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D Degner

Publications and source records attributed to D Degner.

At least 19 recordsLinked to original sources
PubMed2003

Hyperhomocysteinemia as a new risk factor for brain shrinkage in patients with alcoholism.

Chronic alcohol consumption can induce brain atrophy, whereby the exact mechanism of brain damage in alcoholics remains unknown. There is evidence that chronic alcoholism is associated with hyperhomocysteinemia. Homocysteine is an excitatory amino acid which markedly enhances the vulnerability of neuronal cells to excitotoxic and oxidative injury in vitro and in vivo. The present volumetric magnetic resonance imaging study included 52 chronic alcoholics and 30 non-drinking healthy controls. Patients were active drinkers and had an established diagnosis of alcohol dependence. We investigated the influence of different variables on the hippocampal volume of patients suffering from chronic alcoholism. We observed that pathological raised levels of plasma homocysteine showed the most significant correlation to hippocampal volume reduction (P<0.001, multiple regression analysis). Raised plasma levels of homocysteine are associated with hippocampal (brain) atrophy in alcoholism.

Adult↗
PubMed2003

Apolipoprotein E epsilon 4 is associated with hippocampal volume reduction in females with alcoholism.

There is evidence that a higher incidence of diverse neurodegenerative diseases is associated with the apolipoprotein E epsilon4 allele (ApoE4). Most recently it has been found that the ApoE4 allele is specifically related to an accelerated hippocampal atrophy in patients with Alzheimer's disease. Therefore, the aim of the present study was to investigate the association between ApoE4 genotypes and brain hippocampal volume reduction in alcoholics by using volumetric high-resolution MR imaging. In the present study, female alcoholics with the ApoE4 genotype were found to have significantly smaller hippocampal volumes than those not carrying an epsilon4 allele (ANOVA, p < 0.05), whereas no differences in hippocampal volume were seen in male alcoholics. Since hippocampal volume reduction is lately discussed to be proportional to brain atrophy, we propose that the alcohol-related brain atrophy in patients suffering from chronic alcoholism, is more pronounced in female carriers of the apoE epsilon4 allele. These findings indicate a genetic disposition for alcohol related brain atrophy in female carrying the ApoE4 genotype, which may also explain why female alcoholics are more susceptible to alcohol-induced brain damage.

Adult↗
PubMed2001

Risk assessment of alcohol withdrawal seizures with a Kohonen feature map.

Recently, it has been suggested that alcohol-induced hyperhomocysteinaemia in patients suffering from chronic alcoholism might be a risk factor for alcohol withdrawal seizures. In the present follow-up study 12 patients with chronic alcoholism who suffered from withdrawal seizures had significantly higher levels of homocysteine (Hcy) on admission (71.43 +/- 25.84 mol/l) than patients (n = 37) who did not develop seizures (32.60 +/- 24.87 mol/l; U = 37.50, p = 0.0003). Using a logistic regression analysis, withdrawal seizures were best predicted by a high Hcy level on admission (p < 0.01; odds ratio 2.07). Based on these findings we developed an artificial neural network system (Kohonen feature map, KFM) for an improved prediction of the risk of alcohol withdrawal seizures. Forty-nine patients with chronic alcoholism (12 with alcohol withdrawal seizures and 37 without seizures) were randomized into a training set and a test set. Best results for sensitivity of the KFM was 83.3% (five of six seizure patients were predicted correctly) with a specificity of 94.4% (one false positive prediction of 19 patients). We conclude that in patients with alcohol-induced hyperhomocysteinaemia the KFM is a useful tool to predict alcohol withdrawal seizures.

Adult↗
PubMed2000

[New antidepressant drugs. What side effects and interactions are to be expected?].

