587 research outputs found
Tidal Volume Single Breath Washout of Two Tracer Gases - A Practical and Promising Lung Function Test
Small airway disease frequently occurs in chronic lung diseases and may cause ventilation inhomogeneity (VI), which can be assessed by washout tests of inert tracer gas. Using two tracer gases with unequal molar mass (MM) and diffusivity increases specificity for VI in different lung zones. Currently washout tests are underutilised due to the time and effort required for measurements. The aim of this study was to develop and validate a simple technique for a new tidal single breath washout test (SBW) of sulfur hexafluoride (SF(6)) and helium (He) using an ultrasonic flowmeter (USFM)
Identification of conformational epitopes for human IgG on Chemotaxis inhibitory protein of Staphylococcus aureus
<p>Abstract</p> <p>Background</p> <p>The Chemotaxis inhibitory protein of <it>Staphylococcus aureus </it>(CHIPS) blocks the Complement fragment C5a receptor (C5aR) and formylated peptide receptor (FPR) and is thereby a potent inhibitor of neutrophil chemotaxis and activation of inflammatory responses. The majority of the healthy human population has antibodies against CHIPS that have been shown to interfere with its function <it>in vitro</it>. The aim of this study was to define potential epitopes for human antibodies on the CHIPS surface. We also initiate the process to identify a mutated CHIPS molecule that is not efficiently recognized by preformed anti-CHIPS antibodies and retains anti-inflammatory activity.</p> <p>Results</p> <p>In this paper, we panned peptide displaying phage libraries against a pool of CHIPS specific affinity-purified polyclonal human IgG. The selected peptides could be divided into two groups of sequences. The first group was the most dominant with 36 of the 48 sequenced clones represented. Binding to human affinity-purified IgG was verified by ELISA for a selection of peptide sequences in phage format. For further analysis, one peptide was chemically synthesized and antibodies affinity-purified on this peptide were found to bind the CHIPS molecule as studied by ELISA and Surface Plasmon Resonance. Furthermore, seven potential conformational epitopes responsible for antibody recognition were identified by mapping phage selected peptide sequences on the CHIPS surface as defined in the NMR structure of the recombinant CHIPS<sub>31–121 </sub>protein. Mapped epitopes were verified by <it>in vitro </it>mutational analysis of the CHIPS molecule. Single mutations introduced in the proposed antibody epitopes were shown to decrease antibody binding to CHIPS. The biological function in terms of C5aR signaling was studied by flow cytometry. A few mutations were shown to affect this biological function as well as the antibody binding.</p> <p>Conclusion</p> <p>Conformational epitopes recognized by human antibodies have been mapped on the CHIPS surface and amino acid residues involved in both antibody and C5aR interaction could be defined. This information has implications for the development of an effective anti-inflammatory agent based on a functional CHIPS molecule with low interaction with human IgG.</p
Lung Clearance Index (LCI) is Stable in Most Primary Ciliary Dyskinesia (PCD) Patients Managed in a Specialist Centre:a Pilot Study
Primary ciliary dyskinesia is a condition in which abnormal cilia structure or function leads to reduced mucociliary clearance and obstructive lung disease. Twenty-nine patients had lung clearance index (LCI) measured in 2009 and we attempted to perform a 5-year follow-up. Only 12 patients could be re-recruited, but in this small group LCI was stable over the 5 years, which confirms previous data showing that spirometry is also stable in these patients over the medium term. The two patients with the highest LCI in 2009 had since died, despite one having relatively preserved spirometry at the time. These data may be used to inform sample size calculations of future studies
Gastroesophageal reflux disease in 2006: The imperfect diagnosis
There continues to be significant controversy related to diagnostic testing for gastroesophageal reflux disease (GERD). Clearly, barium contrast fluoroscopy is superior to any other test in defining the anatomy of the upper gastrointestinal (UGI) tract. Although fluoroscopy can demonstrate gastroesophageal reflux (GER), this observation does not equate to GERD. Fluoroscopy time should not be prolonged to attempt to demonstrate GER during barium contrast radiography. There are no data to justify prolonging fluoroscopy time to perform provocative maneuvers to demonstrate reflux during barium contrast UGI series. Symptoms of GERD may be associated with physiologic esophageal acid exposure measured by intraesophageal pH monitoring, and a significant percentage of patients with abnormal esophageal acid exposure have no or minimal clinical symptoms of reflux. Abnormal acid exposure defined by pH monitoring over a 24-h period does not equate to GERD. In clinical practice presumptive diagnosis of GERD is reasonably assumed by substantial reduction or elimination of suspected reflux symptoms during therapeutic trial of acid reduction therapy
