving estimates. Following nasal stimulation with nicotine enantiomers hedonic and intensity estimates and the discrimination ability were assessed. Memantine failed to facilitate smoking reduction and did not influence the perception of nicotine with the exception of a weak reduction of olfactory intensity estimates reaching statistical significance for one nicotine enantiomer only.

Adult↗
PubMed2006

Decreased circulating CD34+ stem cells in early Alzheimer's disease: Evidence for a deficient hematopoietic brain support?

Hematopoietic stem cells contribute to mammalian brain tissue regeneration by transdifferentiation processes. We found decreased counts of circulating CD34+ cells in early Alzheimer's dementia (AD; P = 0.01), which significantly correlated with age (r = -0.661; P = 0.001), cerebrospinal fluid beta-amyloid (Abeta)1-42 (r = -0.467; P = 0.025) and most pronounced the Abeta42/40 ratio (r = -0.688; P = 0.005). Our data suggest a deficient regenerative hematopoietic support for the central nervous system in early AD.

Alzheimer Disease↗
PubMed2006

[Neurobiological mechanisms and pharmacological treatment options for alcohol craving].

In the last years, numerous studies have been performed on neurobiological mechanisms in alcohol craving. Changes in the hypothalamic cortisol pathway and the leptin metabolism, which is also associated with pharmacological interventions, have been of special interest. With acamprosate and naltrexone two substances exist for pharmacotherapy, but recent results about the efficacy are controversial. The clinical profit of disulfiram has been shown, at least in a subgroup of patients. Besides, there are several promising candidate substances. Current investigations focus on a differentiated pharmacotherapy of alcohol dependence, including psychological and genetic factors.

Acamprosate↗
PubMed2006

Homocysteine levels in aqueous humor and plasma of patients with primary open-angle glaucoma.

We determined homocysteine (Hcy) levels in aqueous humor (AH) and plasma and their association with B-vitamin levels in patients with primary open-angle glaucoma (POAG) and controls. Both AH Hcy and plasma Hcy levels were significantly increased in POAG, and elevation of AH Hcy and plasma Hcy was a significant risk factor for POAG. In contrast to controls, neither plasma nor AH Hcy of POAG patients demonstrated a significant association with important non-genetic determinants of elevated Hcy such as low B-vitamin levels, increasing age and caffeine consumption. Considering that Hcy is a neurotoxin that induces apoptotic retinal ganglion cell death via stimulation of the N-methyl-D-asparate (NMDA) receptor, increased Hcy concentrations in AH and plasma might contribute to the optic nerve damage in POAG.

Aged↗
PubMed2006

CSF diagnosis of Alzheimer's disease and dementia with Lewy bodies.

Differential diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) is often crucial. CSF Tau protein and Amyloid-beta (A beta) peptides have shown diagnostic value for the diagnosis of AD, but discrimination from DLB was poor.Herein, we investigate CSF of 18 patients with probable AD, 25 with probable DLB and 14 non-demented disease controls (NDC) by A beta-SDS-PAGE/immunoblot and commercially available ELISAs for A beta1-42 and tau. CSF A beta peptide patterns and tau exhibited disease specific alterations among AD and DLB. The ratio of A beta1-42 to A beta1-38 and A beta1-42 to A beta1-37, respectively, in combination with absolute tau, yielded a sensitivity and specificity of 100 and 92%, respectively. We conclude that CSF A beta peptide patterns and tau levels reflect disease-specific pathophysiological pathways of these dementias as distinct neurochemical phenotypes. Combined evaluation of these biomarkers provides a reasonable accuracy for differential diagnosis of AD and DLB.

Aged↗
PubMed2006

Biological markers to predict previous alcohol withdrawal seizures: a risk assessment.

