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Biomedical subjects

G Adler

Publications and source records attributed to G Adler.

At least 37 records · Page 2Linked to original sources

EEG coherence in Alzheimer's dementia.

In Alzheimer's dementia (AD) axonal disruption and cholinergic deficit lead to impaired cortical connectivity and to a decrease in EEG alpha coherence. The aim of the present study was to assess the usefulness of coherence parameters of the EEG for the diagnostics of AD. Quantitative EEG analyses were performed in 31 AD patients and 17 cognitively unimpaired depressive controls, both groups without psychopharmacological treatment. Differences between groups were examined and the diagnostic significance of EEG parameters was assessed by means of stepwise logistic regression analyses. In the AD patients global theta power was increased, left temporal alpha coherence and interhemispheric theta coherence were decreased. Left temporal alpha coherence and global theta power allowed an identification of AD patients with a sensitivity of 87% and a specificity of 77%. Quantitative analyses, especially the determination of left temporal alpha coherence, may enhance the usefulness of the EEG in the diagnostics of AD.

Action Potentials↗

Lipopolysaccharide represses cholesterol 7-alpha hydroxylase and induces binding activity to the bile acid response element II.

BACKGROUND: Inflammatory states such as hepatitis and sepsis are frequently associated with alterations of bile acid synthesis. These conditions are mediated by bacterial wall products like lipopolysaccharide (LPS). Cholesterol 7-alpha hydroxylase is the rate-limiting enzyme of bile acid synthesis. Hydrophobic bile acids repress cholesterol 7-alpha hydroxylase transcription via binding to the farnesoid X receptor and interaction with the bile acid response element II in the cholesterol 7-alpha hydroxylase promoter. METHODS: We tested the effect of LPS on hepatic expression of cholesterol 7-alpha hydroxylase in C57BL/6 mice and Wistar rats. Further, we analyzed the binding activity of hepatic nuclear extracts to the bile acid response element II and the binding site for farnesoid X receptor heterodimers (ecdysone response element). RESULT: Lipopolysaccharide caused a 100-fold reduction of cholesterol 7-alpha hydroxylase mRNA levels in mice and a 10-fold reduction in rats. Protein levels of cholesterol 7-alpha hydroxylase also decreased in both species. These changes inversely correlated with the increased binding activity of nuclear proteins to the bile acid response element II and the ecdysone response element. CONCLUSION: Lipopolysaccharide-induced repression of cholesterol 7-alpha hydroxylase occurs at the transcriptional level. The underlying mechanism involves an increased binding activity of nuclear proteins to the bile acid response element II and the ecdysone response element. In conclusion, the farnesoid and retinoid X receptors participate in LPS-induced cholesterol 7-alpha hydroxylase repression.

Animals↗

[Comparison of conventional enteroclysis, intestinal ultrasound and MRI-enteroclysis for determining changes in the small intestine and complications in patients with Crohn's disease].

