The Alzheimer variant of Lewy body disease: A pathologically confirmed case-control study

The objective of the study was to identify clinical features that distinguish patients with dementia with Lewy bodies (DLB), who were classified as Alzheimer's disease ( AD) patients, from patients with AD. We examined a group of 27 patients from our memory clinic, originally diagnosed with AD, of whom 6 were postmortem found to have DLB. For the present study, we compared cognitive, noncognitive and neurological symptoms between the two groups. We found that there were no differences on ratings of dementia and scales for activities of daily living. Patients with DLB performed better on the MMSE and the memory subtest of the CAMCOG, but there was no difference in any other cognitive domain. Furthermore, genetic risk factors, including family history of dementia or allele frequency of the apolipoprotein epsilon 4, did not discriminate between the two groups, and there were no differences on CCT scans. Taken together, our findings suggest that Lewy body pathology may be present in patients who do not show the typical clinical features which distinguish DLB from AD. Copyright (C) 2005 S. Karger AG, Basel

Intracellular free sodium and potassium, post-carbachol hyperpolarization, and extracellular potassium-undershoot in rat sympathetic neurones

Double-barrelled ion-sensitive microelectrodes were used to record the free intracellular Na+- and K+-concentrations ([Na+]i, [K+]i) and to determine their relation to changes in membrane potential and extracellular K+ ([K+]e) in rat sympathetic ganglia. The application of 50 μmol/l carbachol resulted in an elevation of [K+]e followed by a post-carbachol [K+]e-undershoot. The membrane depolarization of the sympathetic neurones was associated with an increase in [Na+]i and a decrease in [K+]i. A membrane hyperpolarization and a recovery of [K+]i and [Na+]i to their baseline levels were observed during the [K+]e-undershoot. The time course of the [K+]e-undershoot correlated exactly with the duration of the rise in [Na+]i and decrease of [K+]i. No K+-reuptake occurred in the presence of ouabain. These data confirm, by direct measurements of intracellular ion concentration changes, the contribution of the Na+, K+-pump to the post-carbachol membrane hyperpolarization and [K+]e-undershoot