Recent studies have shown that both, elevated homocysteine and prolactin plasma levels are associated with a higher risk of alcohol withdrawal seizures. The aim of this study was to evaluate the predictive qualities of a combined assessment of homocysteine and prolactin for previous alcohol withdrawal seizures. Therefore, 117 male patients suffering from alcohol dependency were included into the study. Homocysteine was measured directly at admission, prolactin the morning following admission for detoxification treatment. Pearson's chi(2)-test showed significant results for the combined assessment of both parameters (chi(2) = 14.71, p = 0.001). Multivariate logistic regression also revealed significant predictive qualities (p = 0.001, OR = 9.23, 95%CI = 2.36-36.05). A combination of both, homocysteine and prolactin, may help to assess the individual risk of alcohol withdrawal seizures in clinical practice.

Adult↗
PubMed2006

The German Competence Net Dementias: standard operating procedures for the neurochemical dementia diagnostics.

Aging of population results in an increasing number of patients with dementia. Therefore, recently a BMBF-supported project, Competence Net Dementia, was launched to reveal diagnostic, therapeutic, and epidemiologic aspects of demential disorders. In this project, our task was to establish and maintain human body fluids (HBF) bank to collect cerebrospinal fluid, plasma, serum, and full blood of patients enrolled into the study. As the pre-analytical sample handling is a prerequisite of all studies aiming at finding novel disease biomarkers, standard operating procedures (SOPs) were launched by our group to allow standardized collection, storage, and shipment of the samples among all 14 University centers involved in HBF collection. Currently, to our best knowledge the CND HBF bank represents one of the largest prospectively collected set of the samples from subjects with mild cognitive impairment and early dementias. With the samples collected in the HBF bank, recently introduced analytical technologies (like e.g. surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), differential gel electrophoresis (DIGE), and multiplexing) can be promptly tested with regard to their potential usefulness in neurochemical dementia diagnostics.

Brain Chemistry↗
PubMed2006

Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism.

DNA methyltransferases (DNMTs) are involved within the epigenetic control of DNA methylation processes. Recently, it has been shown that the genomic DNA methylation in patients with alcoholism is increased. In the present controlled study we observed a significant decrease of mRNA expression of DNMT-3a and DNMT-3b when comparing alcoholic patients (n = 59) with healthy controls (n = 66): DNMT-3a (t = -2.38, p = 0.019), DNMT-3b (t = -2.65, p = 0.008). No significant differences were seen for DNMT-1 and Mbd-2 (Methyl-CpG-Binding-Domain protein 2) expression. Additionally, we observed a significant negative correlation between DNMT-3b expression and the blood alcohol concentration (r = -0.45, p = 0.003) which might explain the decrease of DNMT-3b mRNA expression in alcoholic patients. Using a multivariate model we observed that the increase (10%) of genomic DNA methylation in patients with alcoholism was significantly associated with their lowered DNMT-3b mRNA expression (multiple linear regression, p = 0.014). Since methylation of DNA is an important epigenetic factor in regulation of gene expression these findings may have important implications for a possible subsequent derangement of epigenetic control in these patients.

Adult↗
PubMed2006

[Fritz Flügel (1897-1973). Early research on neuroleptics].

In the early 1950s, Fritz Flügel and his colleagues at the Neurology Clinic of the University of Erlangen in Germany contributed greatly to the clinical introduction of chlorpromazine in German psychiatry. Flügel's clinical work made possible in exemplary fashion the first German psychiatric research on neuroleptics. Between 1953 and 1963, scientists were trying to find a theoretical explanation for the positive psychic effect which had become evident during empirical tests with the new substance. Within a few years, the new drug had its breakthrough, which simply was based on worldwide therapeutical success and good empirical results. That already had happened about 10 years before Carlsson came up with the first plausible theory of neuroleptic function by formulating the dopamine hypothesis in 1963. This brought new energy and developments in psychiatric research in general. Newly developed theses have thoroughly changed the therapeutic approach in psychiatry and the way in which pathophysiological contexts of the brain are understood.

Antipsychotic Agents↗
PubMed2006

Cotrimoxazole-induced psychosis: a case report and review of literature.