The new antidepressants, selective serotonin reuptake inhibitors (SSRI), selective serotonin noradrenalin reuptake inhibitors (SSNRI) and selective noradrenalin reuptake inhibitors (SNRI) have few clinically relevant side effects. Overall, the new antidepressants are better tolerated and cause fewer side effects than the classical tricyclic antidepressants (TCA). They have virtually no anticholinergic effects, a low level of toxicity, and produce no psychomotoric or cognitive impairment. Both the frequency and severity of gastrointestinal and CNS side effects, as well as tremor, are low. The results of the drug safety program (AMSP) confirm the good tolerability and low clinical side effects of these new substances.

Antidepressive Agents↗
PubMed2000

Oxidative stress and an altered methionine metabolism in alcoholism.

The exact mechanism of brain atrophy in patients with chronic alcoholism remains unknown. There is growing evidence that chronic alcoholism is associated with oxidative stress and with a derangement in sulphur amino acid metabolism (e.g. ethanol-induced hyperhomocysteinemia). Furthermore, it has been reported that homocysteine induces neuronal cell death by stimulating N-methyl-D-aspartate receptors as well as by producing free radicals. To further evaluate this latter hypothesis we analysed serum levels of both homocysteine and markers of oxidative stress (malondialdehyde) in alcoholic patients who underwent withdrawal from alcohol. Homocysteine and malondialdehyde were quantified by high performance liquid chromatography (HPLC) in serum samples of 35 patients (active drinkers). There was a significant correlation (P<0. 01) between blood alcohol concentration and elevated homocysteine (Spearman's r=0.71) and malondialdehyde (r=0.90) levels on admission. In addition, homocysteine and malondialdehyde levels were found to be significant decreased after 3 days of withdrawal treatment (Wilcoxon test: homocysteine, Z=-5.127; malondialdehyde, Z=-3.120; P<0.01). We postulate that excitatory neurotransmitters and mechanisms of oxidative stress in patients with chronic alcoholism may partly mediate excitotoxic neuronal damage and hereby cause brain shrinkage.

Adult↗
PubMed2000

Plasma homocysteine is a predictor of alcohol withdrawal seizures.

An adaptive consequence of prolonged ethanol consumption is a compensatory up-regulation of NMDA receptors in certain brain areas. Taking into account that homocysteine and its breakdown products (i.e. homocysteic acid) are putative neurotransmitters and agonists at the NMDA receptor, the aim of this study was to assess the influence of levels of homocysteine on alcohol withdrawal seizures. Six patients with chronic alcoholism who suffered from withdrawal seizures had significantly higher levels of homocysteine on admission (84.7 +/- 29.8 micromol/l) than patients (n = 26) who did not develop seizures (30.2 +/- 23.2 micromol/l; U = 8.0, p = 0.0007). Furthermore, seizure patients had significantly lower levels of folate and significantly higher blood alcohol concentrations. Using a logistic regression analysis, withdrawal seizures were best predicted by a high homocysteine level on admission (p < 0.01; odds ratio = 1.05). Homocysteine levels on admission may be a useful screening method to identify patients at risk for withdrawal seizures.

Adult↗
PubMed2000

Homocysteine and alcoholism.

Chronic alcohol consumption can induce alterations in the function and morphology of most if not all brain systems and structures. However, the exact mechanism of brain damage in alcoholics remains unknown. Partial recovery of brain function with abstinence suggests that a proportion of the deficits must be functional in origin (i.e. plastic changes of nerve cells) while neuronal loss from selected brain regions indicates permanent and irreversible damage. There is growing evidence that chronic alcoholism is associated with a derangement in the sulfur amino acid metabolism. Recently, it has been shown that excitatory amino acid (EAA) neurotransmitters and homocysteine levels are elevated in patients who underwent withdrawal from alcohol. Furthermore, it has been found that homocysteine induces neuronal cell damage by stimulating NMDA receptors as well as by producing free radicals. Homocysteine neurotoxicity via overstimulation of N-methyl-D-aspartate receptors may contribute to the pathogenesis of both brain shrinkage and withdrawal seizures linked to alcoholism.

