Zur Analyse der hydrophilen Kolloide in den Kolonien von Paratyphus B

Ohne ZusammenfassungMit 1 Textabbildung.     

Cardiovascular and respiratory hospitalizations and mortality among users of tiotropium in Denmark

Tiotropium (Spiriva is an inhaled, once-daily anticholinergic medication for chronic obstructive pulmonary disease (COPD). We conducted a population-based cohort study to examine the risk of cardiovascular and respiratory hospitalizations and mortality with tiotropium. Using the Danish healthcare registries, we identified persons >/=40 years old in three counties who were hospitalized for COPD from 1/1/1977 to 12/31/2003. Respiratory and cardiovascular medications were assessed from dispensing records. Cox regression was used to compute incidence rate ratios (RR) and 95% confidence intervals (CI) for hospitalization and death between 1/1/2002 and 12/31/2003, associated with periods of tiotropium use compared to non-use, controlling for age, gender, time since COPD, concomitant respiratory and cardiovascular medications, prior hospitalizations and Charlson comorbidity index. Among persons with COPD (10,603), 75% were >/=60 years old. Follow-up was >/=18 months for 64%. Among those exposed to tiotropium compared to periods of non-use, the RR for total and cause-specific hospitalization endpoints were not elevated except for COPD hospitalization (RR = 1.52, 95% CI: 1.29, 1.79). Mortality endpoints included total mortality (RR = 0.77, 95% CI: 0.65, 0.91), respiratory mortality (RR = 0.79, 95% CI: 0.60, 1.04), sudden death (RR = 0.71, 95% CI: 0.21, 2.34), cardiac arrest (RR = 0.74, 95% CI: 0.42, 1.32), heart failure (RR = 0.84, 95% CI: 0.41, 1.75), and myocardial infarction (RR = 1.25, 95% CI: 0.49, 3.17). Compared to periods of non-use, tiotropium was associated with reduced respiratory and overall mortality and was not associated with increased cardiac mortality. An increase in COPD hospitalization is inconsistent with clinical trial data and suggests preferential prescribing due to disease severity.     

Electrical isolation of pulmonary veins in patients with atrial fibrillation: reduction of fluoroscopy exposure and procedure duration by the use of a non-fluoroscopic navigation system (NavX).

AIMS: The aim of the study was to investigate the feasibility of performing segmental pulmonary vein (PV) isolation guided by the NavX (Endocardial Solutions, St Jude Medical, Inc., St Paul, MN, USA) system without the three-dimensional (3D) geometric reconstruction option and whether the use of NavX system will reduce the radiation exposure and procedure duration. METHODS AND RESULTS: The study included 64 patients with symptomatic paroxysmal or permanent atrial fibrillation, in whom PV isolation was performed using fluoroscopic guidance (n=32) or the NavX system (n=32). Pulmonary vein mapping with a circular mapping catheter allowed the identification and localization of myocardial connections between the PV and the left atrium. PV isolation was performed by radiofrequency ablation of these connections at the atrial aspect of the PV ostium. Primary success rate for isolated PVs did not differ significantly in patients ablated under fluoroscopic guidance vs. those ablated under guidance of NavX system [100/107 PVs (93.5%) vs. 120/124 PV (96.8%; P=n.s.)]. Compared with fluoroscopy guided procedures, NavX-guided procedures showed a significant reduction in the fluoroscopy time (75.8+/-24.5 vs. 38.9+/-19.3 min, P<0.05), total X-ray exposure (93.2+/-51.6 vs. 56.6+/-37.9 Gy cm(2), P=0.03), and total procedural time (237.7+/-65.4 vs. 188.6+/-62.7 min, P=0.01). The mean follow-up was 9.5+/-3.0 months. One patient in each group was lost to follow-up. Seven-day Holter monitoring showed that 23 of 31 patients (74.2%) in the NavX-guided group and 21 of 31 patients (67.7%) in the fluoroscopy-guided group were in sinus rhythm (P=0.57). CONCLUSION: The 3D visualization of the catheters by NavX system allows a rapid and precise visualization of the mapping and ablation catheters at the PV ostia and markedly reduces fluoroscopy time, total X-ray exposure, and procedural duration during PV isolation compared with ablation performed under fluoroscopy guidance.     

