The tubular epithelium in the initiation and course of intratubular nephrocalcinosis

Intratubular nephrocalcinosis is defined as the histological observation of calcium oxalate and/or calcium phosphate deposits retained within the lumen of the renal tubules. As the tubular epithelium is the primary interaction partner of crystals formed in the tubular fluid, the role of the epithelial cells in nephrocalcinosis has been investigated intensively. This review summarizes our current understanding on how the tubular epithelium mechanistically appears to be involved both in the initiation and in the course of nephrocalcinosis, with emphasis on in vivo observations.     

Estimation of the wild‐type minimum inhibitory concentration value distribution

Antimicrobial resistance has become one of the main public health burdens of the last decades, and monitoring the development and spread of non‐wild‐type isolates has therefore gained increased interest. Monitoring is performed based on the minimum inhibitory concentration (MIC) values, which are collected through the application of dilution experiments. In order to account for the unobserved population heterogeneity of wild‐type and non‐wild‐type isolates, mixture models are extremely useful. Instead of estimating the entire mixture globally, it was our major aim to provide an estimate for the wild‐type first component only. The characteristics of this first component are not expected to change over time, once the wild‐type population has been confidently identified for a given antimicrobial. With this purpose, we developed a new method based on the multinomial distribution, and we carry out a simulation study to study the properties of the new estimator. Because the new approach fits within the likelihood framework, we can compare distinct distributional assumptions in order to determine the most suitable distribution for the wild‐type population. We determine the optimal parameters based on the AIC criterion, and attention is also paid to the model‐averaged approach using the Akaike weights. The latter is thought to be very suitable to derive specific characteristics of the wild‐type distribution and to determine limits for the wild‐type MIC range. In this way, the new method provides an elegant means to compare distinct distributional assumptions and to quantify the wild‐type MIC distribution of specific antibiotic–bacterium combinations. Copyright © 2013 John Wiley & Sons, Ltd.     

Patterns of antimicrobial therapy in severe nosocomial infections: empiric choices,proportion of appropriate therapy,and adaptation rates—a multicentre,observational survey in critically ill patients

This prospective, observational multicentre (n = 24) study investigated relationships between antimicrobial choices and rates of empiric appropriate or adequate therapy, and subsequent adaptation of therapy in 171 ICU patients with severe nosocomial infections. Appropriate antibiotic therapy was defined as in vitro susceptibility of the causative pathogen and clinical response to the agent administered. In non-microbiologically documented infections, therapy was considered adequate in the case of favourable clinical response <5 days. Patients had pneumonia (n = 127; 66 ventilator-associated), intra-abdominal infection (n = 23), and bloodstream infection (n = 21). Predominant pathogens were Pseudomonas aeruginosa (n = 29) Escherichia coli (n = 26), Staphylococcus aureus (n = 22), and Enterobacter aerogenes (n = 21). In 49.6% of infections multidrug-resistant (MDR) bacteria were involved, mostly extended-spectrum β-lactamase (EBSL)-producing Enterobacteriaceae and MDR non-fermenting Gram-negative bacteria. Prior antibiotic exposure and hospitalisation in a general ward prior to ICU admission were risk factors for MDR. Empiric therapy was appropriate/adequate in 63.7% of cases. Empiric schemes were classified according to coverage of (i) ESBL-producing Enterobacteriaceae and non-fermenting Gram-negative bacteria (“meropenem-based”), (ii) non-fermenting Gram-negative bacteria (schemes with an antipseudomonal agent), and (iii) first-line agents not covering ESBL-Enterobacteriaceae nor non-fermenting Gram-negative bacteria. Meropenem-based schemes allowed for significantly higher rates of appropriate/adequate therapy (p < 0.001). This benefit remained when only patients without risk factors for MDR were considered (p = 0.021). In 106 patients (61%) empiric therapy was modified: in 60 cases following initial inappropriate/inadequate therapy, in 46 patients in order to refine empiric therapy. In this study reflecting real-life practice, first-line use of meropenem provided significantly higher rates of the appropriate/adequate therapy, irrespective of presence of risk factors for MDR.     