We present a case of acute psychosis in a 46-year-old woman who had been treated orally with cotrimoxazole because of a severe infection of the urinary tract. She had started to develop psychotic symptoms with bizarre behavior two days before admission. Following discontinuation of antibiotic therapy, including cessation of treatment with cotrimoxazole and the induction of antipsychotic treatment, her mental state resolved to a stable premorbid level within 36 hours.

Anti-Infective Agents, Urinary↗
PubMed2005

Region specific distribution of levomepromazine in the human brain.

OBJECTIVE: The aim of this study was to examine concentrations of levomepromazine and its metabolite desmethyl-levomepromazine in different regions of human brain and in relationship to drug-free time. METHODS: Drug concentrations were measured in up to 43 regions of 5 postmortem human brains of patients previously treated with levomepromazine. To enable statistical comparison across brain regions several smaller brain areas were put together to form larger brain areas (cortex cerebri, limbic system, cerebellum, basal ganglia, thalamus). Mean values of drug concentrations in these larger brain areas were used in a repeated measurement ANOVA to analyze for region specific distribution. The elimination half-life in brain tissue was estimated with a NONMEM population kinetic analysis using the mean value of all brain regions of an individual case. RESULTS: Levomepromazine and desmethyl-levomepromazine appear to accumulate in human brain tissue relative to blood. Mean concentrations differed largely between individual brains, in part due to differences in dose of drug, duration of treatment and drug-free time before death. There was an apparent region-specific difference in levomepromazine concentrations with highest values in the basal ganglia (mean 316 ng/g) and lowest values in the cortex cerebri (mean 209 ng/g). The elimination half-life from brain tissue is longer than from blood and was calculated to be about one week. Similar results were obtained with desmethyl-levomepromazine. CONCLUSIONS: Levomepromazine shows a region-specific distribution in the human brain with highest values in the basal ganglia. This might be the consequence of low expression of the metabolic enzyme Cyp2D6 in the basal ganglia. If this finding is true also for other neuroleptic drugs it might increase our understanding of preferential toxicity of neuroleptic drugs against basal ganglia structures and higher volumes of basal ganglia of neuroleptic-treated patients. Furthermore, patients exposed to levomepromazine cannot be considered to be free of residual effects of the drug for a number of weeks after withdrawal.

Aged↗
PubMed2005

Short-term cognition deficits during early alcohol withdrawal are associated with elevated plasma homocysteine levels in patients with alcoholism.

Higher plasma homocysteine levels have been found in actively drinking alcoholics as well as in early abstinent patients. Furthermore, elevated homocysteine levels are associated with cognitive decline in dementia and in healthy elderly people. The aim of this prospective study was to investigate a possible association between homocysteine serum levels and clinically well known cognitive deficits during alcohol withdrawal. We examined 89 patients (67 men, 22 women) during early withdrawal treatment. Cognitive function was assessed using the c.I.-Test. Patients with cognitive deficits showed significantly higher homocysteine serum levels (Mann-Whitney-U, p=0.004) than patients without cognitive deficits, while the difference in blood alcohol concentration was not significant. Using logistic regression analysis, cognitive deficits were best predicted by high homocysteine serum levels (Wald chi2=4.071, OR=1.043, 95% CI 1.001-1.086, p<0.05), which was confirmed by Receiver Operating Curves (AUC=0.68, 95% CI=0.57-0.79, p=0.004). The present results show first evidence of an association between elevated plasma homocysteine levels in alcoholics and cognition deficits in patients undergoing alcohol withdrawal.

Adult↗
PubMed2005

Evaluation of oxidative stress measurements in obstructive sleep apnea syndrome.

