Ohne Zusammenfassung

Objectives This study describes the 5-year efficacy of catheter ablation for long-standing persistent atrial fibrillation (LS-AF).Background Long-term outcome data after catheter ablation for LS-AF are limited.Methods Long-term follow-up of 56 months (range 49 to 67 months) was performed in 202 patients (age 61 +/- 9 years) who underwent the sequential ablation strategy for symptomatic LS-AF. Initial ablation strategy was circumferential pulmonary vein isolation (PVI). Additional ablation was performed only in acute PVI nonresponder, if direct current cardioversion failed after PVI.Results After the first ablation procedure, sinus rhythm was documented in 41 of 202 (20.3%) patients. After multiple procedures, sinus rhythm was maintained in 91 of 202 (45.0%) patients, including 24 patients receiving antiarrhythmic drugs. In 105 patients, PVI was the sole ablative therapy, 49 (46.7%) of those patients remained in sinus rhythm during follow-up. Patients with a total AF duration of <2 years had a significantly higher ablation success rate than patients whose AF duration was <2 years (76.5% vs. 42.2%, respectively; p = 0.033). Persistent AF duration (hazard ratio: 1.09 [95% confidence interval: 1.04 to 1.13]; p < 0.001) independently predicted arrhythmia recurrences, and acute PVI responders had a reduced risk of relapse (hazard ratio: 0.57 [95% confidence interval: 0.41 to 0.78]; p < 0.001) after the first ablation.Conclusions During 5-year follow-up, single-and multiple ablation procedure success was 20% and 45%, respectively, for patients with LS-AF. For patients with a total AF duration of <2 years, the outcomes were favorable. (J Am Coll Cardiol 2012;60:1921-9) (C) 2012 by the American College of Cardiology Foundation

Objectives: Recurrent Major Depression (MD) is accompanied by alterations in temporal lobe structures and deficits in verbal declarative memory. This study investigated the frequency of atypical language dominance and verbal declarative memory function in patients with MD. Methods: 21 right-handed patients (Age: 54,4 ± 14,7) with recurrent MD were investigated with fTCD and a lexical word generation paradigm. Cerebral blood velocities (CBFV)in both middle cerebral arteries were analyzed with the software Average®. Relative increase in CBFV during word generation compared to resting was computed. From the interhemispheric differences, a lateralization index (LI) was calculated. Severity of depressive symptomatology was assessed with The Montgomery Asberg Depression Rating Scale (MADRS). Results: Depressive patients showed more frequently an atypical language dominance than healthy controls (29% vs. 9%; p < .05). Depressive patients and controls with atypical language dominance showed no differece in LI(3,9 vs. 4,3 p > .1). The maximal relative increase in CBFV, in both middle cerebral arteries, was significantly decreased in MD compared to controls (ACM links 8,7% vs. 14,0%, ACM rechts 7,0% vs. 11,2%; p < .01). Conclusions: We found preliminary evidence that the incidence of atypical language lateralization is increased in patients with recurrent depression, although the pathophysiological basis underlying this association remains unclear and should be addressed in further studies.

Aim: This study investigated frequency of atypical language dominance and its association to verbal memory in patients with schizophrenia and in healthy controls. Methods: In 18 right-handed patients (age: 39.6±12.5y) and 35 controls (age: 56.4±8.9y) language dominance was determined with functional transcranial Doppler sonography (fTCD): Cerebral blood flow velocity (CBFV) was measured continuously in both middle cerebral arteries (MCA) while conducting a word generation paradigm. Relative CBFV increase during word generation compared to resting and a laterality index (LI) representing the side difference in rCBFV were computed. Verbal memory (VLMT) and vocabulary (WST) was measured using established neuropsychological tests. Psychiatric symptoms were rated with the Brief Psychiatric Rating Scale (BPRS). Results: Frequency of atypical language dominance was similar in patients and controls (7% vs. 9%; p>0.1). RCBFV increase was lower in patients (left MCA: 10.5% vs. 14.0%; right MCA: 6.7% vs. 11.2%, p<0.05) and patients showed reduced verbal learning (p<0.01). In patients with a relatively strong left-sided language dominance (Median-Split) word recognition was by trend worse compared to patients with weaker left-sided dominance (p<0.1). Conclusion: A higher rate of atypical language dominance was not observed in schizophrenic patients. In patients, weaker language dominance seemed to be advantageous with respect to word recognition as a parameter of verbal memory.

Fragestellung: Bei schizophrenen Patienten sind Verbalgedächtnisdefizite gut beschrieben. Studien verweisen auf linkstemporale metabolische sowie strukturelle Veränderungen. Die vorliegende Studie untersuchte daher die Frequenz verschiedener Sprachdominanzen sowie verbale Gedächtnisleistungen bei Patienten mit Schizophrenie.

