Reninaktivität im Nierenvenenblut und ihre Stimulierbarkeit durch Hydralazin und Theophyllin

Zusammenfassung 1. Es wird über die Plasmareninaktivität im Nierenvenenblut bei 50 Patienten mit primärer und renaler Hypertonie nach Gabe von Hydralazin und Theophyllin berichtet. Die nach diesen Pharmaka beobachtete Stimulation der Reninsekretion beim Gesunden und bei Kranken mit labiler Hypertonie bleibt bei der Mehrzahl der Patienten mit fortgeschrittener primärer Hypertonie aus. Die Stimulierbarkeit bzw. Starre der Reninsekretion durch Natriumentzug zeigt ein analoges Verhalten.2. Ursächlich kommt für den Plasmareninanstieg nach Hydralazin in erster Linie der Blutdruckabfall in Betracht, der zu einer Erregung der Baroreceptoren im terminalen Vas afferens führt. Für Theophyllin wird eine Erregung der Chemoreceptoren an der Macula densa angenommen.3. Die fehlende Stimulierbarkeit der Reninsekretion bei Patienten mit fortgeschrittener primärer Hypertonie, die sich sowohl nach Hydralazin wie nach Theophyllin oder Natriumentzug zeigt, führen wir auf eine verminderte Ansprechbarkeit der Receptoren des juxtaglomerulären Zellkomplexes zurück, die als adaptiver Mechanismus aufgefaßt werden kann.Mit Unterstützung der Deutschen Forschungsgemeinschaft     

Outcomes research analysis of continuous intratympanic glucocorticoid delivery in patients with acute severe to profound hearing loss: basis for planning randomized controlled trials

CONCLUSIONS: The data presented herein form the basis for conducting randomized placebo-controlled clinical trials evaluating the safety and efficacy of salvage treatment in patients with idiopathic sudden severe sensorineural hearing loss (but not anacusis) refractory to initial systemic therapy. Comparison of different application protocols and drug delivery systems will allow assessment of the value of continuous versus intermittent intratympanic glucocorticoid drug delivery. OBJECTIVES: To describe and critically evaluate the results of continuous intratympanic glucocorticoid delivery in patients with acute unilateral severe and profound sensorineural hearing loss refractory to initial systemic therapy and to compare the outcome with a historical control group. MATERIAL AND METHODS: In a retrospective chart review, treatment results were analyzed in 23 patients with acute severe and profound hearing loss and failure of systemic standard therapy who received a continuous intratympanic delivery of glucocorticoids as a salvage treatment. Audiological results were compared within the local therapy group and with the results of an historical control group who did not receive salvage treatment. The study and control groups were matched with respect to hearing loss after initial systemic treatment failure. RESULTS: The average pure-tone threshold after intratympanic salvage treatment showed a statistically significant improvement of 15 dB (95% CI 7-24 dB; p<0.001). After exclusion of patients with complete anacusis, i.e. a non-measurable hearing threshold, the local therapy group showed a significantly better improvement (mean 19 dB; 95% CI 6-32 dB) than the historical control group (mean 5 dB; 95% CI -2-11 dB; p<0.05).     

The voices of wrath: brain responses to angry prosody in meaningless speech

We report two functional magnetic resonance imaging experiments showing enhanced responses in human middle superior temporal sulcus for angry relative to neutral prosody. This emotional enhancement was voice specific, unrelated to isolated acoustic amplitude or frequency cues in angry prosody, and distinct from any concomitant task-related attentional modulation. Attention and emotion seem to have separate effects on stimulus processing, reflecting a fundamental principle of human brain organization shared by voice and face perception.     

The neural correlate of very-long-term picture priming

Repetition priming denotes a behavioural change caused by prior exposure to a stimulus. The effect is known to last for weeks. This study addresses the underlying neural mechanisms for very-long-term picture priming by using event-related functional magnetic resonance imaging complemented by a behavioural paradigm. Previous functional imaging studies with shorter retention intervals have shown that priming is associated with changes in the activity of both the occipital and posterior temporal cortex. In this study we compared retention intervals of 1 day and 6 weeks after initial exposure to a picture stimulus. Priming-related decreases in cortical activity in posterior extrastriate and dorsal left inferior frontal areas were found only for the shorter retention interval. In contrast, fMRI activation in the inferior posterior temporal and anterior left inferior frontal cortex was reduced following priming for both retention intervals. In the behavioural paradigm, the priming effect was stable over time. We conclude that the left inferior frontal and inferior posterior temporal cortex play a key role in the very-long-term priming effect.     

WIN 55,212-2 decreases the spatial spread of neocortical excitation in vitro

The 'intrinsic optical signal' was used to monitor neuronal network excitability. The cannabinoid receptor type 1 agonist WIN 55,212-2 reduced the intensity and the spatial spread of the intrinsic optical signal and prolonged its kinetics in the rat neocortex in vitro. These effects were antagonized by the cannabinoid receptor antagonist SR141716A. Thus, our results suggest that neocortical network activity is modulated via the activation of cannabinoid receptors. The decrease of neocortical network excitability in the present study is probably due to a decreased excitability of glutamatergic neurons.     