Schizophrenia and Autism as Contrasting Minds: Neural Evidence for the Hypo-Hyper-Intentionality Hypothesis

Both schizophrenia (SCZ) and autism spectrum disorder (ASD) are characterized by mentalizing problems and associated neural dysfunction of the social brain. However, the deficits in mental state attribution are somehow opposed: Whereas patients with SCZ tend to over-attribute intentions to agents and physical events (“hyper-intentionality”), patients with autism treat people as devoid of intentions (“hypo-intentionality”). Here we aimed to investigate whether this hypo-hyper-intentionality hypothesis can be supported by neural evidence during a mentalizing task. Using functional magnetic resonance imaging (fMRI), we investigated the neural responses and functional connectivity during reading others intention. Scanning was performed in 23 individuals with ASD, 18 with paranoid SCZ and 23 gender and IQ matched control subjects. Both clinical groups showed reduced brain activation compared to controls for the contrast intentional vs physical information processing in left posterior superior temporal sulcus (pSTS) and ventral medial prefrontal cortex (vMPFC) for SCZ, and right pSTS in ASD. As predicted, these effects were caused in a group specific way: Relative increased activation for physical information processing in SCZ that was also correlated with positive PANNS score and relative decreased activation for intentional information processing in ASD. Additionally, we could demonstrate opposed connectivity patterns between the right pSTS and vMPFC in the clinical groups, ie, increased for SCZ, decreased for ASD. These findings represent opposed neural signatures in key regions of the social brain as predicted by the hyper-hypo-intentionality hypothesis.     

Experimental validation of the RATE tool for inferring HLA restrictions of T cell epitopes

Background

The RATE tool was recently developed to computationally infer the HLA restriction of given epitopes from immune response data of HLA typed subjects without additional cumbersome experimentation.

Results

Here, RATE was validated using experimentally defined restriction data from a set of 191 tuberculosis-derived epitopes and 63 healthy individuals with MTB infection from the Western Cape Region of South Africa. Using this experimental dataset, the parameters utilized by the RATE tool to infer restriction were optimized, which included relative frequency (RF) of the subjects responding to a given epitope and expressing a given allele as compared to the general test population and the associated p-value in a Fisher’s exact test. We also examined the potential for further optimization based on the predicted binding affinity of epitopes to potential restricting HLA alleles, and the absolute number of individuals expressing a given allele and responding to the specific epitope. Different statistical measures, including Matthew’s correlation coefficient, accuracy, sensitivity and specificity were used to evaluate performance of RATE as a function of these criteria. Based on our results we recommend selection of HLA restrictions with cutoffs of p-value?<?0.01 and RF?≥?1.3. The usefulness of the tool was demonstrated by inferring new HLA restrictions for epitope sets where restrictions could not be experimentally determined due to lack of necessary cell lines and for an additional data set related to recognition of pollen derived epitopes from allergic patients.

Conclusions

Experimental data sets were used to validate RATE tool and the parameters used by the RATE tool to infer restriction were optimized. New HLA restrictions were identified using the optimized RATE tool.

     

A high and increasing HPV prevalence in tonsillar cancers in Eastern Denmark, 2000–2010: The largest registry‐based study to date

The aim was to explore whether the incidence of tonsillar squamous cell carcinomas (TSCCs) increased in Eastern Denmark, 2000–2010, and whether human papillomavirus (HPV) could explain the increase, and to assess the association of HPV prevalence with gender, age, and origin (i.e., the certainty of tonsillar tumor origin). We applied HPV DNA PCR and p16 immunohistochemistry to all TSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and in the Danish Pathology Data Bank (n = 632). Pathologists reviewed and subdivided the tumors into two groups: specified and nonspecified TSCCs. Approximately 10% of HPV‐positive tumors was genotyped by amplicon next‐generation sequencing. The overall crude incidence of TSCCs increased significantly (2.7% per year) and was explained by an increasing incidence of HPV‐positive TSCCs (4.9% per year). The overall HPV prevalence was 58%, with HPV16 being the predominant HPV type. In multivariate analysis, the HPV prevalence was associated with age (<55 vs. >60 years) (OR, 1.72; 95% CI 1.13–2.63) and origin (nonspecified vs. specified TSCCs) (OR, 0.15; 95% CI 0.11–0.22). The association of HPV prevalence with origin increased over time in specified TSCCs (OR per year, 1.10; 95% CI 1.01–1.19), whereas no change over time was observed among nonspecified TSCCs (OR per year, 0.99; 95% CI 0.90–1.08). In conclusion, the observed increase in the number of HPV‐positive TSCCs can explain the increasing number of TSCCs in Eastern Denmark, 2000–2010. HPV prevalence was associated with younger age (<55 years) and a high certainty of tonsillar tumor origin.