Fragestellung: Bei der Major Depression werden funktionelle und strukturelle Einschränkungen im Bereich des Temporallappens sowie Gedächtnisbeeinträchtigungen beschrieben.

Cortisol secretion is closely related to stress stimulation, learning and memory functions. To evaluate the effects of a stress induced cortisol secretion on memory function, we applied a computer based learning task in 48 healthy male subjects (age 18–34 years). This task had to be performed with (stress condition) and without (baseline) a time limitation. Both conditions were randomly assigned and completely balanced. Different learning parameters (e.g. number of trials to reach a learning criterion) were assessed. Cortisol samples were obtained from saliva. The stress condition resulted in significant higher cortisol levels compared to baseline learning without stress, accompanied by increased systolic and diastolic blood pressure, heart rate and subjective stress parameters. Cortisol increase during stressful learning was not related to learning performance. However, there was a trend that subjects with a stronger increase of cortisol during stressful learning performed worse in delayed free recall after the experiment. In contrast, increase in diastolic blood pressure was associated with lower task performance. Mood changes were associated with learning performance but not with delayed free recall. In summary, the stressful learning task was able to provoke a stress response in healthy volunteers on the endocrine, cardiovascular and subjective level, somewhat affecting memory performance.

Creativity plays an important role in numerical problem solving. Although the neural underpinnings of creativity have been studied over decades, very little is known about neural mechanisms of the creative process that relates to numerical problem solving. In the present study, we employed a numerical analogical reasoning task with functional Magnetic Resonance Imaging (fMRI) to investigate the neural correlates of divergent production of rules in numerical analogical reasoning. Participants performed two tasks: a multiple solution analogical reasoning task and a single solution analogical reasoning task. Results revealed that divergent production of rules involves significant activations at Brodmann area (BA) 10 in the right middle frontal cortex, BA 40 in the left inferior parietal lobule, and BA 8 in the superior frontal cortex. The results suggest that right BA 10 and left BA 40 are involved in the generation of novel rules, and BA 8 is associated with the inhibition of initial rules in numerical analogical reasoning. The findings shed light on the neural mechanisms of creativity in numerical processing.

Besides cognitive impairment, patients with dementia commonly present with a sleep disturbance. The most robust polysomnographic finding in Alzheimer’s dementia (DAT) is reduction of REMsleep. Cholinsterase inhibitors (Che-I) are able to increase REM-sleep in volunteers. The objective of this study was to evaluate the effects of Che-I on REM-sleep in DAT and frontotemporal dementia (FTD) during long-term treatment. So far, 13 patients with low to moderate dementia could be examined. 7 patients were classified as having DAT and 6 patients as having FTD. A polysomnography was performed in all patients who were free of psychotropic medication before therapy with a Che-I and after 5–10 months, while patients were on monotherapy with a Che-I. In all patients sleep continuity disruption was observed. In DAT a more accentuated REM sleep reduction in comparison to FTD was found. Treatment with Che-I did not improve sleep continuity. However, REM-sleep increased in patients with DAT, but not in patients with FTD. Furthermore, REM-latency was reduced in DAT after treatment with Che-I. The observed REMsleep reduction in patients with DAT compared to FTD may suggest that cholinergic neurotransmission is more impaired in DAT than in FTD. However, it remains unclear whether the increase of REM-sleep after long-term treatment with Che-I in DAT may only reflect a mere pharmacological effect or whether this increase may be related to the efficacy of anti-dementia treatment

Disturbance of sleep-wake pattern is a prominent feature in patients with dementia. In an ongoing study polysomngraphy was registered in 18 patients including dementia of Alzheimer (AD) and Lewy body type and frontotemporal dementia (FTD). In five patients with a monotherapy of donepezil or galantamine over two months sleep EEG could be assessed twice.

Patienten mit Demenz leiden an einer erheblichen Störung des Schlaf-Wach-Rhythmus. Nur in wenigen Studien wurde bisher eine polysomnographische Evaluation des Schlafs von Patienten mit Demenz vorgenommen. In diesen Studien, die vorwiegend an Patienten mit M. Alzheimer (AD) durchgeführt wurden, zeigte sich neben einer Störung der Schlafkontinuität v.a. eine Reduktion des REM-Schlafs. In einer Studie bei Patienten mit Lewy Körperchen Demenz finden sich neben einer gestörten Schlafkontinuität vermehrt periodische Beinbewegungen im Schlaf im Vergleich zu Patienten mit AD. Bei Patienten mit frontotemporaler Demenz wurde der Schlaf bisher kaum untersucht.