Adult↗
PubMed2000

[Follow-up study after enteral manganese poisoning: clinical, laboratory and neuroradiological findings].

Manganese intoxication is an unusual, severe form of intoxication. This report deals with a patient now 80 years old who accidentally ingested a solution of potassium permanganate for a period of at least 4 weeks 14 years ago. Since then, the patient suffers from a mild parkinsonian syndrome and distally accentuated polyneuropathies. Psychiatric disorders, especially demential or depressive symptoms, were not observed. Manganese analysis of his hair still shows a clear increase in manganese concentration. The MRI of his brain showed no pathological changes, in particular none of those often described with symmetric signal elevation in T1 in the area of the basal ganglia. In this study, we present clinical, laboratory, and neuroradiological findings. Unusual in this case with a short exposition is the long duration and clinical improvement without L-dopa treatment.

Aged↗
PubMed2000

Creutzfeldt-Jakob disease and oxidative stress.

OBJECTIVES: Substantial evidence supports the hypothesis that oxygen free radicals are involved in various neurodegenerative disorders. To assess the presence of oxidative stress in Creutzfeldt-Jakob disease (CJD) we examined the concentrations of malondialdehyde (MDA) as an established marker of lipid peroxidation. MATERIAL AND METHODS: MDA was quantified by high performance liquid chromatography (HPLC) in cerebrospinal fluid (CSF; n=12) and in serum (n=11) samples of CJD patients and healthy controls (n = 15). RESULTS: Mean values in healthy controls: 2.56 nmol/ml +/- 0.46 (CSF) and 1.94 nmol/ ml +/- 0.67 (serum); mean values in CJD patients: 2.64 nmol/ml +/- 0.67 (CSF) and 1.68 nmol/ml +/- 0.79 (serum). No significant (P>0.05) difference between CJD patients and controls was observed. CONCLUSIONS: The results indicated that the CSF and serum of CJD patients showed no higher endogenous levels of MDA as compared to normal healthy controls. These findings provide no evidence for an additional role of oxidative stress in the pathogenetic mechanism underlying CJD neurodegeneration.

Biomarkers↗
PubMed2000

A prospective PMS study to validate the sensitivity for change of the D-scale in advanced stages of dementia using the NMDA-antagonist memantine.

The present postmarketing surveillance (PMS) study is the first large scale systematic and prospective clinical trial of pharmacotherapeutic intervention in advanced stages of dementia. Within a validation program this study aimed at demonstrating the sensitivity of the D-Scale of change (DS-C) for measuring ADL-function. Efficacy of treatment with the NMDA-antagonist memantine was investigated in 531 patients with advanced dementia employing a parallel group design that stratified patient cohorts by severity according to GDS stages (Reisberg, 1992). Efficacy was determined on two independent levels: by the assessment of the physicians' Clinical Global Impression of Change (CGI-C) at the end of a 6-week observation period, and by the assessment of change in elementary ADL-functions by the caregivers using the D-Scale-of-Change. With the D-Scale-of-Change the caregivers can assess a change in broad functional items, i.e. cognitive and motor functions and also elementary functions of daily life. The effect size of this improvement increased constantly during the observation period. Even in patients of GDS stage 7 an improvement could be measured. These results were also seen by the physicians, who recorded an overall clinical improvement in 75.5% of the patients after 6 weeks. Tolerability evaluations resulted in the ratings "very well" by 59.5% or "well" by 35.0% of the patients. No serious adverse drug reactions occurred. A correlation analysis demonstrated a high congruency of both assessments. Furthermore, the observed time course of these improvements paralleled with the time course of symptomatic benefit by effects of memantine that had been repeatedly demonstrated in randomised, double-blind, placebo-controlled studies in mild to moderate dementia. Together with the evaluation of the scale-properties of the D-Scale for assessment of severity the D-Scale and the D-Scale-of-Change can be regarded as validated.

Activities of Daily Living↗