A Systematic Approach to Multiple Breath Nitrogen Washout Test Quality
Background: Accurate estimates of multiple breath washout (MBW) outcomes require correct operation of the device, appropriate distraction of the subject to ensure they breathe in a manner representative of their relaxed tidal breathing pattern, and appropriate interpretation of the acquired data. Based on available recommendations for an acceptable MBW test, we aimed to develop a protocol to systematically evaluate MBW measurements based on these criteria. Methods: 50MBWtest occasions were systematically reviewed for technical elements and whether the breathing pattern was representative of relaxed tidal breathing by an experienced MBW operator. The impact of qualitative and quantitative criteria on inter-observer agreement was assessed across eight MBW operators (n = 20 test occasions, compared using a Kappa statistic). Results: Using qualitative criteria, 46/168 trials were rejected: 16.6%were technically unacceptable and 10.7% were excluded due to inappropriate breathing pattern. Reviewer agreement was good using qualitative criteria and further improved with quantitative criteria from (κ = 0.53– 0.83%) to (κ 0.73–0.97%), but at the cost of exclusion of further test occasions in this retrospective data analysis. Conclusions: The application of the systematic review improved inter-observer agreement but did not affect reported MBW outcomes
Evaluation of two dairy herd reproductive performance indicators that are adjusted for voluntary waiting period
<p>Abstract</p> <p>Background</p> <p>Overall reproductive performance of dairy herds is monitored by various indicators. Most of them do not consider all eligible animals and do not consider different management strategies at farm level. This problem can be alleviated by measuring the proportion of pregnant cows by specific intervals after their calving date or after a fixed time period, such as the voluntary waiting period. The aim of this study was to evaluate two reproductive performance indicators that consider the voluntary waiting period at the herd. The two indicators were: percentage of pregnant cows in the herd after the voluntary waiting period plus 30 days (PV30) and percentage of inseminated cows in the herd after the voluntary waiting period plus 30 days (IV30). We wanted to assess how PV30 and IV30 perform in a simulation of herds with different reproductive management and physiology and to compare them to indicators of reproductive performance that do not consider the herd voluntary waiting period.</p> <p>Methods</p> <p>To evaluate the reproductive indicators we used the SimHerd-program, a stochastic simulation model, and 18 scenarios were simulated. The scenarios were designed by altering the reproductive management efficiency and the status of reproductive physiology of the herd. Logistic regression models, together with receiver operating characteristics (ROC), were used to examine how well the reproductive performance indicators could discriminate between herds of different levels of reproductive management efficiency or reproductive physiology.</p> <p>Results</p> <p>The logistic regression models with the ROC analysis showed that IV30 was the indicator that best discriminated between different levels of management efficiency followed by PV30, calving interval, 200-days not-in calf-rate (NotIC200), in calf rate at100-days (IC100) and a fertility index. For reproductive physiology the ROC analysis showed that the fertility index was the indicator that best discriminated between different levels, followed by PV30, NotIC200, IC100 and the calving interval. IV30 could not discriminate between the two levels.</p> <p>Conclusion</p> <p>PV30 is the single best performance indicator for estimating the level of both herd management efficiency and reproductive physiology followed by NotIC200 and IC100. This indicates that PV30 could be a potential candidate for inclusion in dairy herd improvement schemes.</p
A Realistic Validation Study of a New Nitrogen Multiple-Breath Washout System
Background
For reliable assessment of ventilation inhomogeneity, multiple-breath washout (MBW) systems should be realistically validated. We describe a new lung model for in vitro validation under physiological conditions and the assessment of a new nitrogen (N2)MBW system.