BACKGROUND: Enteroclysis, intestinal wall ultrasound (IWU) and abdominal magnetic resonance imaging (MRI) are three established methods in the diagnosis of Crohn's disease (CD). To date, however, the three methods have not been compared in one patient collective. AIMS: The present prospective study compared the relative performance of IWU, MRI and enteroclysis in determining the extent of disease involvement and intestinal complications in patients with CD both at initial diagnosis and during follow-up. PATIENTS AND METHODS: Included in the present study were 48 patients with confirmed CD (age: 19-66 years) examined with all three methods between August 1999 and December 2000. IWU was performed in B-mode with a 4-7 MHz convex transducer head and a 5-12 MHz linear transducer head by an experienced examiner. At MRI, T1 and T2 weighted sequenced (Flash 2D before and after intravenous application of gadolinium DTPA or TSE) were acquired in coronal and transverse planes. Enteroclysis was performed using conventional biphasic technique. Interpretation was conducted on the basis of a standardized catalogue of findings. RESULTS: Changes in bowel segments consistent with inflammation were identified in 41 of 48 patients. All three methods returned equivalent findings with regard to the length of inflamed bowel segments (IWU, range: 3-25 cm, mean: 12 cm; MRI, range: 3-25 cm, mean: 10 cm; enteroclysis, range: 3-30 cm, mean: 11 cm) and wall thickness (IWU, range: 4-10 mm, mean: 7 mm; MRI, range: 5-10 mm, mean: 7 mm; of nine patients with stenotic change, five were correctly diagnosed with IWU (sensitivity, 55.6%; specificity, 97.4%), four with MRI (sensitivity, 44.4%; specificity, 100%) and six with enteroclysis (sensitivity, 66.7%; specificity, 100%). Fistulae were correctly identified in five patients with IWU (sensitivity, 55.6%; specificity, 97.4%), in four with MRI (sensitivity, 44.4%; specificity, 100%) and in six with enteroclysis (sensitivity, 66.7%; specificity, 100 %) of a total of nine patients with confirmed fistula formation. Abscesses were correctly identified in five patients with IWU (specificity, 66.7%; specificity, 100%), in five with MRI (sensitivity, 83.3%; specificity, 100%) and in no patients with enteroclysis (sensitivity, 0%; specificity, 100%) in six patients with abscesses. CONCLUSION: Both IWU and MRI identify extent, severity and intestinal complications with adequate diagnostic accuracy in patients with CD. Both techniques possess the potential for replacing enteroclysis in the work-up of CD. Enteroclysis should be reserved for the work-up of complex fistula systems.

Adult↗

[Quantifying the inflammatory activity in Crohn's disease using CE dynamic MRI].

PURPOSE: Evaluation of dynamic contrast enhanced MRI in patients with Crohn's disease to assess local inflammatory activity. MATERIAL AND METHODS: Prospective study of 13 patients with histologically proven Crohn's disease. Axial and coronal slices were acquired by a 1.5 T MR (Magnetom Vision, Siemens, Germany): T1 flash 2 D (TR 72.5 ms, TE 4.1 ms), T2 (TR 2730 ms, TE 138 ms), turbo-flash sequences T1 (TR 94.2 ms, TE 4.1 ms) post contrast media fat saturated (Magnevist, 0.2 ml/kg, flow 4 ml/s). In area of maximal thickening of terminal ileal wall, axial dynamic T1 sequences (TR 11 ms, TE 4.2 ms) were acquired every 1.5 s post contrast media application for a total duration of 1 min. Contrast uptake was subjectively measured by semiquantitative score and computed assisted ROI evaluation. MR parameters were correlated with CDAI (Crohn's disease activity index) and SAI (severe activity index). RESULTS: Contrast uptake in the intestinal wall occurred after 18.5 s (range: 3.0 - 28.0), contrast upslope until plateau phase lasted for 16.1 s (range: 8.0 - 50.0). Maximum contrast enhancement into the bowel wall was 266 % (105 - 450 %) of baseline. After maximum contrast uptake, we observed a plateau phase in all cases for the total duration of measurement. A significant correlation existed for maximum contrast uptake to CDAI (r = 0.591; p = 0.033), for beginning of contrast upslope to the time until plateau phase (r = 0.822; p = 0.001), and for the time until plateau phase to CDAI (r = 0.562; p = 0.046). CDAI was on average 108, median 106; SAI was on average 114, median 115. SAI correlated significantly to CDAI (r = 0.874). Maximum contrast uptake, beginning of contrast upslope, and time until plateau phase were independent to creeping fat, local lymphadenitis, laboratory parameters, temperature, body mass index, heart frequency and systolic blood pressure. CONCLUSION: Dynamic MRI enables to quantify local inflammatory activity of bowel wall in patients with Crohn's disease. Larger studies are necessary to establish this method in clinical routine.

Adult↗

Short-term effects of acetylcholinesterase inhibitor treatment on EEG and memory performance in Alzheimer patients: an open, controlled trial.