Zellbiologische Charakterisierung kutaner Keloide - eine in-vitro-Studie

Bei Keloiden handelt es sich aus klinischer Sicht um gutartige, fibroproliferative Hauttumore, welche eine progressive Form der gestörten Wundheilung darstellen und bisher nur beim Menschen beobachtet werden konnten. Sie infiltrieren durch Überschreitung der ursprünglichen Begrenzung der Wunde das gesunde Nachbargewebe und zeigen keine Tendenz zur spontanen Rückbildung. Sie stellen in vielfacher Weise eine große Belastung für den Patienten dar, oftmals in Form von Schmerzen, Jucken sowie ästhetischer oder auch funktioneller Einschränkung. Keloide stellen zudem eine große Herausforderung für den behandelnden Arzt dar. Trotz einer großen Vielfalt an Therapieoptionen existiert noch keine definitiv wirksame, nebenwirkungs- oder rezidivfreie Therapieform, was wiederum das eingeschränkte Verständnis des genauen Pathomechanismus sowie der molekularen Zusammenhänge dieser Wundheilungsstörung wiederspiegelt. Im Rahmen dieser Dissertation sollten das Proliferationsverhalten und die Sekretion wundheilungsrelevanter Wachstumsfaktoren und Zytokine von patientenspezifischen Keloidkulturen auf zellulärer Ebene in vitro charakterisiert werden, sowohl unter Standardbedingungen als auch unter definierter Beeinflussung des Wachstumsmilieus. Zu diesem Ziel erfolgte die Aussaat von Keloidfibroblasten (KF) aus sechs verschiedenen patientenspezifischen Kulturen und normaler dermaler Fibroblasten als Kontrolle (NHF). Die Beurteilung der Zellviabilität unter Standardbedingungen erfolgte mittels Resazurin-Assay und Fluoreszenzmessung nach 72 h Inkubation sowie durch Aussaat in einem 6-Well-System und Inkubation für 96 h mittels anschließender Zellzählung. Es zeigte sich eine signifikant geringere Proliferation bei allen Keloidkulturen gegenüber NHF als Kontrolle. Auch die Ergebnisse der einzelnen Keloidkulturen zeigten im Vergleich untereinander signifikante Schwankungen. Die Analyse der Protein- und Genexpression der Keloidfibroblasten unter Standardbedingungen zeigte eine gegenüber den NHF signifikant verringerte Syntheseleistung für IL-6, aber eine um ein Vielfaches verstärkte Expression von VEGF. Es bestätigte sich, dass VEGF ein durchaus bedeutender Faktor in der Pathogenese der Keloide und letztlich auch für die Keloidtherapie sein könnte. Die Rolle von IL-6 blieb in diesem Zusammenhang aufgrund der individuellen Unterschiede unklar. Des Weiteren wurde eine Darstellung des Einflusses mechanischer Krafteinwirkung in Form zyklischer Dehnung im Minutentakt für 72 h während der Kultivierung angestrebt. So sollte die Rolle dieses Faktors im Rahmen der Keloidpathogenese und eines komplikationsarmen Heilungsverlaufs nach Keloidexzision eruiert werden. Es ergab sich weder bei den NHF noch bei den KF eine signifikant veränderte Proliferation bei den gedehnten Proben im Vergleich zur ungedehnten Kontrolle. Auch die Proteinexpression von VEGF sowie IL-6 war weder bei den NHF noch bei den Keloidfibroblasten signifikant verändert unter dem Einfluss der Dehnung. Als drittes Ziel sollte ermittelt werden, ob der therapeutische Effekt von Botulinumtoxin A in der Keloidbehandlung anhand patientenspezifischer Keloidgewebeproben auf zellulärer Ebene reproduzierbar ist und sich so eine positive Wirkung von Botulinumtoxin A in der Therapie begründen ließe. Ferner sollte analysiert werden, ob für die Wundheilung relevante Zytokine und Wachstumsfaktoren unter dem Einfluss von Botulinumtoxin A entscheidend moduliert werden. Es wurden Konzentrationen von 1 IU, 2.5 IU, 5 IU und 10 IU Botulinumtoxin A im Resazurin-Assay eingesetzt sowie 1 IU und 2.5 IU bei Inkubation im 6-Well-System für 72 h. In beiden Fällen gab es zusätzlich einen Versuchsansatz ohne Botulinumtoxin A als Kontrolle. Es zeigte sich weder bei den NHF noch bei den KF eine signifikante Veränderung der Zellproliferation bei einer der Konzentrationen von Botulinumtoxin A im Vergleich zur Kontrolle. Auch die Untersuchung der Proteinexpression von IL-6, VEGF und TGF-ß1 ergab keine signifikante Veränderung unter dem Einfluss der Inkubation mit Botulinumtoxin A im Vergleich zur Kontrolle

Changes in extracellular pH during electrical stimulation of isolated rat vagus nerve

Double-barrelled pH-sensitive micro-electrodes were used to record changes of extracellular pH during repetitive stimulation of isolated rat vagus nerves. It was found that a small initial alkaline shift was followed by a prolonged acidification. The acidification was correlated in time with the poststimulus undershoot of the extracellular K+ activity and with the recovery phase of the nerve conduction velocity. In the presence of ouabain, the acid component of the pH change was completely abolished (indicating a metabolic origin), whereas the alkaline component remained unaltered. These pH changes were too small to make a significant contribution to the activity-related changes in conduction velocity of the vagal C-fibres

Paramnestic reduplication of Charles Bonnet and Theophile Bonet

An elderly woman developed the delusion that she was dead (‘Cotard's delusion’) and that she was in another place (‘reduplicative paramnesia’). Charles Bonnet reported this unique combination of symptoms a century before Cotard's influential description of the nihilistic delusions and of Pick's description of ‘reduplicative paramnesia’

Why Is It So Difficult to Evaluate Nursing Interventions in Dementia?

