University of Tübingen

About: University of Tübingen is a education organization based out in Tübingen, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 40555 authors who have published 84108 publications receiving 3015320 citations. The organization is also known as: Eberhard Karls University & Eberhard-Karls-Universität Tübingen.

Ionic mechanisms of electrical remodeling in human atrial fibrillation

Abstract: Objectives: Atrial fibrillation (AF) is associated with a decrease in atrial ERP and ERP adaptation to rate as well as changes in atrial conduction velocity. The cellular changes in repolarization and the underlying ionic mechanisms in human AF are only poorly understood. Methods: Action potentials (AP) and ionic currents were studied with the patch clamp technique in single atrial myocytes from patients in chronic AF and compared to those from patients in stable sinus rhythm (SR). Results: The presence of AF was associated with a marked shortening of the AP duration and a decreased rate response of atrial repolarization. L-type calcium current ( I Ca,L) and the transient outward current ( I to) were both reduced about 70% in AF, whereas an increased steady-state outward current was detectable at test potentials between –30 and 0 mV. The inward rectifier potassium current ( I K1) and the acetylcholine-activated potassium current ( I KACh) were increased in AF at hyperpolarizing potentials. Voltage-dependent inactivation of the fast sodium current ( I Na) was shifted to more positive voltages in AF. Conclusions: AF in humans leads to important changes in atrial potassium and calcium currents that likely contribute to the decrease in APD and APD rate adaptation. These changes contribute to electrical remodeling in AF and are therefore important factors for the perpetuation of the arrhythmia.

Best practices for justifying fossil calibrations

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Detection and identification of fungal pathogens in blood by using molecular probes.

Abstract: A PCR assay was developed for the detection and identification of Candida and Aspergillus species. The design of the oligonucleotide primer pair as well as the species-specific probes used for species identification was derived from a comparison of the sequences of the 18S rRNA genes of various fungal pathogens. The primers targeted a consensus sequence for a variety of fungal pathogens. The assay was tested for sensitivity and specificity with 134 fungal and 85 nonfungal isolates. To assess clinical applicability, 601 blood samples from four defined groups were tested: group A (n = 35), controls; groups B to D (n = 86), patients with febrile neutropenia, without fungal colonization (group B; n = 29) and with fungal colonization (group C; n = 36); and patients with documented invasive fungal infection (IFI) (group D; n = 21). The assay detected and, by species-specific hybridization, identified most of the clinically relevant Candida and Aspergillus species at 1 CFU/ml of blood. Amplification was 100% sensitive for all molds and yeasts tested, with Histoplasma capsulatum being the only non-Aspergillus species hybridizing with the Aspergillus spp. probe. None of 35 group A patients and only 3 of 65 group B and C patients were PCR positive. The sensitivity of the assay for specimens from patients with IFI (21 patients in group D) was 100% if two specimens were tested. For specificity, 3 of 189 specimens from patients at risk but with negative cultures were positive by the assay, for a specificity of 98%. PCR preceded radiological signs by a median of 4 days (range, 4 to 7 days) for 12 of 17 patients with hepatosplenic candidiasis or pulmonary aspergillosis. For the 10 patients with IFI responding to antifungal therapy, PCR assays became persistently negative after 14 days of treatment, in contrast to the case for 11 patients, who remained PCR positive while not responding to antifungal therapy. Thus, the described PCR assay allows for the highly sensitive and specific detection and identification of fungal pathogens in vitro and in vivo. Preliminary data from the screening of a selected group of patients revealed some value in the early diagnosis and monitoring of antifungal therapy.

Interindividual variability of the modulatory effects of repetitive transcranial magnetic stimulation on cortical excitability.

Abstract: Repetitive transcranial magnetic stimulation (rTMS) appears to have effects on cortical excitability that extend beyond the train of rTMS itself. These effects may be inhibitory or facilitatory and appear to depend on the frequency, intensity, duration and intertrain interval of the rTMS. Many studies assume facilitatory effects of high-frequency rTMS and inhibitory effects of low-frequency rTMS. Nevertheless, the interindividual variability of this modulation of cortical excitability by rTMS has not been systematically investigated. In this study, we applied 240 pulses of rTMS at 90% of the subjects' motor threshold to their motor cortex at different frequencies (1, 10, 15 and 20 Hz) and examined the effects on motor evoked potentials (frequency tuning curve). Although the averaged group data showed a frequency-dependent increase in cortical excitability, each subject had a different pattern of frequency tuning curve, i.e. a different modulatory effect on cortical excitability at different rTMS frequencies. The interindividual variability of these modulatory effects was still high, though less so, when the number of rTMS pulses was increased to 1,600. These findings illustrate the degree of variability of the rTMS effects in the human brain.

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus.

Abstract: Cystic fibrosis (CF) is the most common lethal hereditary disorder with autosomal recessive heredity in caucasians. The majority of CF patients suffer from chronic respiratory infection with the opportunistic bacterial pathogen Pseudomonas aeruginosa. No consensus among clinicians has been reached so far concerning antibiotic treatment against P. aeruginosa in CF patients. Consensus answers to 24 important questions in this context, based on current evidence, are presented, given by a panel of 34 European experts. Questions addressed and answered are: The diagnosis of P. aeruginosa lung colonization in CF; The impact of P. aeruginosa on the clinical state of CF patients; The assessment of P. aeruginosa susceptibility against antibiotics and the importance of these results for the clinician; The use of monotherapy versus combination therapy; The development of microbial resistance; The achievement of optimal airway concentrations; The effects of subinhibitory concentrations of antibiotics on P. aeruginosa; Statements on the pharmacokinetics of antibiotics in CF patients; Recommendations for doses and dosing intervals and length of treatment regimens; and Toxic side effects due to repeated antibiotic therapy was addressed. The expert panel answered further questions on the use of fluoroquinolones in children with CF, on the administration of nebulized antibiotics and whether prevention of P. aeruginosa lung colonization is possible in CF using antibiotic therapy. Problems of antibiotic therapy at home and in the hospital were addressed, a consensus statement on regular maintenance treatment, or treatment on demand, was given and different routes of administration of antibiotics were recommended for different clinical situations. Finally, the factors which determine the choice of the antibiotic, the dosage, and the duration of the treatment in cystic fibrosis patients were addressed and the design of future antibiotic studies in the context of Pseudomonas aeruginosa lung infection in cystic fibrosis patients were recommended.