INTRODUCTION: Acetylcholinesterase inhibitor treatment enhances cholinergic neurotransmission and may thus partially reverse EEG slowing and memory impairment in Alzheimer patients within short time. METHODS: We studied the short-term effects of treatment with either rivastigmine or donepezil on EEG and memory performance in a group of 35 Alzheimer patients in an open, controlled design. RESULTS: Under a 1- or 2-week acetylcholinesterase inhibitor treatment, a decrease of global theta power and an improvement in the ADAS memory score were observed. However, compared to the control condition, only the theta power decrease remained significant and can be definitely considered a medication effect. DISCUSSION: EEG spectral analysis could be shown to rapidly reflect the cerebral cholinergic action of short-term acetylcholinesterase inhibitor treatment. Whether this action is related to the therapeutic efficacy of this type of drug must be determined in further longitudinal studies.

Aged↗

Gastrointestinal cancer: towards a tailored tumour therapy.

Major progress has been made in the treatment of metastatic colorectal cancer, but conventional chemotherapy is unlikely to lead to a major breakthrough in the treatment of gastrointestinal tumours. Prognosticators, novel means of early diagnosis of cancer which at the same time indicate prognosis, as well as novel, tumour-specific therapeutic strategies, are urgently needed. There is an increasing amount of promising data from array technology and functional proteomics suggesting that this goal could be achieved in the near future. Research into the mechanisms of cancer signal transduction over the past 20 years has enabled the identification of numerous novel targets for tumour therapy and subsequently the development of various novel drugs termed magic bullets. The in vitro results with these drugs are promising; many drugs lost their magic after the first clinical trials. The state of novel diagnostics and therapeutics in gastrointestinal cancer and the implications for the future treatment of these tumours are discussed in this review.

Antineoplastic Agents↗

[Early diagnosis and treatment of Alzheimer's disease. Implementation in the doctor's office].

The efficacy of antidemential agents proven in comprehensive studies and by clinical experience, now justifies an active and positive approach by the general physician to the diagnosis and treatment of patients with dementia. The proposals on how to implement diagnostic and therapeutic measures in the doctor's office comply both with medical quality criteria and the requirements for appropriateness of treatment and considerations of economy stipulated by German law. They therefore provide the basis for a modern diagnostic work-up and treatment strategy, which will also meet economical demands.

Aged↗

Mechanisms of nordihydroguaiaretic acid-induced growth inhibition and apoptosis in human cancer cells.

Lipoxygenase metabolites of arachidonic acid can act as growth promoting factors for various cancer cell lines. Here we demonstrate that the 5-lipoxygenase inhibitor nordihydroguaiaretic acid potently inhibits anchorage-independent growth of human pancreatic and cervical cancer cells in soft agar and delays growth of pancreatic and cervical tumours established in athymic mice. Furthermore, nordihydroguaiaretic acid induces apoptosis of these cancer cells in vitro and in vivo. Potential mechanisms mediating these effects of nordihydroguaiaretic acid were examined. Nordihydroguaiaretic acid had no inhibitory effect on growth and survival signals such as tyrosine phosphorylation of the epidermal growth factor receptor or basal and growth factor-stimulated activities of extracellular signal-regulated kinase 1/2, p70(s6k) and AKT but selectively inhibited expression of cyclin D1 in the cancer cells. In addition, treatment with nordihydroguaiaretic acid lead to a disruption of the filamentous actin cytoskeleton in human pancreatic and cervical cancer cells which was accompanied by the activation of Jun-NH(2)-terminal kinase and p38(mapk). Similar effects were obtained by treatment of the cancer cells with cytochalasin D. These results suggest that nordihydroguaiaretic acid induces anoikis-like apoptosis as a result of disruption of the actin cytoskeleton in association with the activation of stress activated protein kinases. In conclusion, nordihydroguaiaretic acid could constitute a lead compound in the development of novel therapeutic agents for various types of cancer.