Assessment of reactive oxygen species (ROS) is highly important in neurodegenerative disorders and neuroleptic treatment. However, conflicting results have been reported, which may arise from methodological difficulties. Obstructive sleep apnea (OSA) syndrome with episodic hypoxia-reoxygenation is proposed as a human model for the investigation of ROS measurements. Despite a broad analytical approach comprising lipid peroxidation and amino acid oxidation products, oxidative DNA damage, and activity of the antioxidant defense, only plasma malondialdehyde (MDA) and urinary o,o'-dityrosine seemed to be appropriate, robust biomarkers of oxidative stress, which are also simple enough for routine clinical use. MDA concentrations correlated with a duration of nocturnal desaturation below 85% (r = 0.77, p<0.0005), and o,o'-dityrosine levels decreased after therapy (p<0.05) as a function of baseline concentrations (r = -0.61, p<0.05). Gender effects in ROS generation also have to be considered. At present, we recommend the application of several oxidative stress measurements at different time points, preferably involving plasma MDA and urinary o,o'-dityrosine.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2005

Joint analysis of the NACP-REP1 marker within the alpha synuclein gene concludes association with alcohol dependence.

Various studies have linked alcohol dependence phenotypes to chromosome 4. One candidate gene is NACP (non-amyloid component of plaques), coding for alpha synuclein. Recently, it has been shown that alpha synuclein mRNA is increased in alcohol-dependent patients within withdrawal state. This increase is significantly associated with craving, especially obsessive craving. On the basis of these observations, the present study analysed two polymorphic repeats within the NACP gene. We found highly significant longer alleles of NACP-REP1 in alcohol-dependent patients compared with healthy controls (Kruskal-Wallis test, chi(2)=99.5; df=3, P<0.001). In addition, these lengths significantly correlate with levels of expressed alpha synuclein mRNA (chi(2)=8.83; df=2, P=0.012). The present results point to a novel approach for a genetic determination of craving, a key factor in the genesis and maintenance not only of alcoholism but also of addiction in general.

Adult↗
PubMed2005

Homocysteine plasma levels are elevated in females with anorexia nervosa.

In the present pilot study significantly (T = 2.46, P = 0.018) higher levels of homocysteine were found in female anorectic patients (14.07, SD 7.3 micromol/l; n = 18) when compared with bulimic patients (10.25, SD 2.82; n = 27) or healthy controls (8.10, SD 1.79; n = 25). Since homocysteine can induce neuronal cell death leading to brain atrophy in different diseases and since it has been linked to depressive disorders these findings may have important implications for understanding common symptoms in patients suffering from anorexia.

Adolescent↗
PubMed2005

High activity of acid sphingomyelinase in major depression.

Acid sphingomyelinase (A-SMase) and its reaction product ceramide may play a role in the pathophysiology of depressive disorders and in the therapeutic action of antidepressive drugs. In a prospective case-control study, A-SMase activity was measured in peripheral blood mononuclear cells of 17 patients with a major depressive episode who were free of antidepressant drug therapy for at least 10 days and 8 healthy volunteers. In the patient group, A-SMase activity was correlated to the score (n=17, r=0.64, P=0.005). The patient group exhibited higher A-SMase activity compared to healthy volunteers (T=2.09, df=21.33, P<0.05). In addition, we demonstrate that the antidepressants imipramine and amitriptyline induce a long-term reduction of the activity of A-SMase in cultured cells.

Adult↗
PubMed2005

Cognitive impairment and its association with homocysteine plasma levels in females with eating disorders - findings from the HEaD-study.

Higher plasma homocysteine levels have been found in females with anorexia nervosa. Furthermore, elevated homocysteine levels are associated with cognitive decline in dementia and healthy elderly people. Aim of this prospective study was to investigate a possible association between homocysteine serum levels and Clinically well known cognitive deficits in females with eating disorders. We found that moderately elevated plasma homocysteine levels were associated with normal short- and long-term verbal memory while normal plasma homocysteine levels were associated with poorer memory performance in 14 females with anorexia nervosa and 12 females with bulimia nervosa (logistic forward regression Wald chi(2)=8.566, OR=24.75, CI 2.89 - 212.23, P=0.003). These results indicate that under the special circumstances of eating disorders elevated homocysteine levels improve memory signaling possibly by facilitating long-term potentiation.

Adolescent↗