Methods
The N2MBW setup indirectly measures the N2 fraction (FN2) from main-stream carbon dioxide (CO2) and side-stream oxygen (O2) signals: FN2 = 1−FO2−FCO2−FArgon. For in vitro N2MBW, a double chamber plastic lung model was filled with water, heated to 37°C, and ventilated at various lung volumes, respiratory rates, and FCO2. In vivo N2MBW was undertaken in triplets on two occasions in 30 healthy adults. Primary N2MBW outcome was functional residual capacity (FRC). We assessed in vitro error (√[difference]2) between measured and model FRC (100–4174 mL), and error between tests of in vivo FRC, lung clearance index (LCI), and normalized phase III slope indices (Sacin and Scond).
Results
The model generated 145 FRCs under BTPS conditions and various breathing patterns. Mean (SD) error was 2.3 (1.7)%. In 500 to 4174 mL FRCs, 121 (98%) of FRCs were within 5%. In 100 to 400 mL FRCs, the error was better than 7%. In vivo FRC error between tests was 10.1 (8.2)%. LCI was the most reproducible ventilation inhomogeneity index.
Conclusion
The lung model generates lung volumes under the conditions encountered during clinical MBW testing and enables realistic validation of MBW systems. The new N2MBW system reliably measures lung volumes and delivers reproducible LCI values
Recognition and Alleviation of Pain in Animals
The pain and distress which animals experience as a consequence of their use by man figures prominently in discussions of animal welfare. Some improvements have been made in animal housing and husbandry practices and it is likely that further progress will be made in this field. In comparison, relatively little attention has been given to the problem of minimizing the pain and distress caused to animals by the various procedures to which they are subjected. The most publicized of these are the wide range of experimental techniques which are undertaken using laboratory animals, but also includes procedures such as castration of farm animals and neutering operations carried out on pet animals. The prevention or alleviation of the pain associated with such procedures is a complex problem with no single, simple solution. Consideration must be given to the use of analgesic drugs, the provision of high standards of general care, and the use of special nursing techniques. When dealing with post-operative care, the pre-operative management ofthe animal, the operative procedures and the anesthetic regime must all be evaluated and, when necessary, modified to minimize pain or discomfort
Sequential analysis of surfactant, lung function and inflammation in cystic fibrosis patients
BACKGROUND: In a cross-sectional analysis of cystic fibrosis (CF) patients with mild lung disease, reduced surfactant activity was correlated to increased neutrophilic airway inflammation, but not to lung function. So far, longitudinal measurements of surfactant function in CF patients are lacking and it remains unclear how these alterations relate to the progression of airway inflammation as well as decline in pulmonary function over time. METHODS: As part of the BEAT trial, a longitudinal study to assess the course of airway inflammation in CF, we studied lung function, surfactant function and endobronchial inflammation using bronchoalveolar lavage fluid from 20 CF patients with normal pulmonary function (median FEV(1 )94% of predicted) at three times over a three year period. RESULTS: There was a progressive loss of surfactant function, assessed as minimal surface tension. The decline in surfactant function was negatively correlated to an increase in neutrophilic inflammation and a decrease in lung function, assessed by FEV(1), MEF(75/25%VC), and MEF(25%VC). The concentrations of the surfactant specific proteins A, C and D did not change, whereas SP-B increased during this time period. CONCLUSION: Our findings suggest a link between loss of surfactant function driven by progressive airway inflammation and loss of small airway function in CF patients with limited lung disease
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