Actins↗

Dyspeptic symptoms in middle-aged to old adults: the role of Helicobacter pylori infection, and various demographic and lifestyle factors.

OBJECTIVES: To evaluate the role of factors supposed to interfere with the gastric mucosa like Helicobacter pylori, smoking and analgesics in symptom generation in a population-based sample of middle-aged to old. SUBJECTS: A total of 288 subjects aged 50-85 (mean 65 +/- 7.2) attending a General Science-orientated Continuing Education Programme at the University of Ulm. METHODS: Helicobacter pylori infection was determined by the 13C-urea breath test. Demographic data, gastrointestinal symptoms and factors supposed to be involved in symptom generation were collected by a standardized questionnaire. The association between various demographic and lifestyle factors with a gastrointestinal symptom score was quantified by odds ratios (ORs) using multiple logistic regression. RESULTS: Use of nonsteroidal anti-inflammatory drugs (OR=1.2; 95% CI=0.7-2.1) was no risk factor for abdominal symptoms, whereas female sex (OR= 1.6; 95% CI=0.9-2.9) and current smoking (OR= 3.7; 95% CI=0.9-15.4) were associated with a high symptom score. Age 70 years and over was significantly associated with a lower symptom score (OR=0.4; 95% CI=0.2-0.9). However, H. pylori infection was a risk factor for a high symptom score in that age group (OR=4.3; 95% CI=1.2-14.8), whereas no such association (and even a tendency to reduced symptom levels in infected subjects) was observed in younger age groups. CONCLUSION: The role of H. pylori infection in symptoms may vary by age. The loss of symptoms in the elderly may delay detection of gastroduodenal pathology and appropriate treatment in older adults.

Age Distribution↗

[Cost measurement based on a cost diary in patients with inflammatory bowel disease].

OBJECTIVE: Cost diaries administered by patients have been used as a method to measure costs for different diseases. Our aim was to test the application of a patient cost diary in patients with inflammatory bowel disease (IBD) and to measure disease specific resource utilization and costs. PATIENTS AND METHODS: A specific patient cost diary for IBD was developed and tested in a prospective pilot study. 105 outpatients with IBD of a University Hospital agreed to participate over a 4 week follow-up period. They were asked to report weekly their use of medical care and costs related to their illness. Visits to health care providers, hospitalizations, drug use, costs due to absence from paid and unpaid work, travel costs as well as out-of-pocket expenses were considered. RESULTS: The response rate was 90 %. Almost 70 % of the patients estimated the diary as easy to fill in. Compared with other data sources, the cost measurement using the cost diary showed good agreement regarding costs of drug therapy and outpatient hospital treatment. Mean costs due to illness were estimated to be 1,500 Euro per 4 weeks. This corresponds to total costs of about 20,000 Euro per year of care. 69 % of total costs were indirect costs due to illness-related absence from work, days of inactivity at home, and early retirement. Direct health care and direct non health care costs (e. g. travel costs) were responsible for 27 % and 4 % of costs, respectively. DISCUSSION AND CONCLUSION: The presented instrument offers a suitable and practical method of assessing IBD-related resource utilization. The prospectively obtained data for direct medical and non medical, as well as indirect costs allow a cost measurement from the societal perspective. The presented cost diary can be used for measuring costs for economic evaluations of medical interventions.

Adult↗

Clozapine in patients with chronic schizophrenia: serum level, EEG and memory performance.

The atypical antipsychotic clozapine causes EEG alterations, and may lead to memory impairments due to its anticholinergic properties. The relationships between clozapine serum level, quantitative EEG parameters and performance in vigilance and memory tasks were studied in a group of 17 chronically ill schizophrenic patients under maintenance treatment with clozapine at stable dosages. There were negative correlations between clozapine serum levels and the amount of high-frequency EEG activity and positive correlations between high-frequency EEG activity and memory performance. These findings may suggest that clozapine treatment brings about dose-dependent impairments of vigilance and memory, for which a reduction of high-frequency EEG activity is indicative.

Adult↗