Mirtazapine is a novel antidepressant with sleep promoting effects. In an ongoing study we evaluated the short term (after one week of treatment) and long term effects (after six weeks) of mirtazepine on polysomnography in 6 patients with major depression in comparison to the polysomngraphic effects of venlafaxine.

Patienten mit Demenz leiden neben ihrer kognitiven Störung an einer Störung des Schlaf-Wach-Rhythmus, die häufig durch eine nächtliche Unruhe und ein Schlafverhalten während des Tages gekennzeichnet ist. Nur in wenigen Studien wurde bisher der Schlaf von Patienten mit Demenz polysomnographisch untersucht. In diesen Studien, die vorwiegend an Patienten mit Morbus Alzheimer durchgeführt wurden, zeigte sich neben einer Störung der Schlafkontinuität vor allem eine Reduktion des REM-Schlafs. In einer Studie bei Patienten mit Lewy Körperchen-Demenz finden sich neben einer gestörten Schlafkontinuität vermehrt periodische Beinbewegungen im Schlaf. Bei Patienten mit frontotemporaler Demenz wurde der Schlaf bisher nicht systematisch untersucht. In der noch laufenden Studie konnte bei bisher 18 Patienten ohne psychotrope Medikation eine Polysomnographie abgeleitet werden. Zehn Patienten (5 Männer, 5 Frauen, Alter 73,6±6,5 Jahre) litten an einer Demenz vom Alzheimer-Typ, sechs hatten eine frontotemporale Demenz (3 Männer, 3 Frauen, Alter 57,8±11,3 Jahre), bei zwei Patienten bestand der dringende Verdacht auf eine Lewy Körperchen-Demenz. Bei allen Patienten wurde zudem eine neuropsychologische Testung mit der CERAD-Testbatterie vorgenommen. Die Ergebnisse der bisher vorliegenden Daten zeigen, dass bei allen Patienten eine deutliche Störung der Schlafkonituität vorliegt und diese meist stärker ausgeprägt ist, als sie subjektiv wahrgenommen wird. Der REM-Schlaf war bei Patienten mit Morbus Alzheimer im Vergleich zu Patienten mit frontotemporaler Demenz reduziert. Zudem wurde bei Patienten mit Morbus Alzheimer häufig und bei einem Patienten mit Lewy Körperchen-Demenz das Auftreten von schlafbezogenen Atemstörungen gefunden, nicht aber bei frontotemporaler Demenz. Die Störung der Schlafkontinuität war nicht mit der in der CERAD-Testbatterie erhobenen kognitiven Leistung korreliert. Die bisherigen Ergebnisse dieser Studie zeigen, dass Störungen der Schlafkontinuität bei Patienten mit Demenz häufig auftreten und meist stärker ausgeprägt sind als dies von den Patienten selbst wahrgenommen wird. Zudem findet sich bei Patienten mit Morbus Alzheimer eine deutliche Reduktion des REM-Schlafs, die in dieser Studie bei Patienten mit frontotemporaler Demenz weit geringer ist. Bei vielen der untersuchten Morbus Alzheimer-Patienten wurden zudem klinisch relevante schlafbezogene Atemstörungen und auch periodische Beinbewegungen im Schlaf entdeckt, die mit der Störung des polysomnographischen Profils in Zusammenhang stehen und auch zur kognitiven Leistungsminderung beitragen könnten.

Six inpatients, four with major depression and two with schizophrenia were included. All patients underwent 72-h actigraphic monitoring and were evaluated by a number of psychiatric rating scales. The same procedure was repeated after four weeks of treatment for the severely depressed patients.

These in vitro studies aimed to characterize the pattern and the kinetics of endoproteolysis of the insulinotropic hormone glucagon-like peptide-1 (GLP-1) and related peptides by native ectopeptidases. Peptides were incubated with isolated rat or pig kidney brush-border microvilli membranes, which are a rich source of the ectopeptidases that are responsible for the post-secretory metabolism of peptide hormones. The proteolytic products were separated by reversed-phase HPLC column chromatography and characterised by molecular mass and primary structure. The relative importance of specific peptidases was established by measuring the effects of specific peptidase inhibitors on the kinetics of proteolysis. Dipeptidyl-peptidase-IV was found to be rate-limiting in the endoproteolysis of GLP-1. GLP-1 homologs, exendins-3 and -4, exhibited exceptional stability in the presence of isolated kidney microvilli membranes. Our finding that exendin-4 is several orders of magnitude more stable than GLP-1 and Ser-8-GLP-1 is especially noteworthy given this peptide's widely reported insulinotropic potency.