The treatment of helicobacter pylori infection and its sequelae with emphasis on nitroimidazole resistance

In this thesis two different aspects of the treament of Helicobacter pylori (H. pylori) infection are described. The first part (chapters 2-8) explores the epidemiology, mechanism, and clinical significance of nitroimidazole resistance as well as the problems encountered in susceptibility testing for nitroimidazoles. ln the second part (chapters 9 -11) three studies concerning the short and long term sequelae of the treatment of this infection are described.... Zie: Summary

Field-effect based attomole titrations in nanoconfinement

This paper describes a novel capacitive method to change the pH in micro- and nanofluidic channels. A device with two metal gate electrodes outside an insulating channel wall is used for this purpose. The device is operated at high ionic strength with thin double layers. We demonstrate that gate potentials applied between the electrodes cause a release or uptake of protons from the silicon nitride surface groups, resulting in a pH shift in the channel and a titration of solution compounds present. Due to the high quality silicon nitride insulating layer, the effect is purely capacitive and electrolysis can be neglected. Fluorescein was employed as a fluorescent pH indicator to quantify the induced pH changes, and a maximum change of 1.6 pH units was calculated. A linear relationship was found between applied potential and fluorescein intensity change, indicating a linear relation between actuated proton amount and applied voltage. Since this pH actuation method avoids redox reactions and can be operated at physiological ionic strength, it can be very useful as a soft way to change the pH in very small volumes e.g. in bioassays or cell-based research. The sensitivity of the optical detection method poses the only limit to the detectable amount of substance and the observed volume. In a preliminary measurement we show one possible application, namely titration of 100 attomol of TRIS in a 7 pL detection volume. It is important to stress that this pH actuation principle fundamentally differs from the pH changes occurring in ionic transistors which are due to counterion enrichment and coion exclusion, because it does not rely on double-layer overlap. As a result it can be operated at high ionic strength and in channels of up to at least 1 µm height

Field-effect pH Control in Nanochannels

We demonstrate a novel capacitive method to change the pH in nanochannels.\ud The device employs metal electrodes outside an insulating channel wall to change\ud the electrical double layer potential by the field effect (‘voltage gating’). We demonstrate that this potential change is accompanied by a release or uptake of protons from surface groups, resulting in a pH shift in the nanochannel, and a titration of solution compounds present. This pH actuation method avoids redox reactions and can be very useful as a “soft” way to change the pH in small volumes e.g. in bioassays or cell-based research, but also for detection in separation methods. We demonstrate the detection of 100 attomol of TRIS in the detection volume by titration. Importantly, the proton release mechanism does not rely on double layer overlap

Performance of the Montreal classification for inflammatory bowel diseases

AIM: To validate the Montreal classification system for Crohn's disease (CD) and ulcerative colitis (UC) within the Netherlands. METHODS: A selection of 20 de-identified medical records with an appropriate representation of the inflammatory bowel disease (IBD) sub phenotypes were scored by 30 observers with different professions (gastroenterologist specialist in IBD, gastroenterologist in training and IBD-nurses) and experience level with IBD patient care. Patients were classified according to the Montreal classification. In addition, participants were asked to score extra-intestinal manifestations (EIM) and disease severity in CD based on their clinical judgment. The inter-observer agreement was calculated by percentages of correct answers (answers identical to the "expert evaluation") and Fleiss-kappa (kappa). Kappa cutoffs: 0.8 excellent. RESULTS: The inter-observer agreement was excellent for diagnosis (kappa = 0.96), perianal disease (kappa = 0.92) and disease location in CD (kappa = 0.82) and good for age of onset (kappa = 0.67), upper gastrointestinal disease ( kappa = 0.62), disease behaviour in CD (kappa = 0.79) and disease extent in UC (kappa = 0.65). Disease severity in UC was scored poor (kappa = 0.23). The additional items resulted in a good inter-observer agreement for EIM (kappa = 0.68) and a moderate agreement for disease severity in CD ( kappa = 0.44). Percentages of correct answers over all Montreal items give a good reflection of the inter-observer agreement (> 80%), except for disease severity (48%-74%). IBD-nurses were significantly worse in scoring upper gastrointestinal disease in CD compared to gastroenterologists (P = 0.008) and gastroenterologists in training (P = 0.040). Observers with less than 10 years of experience were significantly better at scoring UC severity than observers with 10-20 years (P = 0.003) and more than 20 years (P = 0.003) of experience with IBD patient care. Observers with 10-20 years of experience with IBD patient care were significantly better at scoring upper gastrointestinal disease in CD than observers with less than 10 years (P = 0.007) and more than 20 years (P = 0.007) of experience with IBD patient care. CONCLUSION: We found a good to excellent inter-observer agreement for all Montreal items except for disease severity in UC (poor). (C) 2014 Baishideng Publishing Group Inc. All rights reserved

Image-guided point-shear-wave elastography:a valid and reliable technique for liver fibrotic staging

Purpose: Despite progressive implementation of image-guided point-shear wave elastography (pSWE) in guidelines as an alternative to transient elastography for the staging of fibrotic liver disease, pSWE is not widely adopted in clinical workflow. More information on reliability and validity of pSWE systems is needed. Therefore, we performed a phantom study to evaluate the validity and reliability of pSWE with ultrasound systems. Methods: Validity and reliability of pSWE measurements from three ultrasound systems were evaluated. Measurements were performed on an elasticity phantom with reference elasticities of 7 ± 1 (low) (median ± interquartile range (IQR)), 14 ± 2 (medium) and 26 ± 3 (high) kPa. Measurements were repeated in tenfold for each reference at 2, 3 and 4 cm depth. Results were considered valid when median elasticity ± IQR was between the uncertainty limits (IQR) for each reference elasticity value and reliable when IQR/median &lt; 0.30. Results: pSWE with the systems provided valid results for all reference elasticities and focal depths, except for overestimation of high reference elasticity at 2 and 4 cm depth for one system (41.5 ± 4.3 and 39.0 ± 1.2 kPa, respectively). Measurements were reliable with a maximum IQR/median of 0.13, well below the guideline of IQR/median &lt; 0.30. Discussion: The results support the use of pSWE as an alternative to invasive or non-image guided noninvasive techniques for liver fibrotic staging. Conclusions: pSWE with ultrasound systems from different vendors is valid and reliable and can therefore be implemented to optimize clinical workflow by performing imaging and elastography simultaneously.</p