EAE in beta-2 microglobulin-deficient mice: axonal damage is not dependent on MHC-I restricted immune responses

There is accumulating evidence that CD8-positive (CD8+) T-cells and MHC-I expression may also play a role in neurodegeneration associated with multiple sclerosis (MS). We investigated the role of MHC-I and CD8+ T-cells by studying experimental autoimmune encephalomyelitis (EAE) in beta-2 microglobulin knockout mice induced by myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 or whole rat myelin basic protein (rMBP). For both encephalitogens and even after reconstitution of the immune system with MHC-I-positive bone marrow and transfer of mature CD8+ T-cells (iMHC-I+ CD8+ beta2m-/- mice), the disease course in beta2m-/- mice was significantly more severe with a 10-fold increased mortality in the beta2m-/- mice as compared to wild-type C57BL/6 mice. EAE in beta2m-/- mice caused more severe demyelination after immunization with MOG than with rMBP and axonal damage was more marked with rMBP as well as MOG even in iMHC-I+ CD8+ beta2m-/- mice. Immunocytochemical analysis of spinal cord tissue revealed a significant increase in macrophage and microglia infiltration in beta2m-/- and iMHC-I+ CD8+ beta2m-/- mice. The different pattern of T-cell infiltration was underscored by a 2.5-fold increase in CD4-positive (CD4+) T-cells in beta2m-/- mice after induction of MOG 35-55 EAE. We conclude that lack of functional MHC-I molecules and CD8+ T-cells aggravates autoimmune tissue destruction in the CNS. Enhanced axonal damage speaks for pathways of tissue damage independent of CD8+ T-cells and neuronal MHC-I expression.     

Colon microflora in infants fed formula with galacto- and fructo-oligosaccharides: more like breast-fed infants

OBJECTIVES: The intestinal flora of breast-fed infants is generally dominated by Bifidobacteria. We aimed to investigate whether an infant formula supplemented with galacto-oligosaccharides and fructo-oligosaccharides (GOS/FOS) is able to establish a bifido-dominant microflora, not only in numbers but also with respect to the metabolic activity in the colon. METHODS: Two groups of infants fed infant formula with 0.8 g/100 ml GOS/FOS in a ratio of 9:1 (OSF group), or control formula (SF group) were evaluated in a randomised, double blind, placebo controlled intervention study. A breast-fed group was studied in parallel. At study onset and after 4 and 6 weeks, faecal samples were examined for the number of bifidobacteria, pH, short chain fatty acids and lactate. RESULTS: After 6 weeks, the mean proportion of bifidobacteria was significantly higher in the OSF group (59.6% versus 49.5% in the SF group; P < 0.05). Compared with controls, infants in the OSF group had a lower stool mean pH and an increased proportion of acetate and a decreased proportion of propionate. The mean pH in the OSF and SF groups were 5.7 and 6.3, respectively (P < 0.001). CONCLUSIONS: The addition of the prebiotic GOS/FOS mixture to an infant formula has a stimulating effect on the growth of bifidobacteria and on the metabolic activity of the total intestinal flora. The changes in short chain fatty acids, lactate and pH in the prebiotic group represent a fermentation profile that is closer to that observed in breast-fed infants compared to infants fed control formula.     

Machine learning approaches for phenotype-genotype mapping: predicting heterozygous mutations in the CYP21B gene from steroid profiles

OBJECTIVE: Non-linear relations between multiple biochemical parameters are the basis for the diagnosis of many diseases. Traditional linear analytical methods are not reliable predictors. Novel nonlinear techniques are increasingly used to improve the diagnostic accuracy of automated data interpretation. This has been exemplified in particular for the classification and diagnostic prediction of cancers based on expression profiling data. Our objective was to predict the genotype from complex biochemical data by comparing the performance of experienced clinicians to traditional linear analysis, and to novel non-linear analytical methods. DESIGN AND METHODS: As a model, we used a well-defined set of interconnected data consisting of unstimulated serum levels of steroid intermediates assessed in 54 subjects heterozygous for a mutation of the 21-hydroxylase gene (CYP21B) and in 43 healthy controls. RESULTS: The genetic alteration was predicted from the pattern of steroid levels with an accuracy of 39% by clinicians and of 64% by linear analysis. In contrast, non-linear analysis, such as self-organizing artificial neural networks, support vector machines, and nearest neighbour classifiers, allowed for higher accuracy up to 83%. CONCLUSIONS: The successful application of these non-linear adaptive methods to capture specific biochemical problems may have generalized implications for biochemical testing in many areas. Nonlinear analytical techniques such as neural networks, support vector machines, and nearest neighbour classifiers may serve as an important adjunct to the decision process of a human investigator not 'trained' in a specific complex clinical or laboratory setting and may aid them to classify the problem more directly.