Association of Excess Weight and Degree of Airway Responsiveness in Asthmatics and Non-Asthmatics

It is unclear whether obesity is associated with increasing degree of airway responsiveness in asthmatics. In this study, methacholine challenge test results of 1,725 subjects with respiratory symptoms were reviewed. Obesity was associated with asthma with an odds ratio of 1.72 (95% C.I. 1.36, 2.17). Although there was a significant difference in the degree of airway responsiveness between various body mass index categories of non-asthmatics (p = 0.01), no significant difference was noted among asthmatics (p = 0.93). A weakly significant interaction between asthma status and body mass index on the degree of airway responsiveness was noted (p = 0.08).     

Study of the Variability in Upper and Lower Airway Morphology in Sprague–Dawley Rats Using Modern Micro‐CT Scan‐Based Segmentation Techniques

Animal models are being used extensively in pre‐clinical and safety assessment studies to assess the effectiveness and safety of new chemical entities and delivery systems. Although never entirely replacing the need for animal testing, the use of computer simulations could eventually reduce the amount of animals needed for research purposes and refine the data acquired from the animal studies. Computational fluid dynamics is a powerful tool that makes it possible to simulate flow and particle behavior in animal or patient‐specific respiratory models, for purposes of inhaled delivery. This tool requires an accurate representation of the respiratory system, respiration and dose delivery attributes. The aim of this study is to develop a representative airway model of the Sprague–Dawley rat using static and dynamic micro‐CT scans. The entire respiratory tract was modeled, from the snout and nares down to the central airways at the point where no distinction could be made between intraluminal air and the surrounding tissue. For the selection of the representative model, variables such as upper airway movement, segmentation length, airway volume and size are taken into account. Dynamic scans of the nostril region were used to illustrate the characteristic morphology of this region in anaesthetized animals. It could be concluded from this study that it was possible to construct a highly detailed representative model of a Sprague–Dawley rat based on imaging modalities such as micro‐CT scans. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.     

Comparison of dual to single contrast bolus magnetic resonance myocardial perfusion imaging for detection of significant coronary artery disease

Purpose:

To investigate the incremental diagnostic value of dual‐bolus over single‐contrast‐bolus first pass magnetic resonance myocardial perfusion imaging (MR‐MPI) for detection of significant coronary artery disease (CAD).

Materials and Methods:

Patients (n = 49) with suspected CAD underwent first pass adenosine stress and rest MR‐MPI and invasive coronary angiography (CA). Gadolinium diethylenetriamine pentaacetic acid (Gd‐DTPA) was injected with a prebolus (1 mL) and a large bolus (0.1 mmol/kg). For the single‐bolus technique, the arterial input function (AIF) was obtained from the large‐contrast bolus. For the dual‐bolus technique, the AIF was reconstructed from the prebolus. Absolute myocardial perfusion was calculated by Fermi‐model constrained deconvolution. Receiver operating characteristic (ROC) analysis was used to investigate diagnostic accuracy of MR myocardial perfusion imaging for detection of significant CAD on CA at vessel‐based analysis.

Results:

The area under the curve (AUC) of the minimal stress perfusion value for the detection of significant CAD using the single‐bolus and dual‐bolus technique was 0.85 ± 0.04 (95% confidence interval [CI], 0.77–0.93) and 0.77 ± 0.05 (95% CI, 0.67–0.86), respectively.

Conclusion:

In this study the dual‐bolus technique had no incremental diagnostic value over single‐bolus technique for detection of significant CAD with the used contrast concentrations. J. Magn. Reson. Imaging 2010;32:88–93. © 2010 Wiley‐Liss, Inc.     

Sensitivity and specificity of the Leishmania OligoC‐TesT and NASBA‐oligochromatography for diagnosis of visceral leishmaniasis in Kenya

Objective To estimate the sensitivity and specificity of the OligoC‐TesT and nucleic acid sequence‐based amplification coupled to oligochromatography (NASBA‐OC) for molecular detection of Leishmania in blood from patients with confirmed visceral leishmaniasis (VL) and healthy endemic controls from Kenya. Methods Blood specimens of 84 patients with confirmed VL and 98 endemic healthy controls from Baringo district in Kenya were submitted to both assays. Results The Leishmania OligoC‐TesT showed a sensitivity of 96.4% (95% confidence interval [CI]: 90–98.8%) and a specificity of 88.8% (95% CI: 81–93.6%), while the sensitivity and specificity of the NASBA‐OC were 79.8% (95% CI: 67–87%) and 100% (95% CI: 96.3–100%), respectively. Conclusion Our findings indicate high sensitivity of the Leishmania OligoC‐TesT on blood while the NASBA‐OC is a better marker for active disease.