Two recent health technology assessment (HTA) reports published in Germany focused on non-pharmacological interventions for patients with dementia. One of the major results was the poor methodological quality of the studies in this field. This paper concisely presents the main quantitative and qualitative findings of the HTA report published by the German Agency for HTA at the Institute of Medical Information and Documentation (dahta@DIMDI), followed by a detailed discussion of the major methodological problems observed for the inclusion criteria, interventions, the setting, number of patients included, duration of observation, comparators, clinical endpoints, health economics, and, most obvious, the impossibility of blinding and eliminating placebo effects for future clinical studies. We conclude with several suggestions addressing these challenges for future research in this field

Predicting dementia in primary care patients with a cardiovascular health metric: a prospective population-based study

Background: Improving cardiovascular health possibly decreases the risk of dementia. Primary care practices offer a suitable setting for monitoring and controlling cardiovascular risk factors in the older population. The purpose of the study is to examine the association of a cardiovascular health metric including six behaviors and blood parameters with the risk of dementia in primary care patients. Methods: Participants (N = 3547) were insurants aged >= 55 of the largest German statutory health insurance company, who were enrolled in a six-year prospective population-based study. Smoking, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose were assessed by general practitioners at routine examinations. Using recommended cut-offs for each factor, the patients' cardiovascular health was classified as ideal, moderate, or poor. Behaviors and blood parameters sub-scores, as well as a total score, were calculated. Dementia diagnoses were retrieved from health insurance claims data. Results are presented as hazard ratios (HRs) and 95 % confidence intervals (95 % CIs). Results: Over the course of the study 296 new cases of dementia occurred. Adjusted for age, sex, and education, current smoking (HR = 1.77, 95 % CI 1.09-2.85), moderate (1.38, 1.05-1.81) or poor (1.81, 1.32-2.47) levels of physical activity, and poor fasting glucose levels (1.43, 1.02-2.02) were associated with an increased risk of dementia. Body mass index, blood pressure, and cholesterol were not associated with dementia. Separate summary scores for behaviors and blood values, as well as a total score showed no association with dementia. Sensitivity analyses with differently defined endpoints led to similar results. Conclusions: Due to complex relationships of body-mass index and blood pressure with dementia individual components cancelled each other out and rendered the sum-scores meaningless for the prediction of dementia

More Consistently Altered Connectivity Patterns for Cerebellum and Medial Temporal Lobes than for Amygdala and Striatum in Schizophrenia

Background: Brain architecture can be divided into a cortico-thalamic system and modulatory "subcortical-cerebellar" systems containing key structures such as striatum, medial temporal lobes (MTLs), amygdala, and cerebellum. Subcortical-cerebellar systems are known to be altered in schizophrenia. In particular, intrinsic functional brain connectivity (iFC) between these systems has been consistently demonstrated in patients. While altered connectivity is known for each subcortical-cerebellar system separately, it is unknown whether subcortical-cerebellar systems' connectivity patterns with the cortico-thalamic system are comparably altered across systems, i.e., if separate subcortical-cerebellar systems' connectivity patterns are consistent across patients. Methods: To investigate this question, 18 patients with schizophrenia (3 unmedicated, 15 medicated with atypical antipsychotics) and 18 healthy controls were assessed by resting-state functional magnetic resonance imaging (fMRI). Independent component analysis of fMRI data revealed cortical intrinsic brain networks (NWs) with time courses representing proxies for cortico-thalamic system activity. Subcortical-cerebellar systems' activity was represented by fMRI-based time courses of selected regions-of interest (ROls;i.e., striatum, MTL, amygdala, cerebellum). Correlation analysis among ROI- and NWs time courses yielded individual connectivity matrices [i.e., connectivity between NW and ROls (alIROls-NW, separateROI-NW), only NWs (NWs-NWs), and only ROls (alIROls-alIROls)] as main outcome measures, which were classified by support-vector-machine-based (SVM) leave-one-out cross-validation. Differences in classification accuracy were statistically evaluated for consistency across subjects and systems. Results: Correlation matrices based on aIIROls-NWs yielded 91% classification accuracy, which was significantly superior to alIROls-alIROls and NWs-NWs (56 and 74%, respectively). Considering separate subcortical-cerebellar systems, cerebellum NWs and MTL-NWs reached highest accuracy values with 91 and 85%, respectively, while those of striatum-NW and amygdala-NW were significantly lower with about 65% classification accuracy. Conclusion: Results provide initial evidence for differential consistency of altered intrinsic connectivity patterns between subcortical-cerebellar systems and the corticothalamic system. Data suggest that differential dysconnectivity patterns between subcortical-cerebellar and cortical systems might reflect different disease states or patient subgroups