The feasibility of wireless capsule endoscopy in detecting small intestinal pathology in children under the age of 8 years: a multicentre European study.

Objective: To systematically evaluate the feasibility and methodology to carry out wireless capsule endoscopy (WCE) in children <8 years to define small intestinal pathology. Design: Prospective European multicentre study with negative prior investigation. Patients and interventions: 83 children aged 1.5–7.9 years were recruited. Initially, all were offered “swallowing” (Group 1) for capsule introduction. If this failed endoscopic placement (Group 2) was used and the Roth net, Advance or custom-made introducers were compared. Outcome measures: Primary endpoint: to determine pathology; secondary endpoint: comparison of capsule introduction methods. Results: Capsule introduction: 20 (24%) children aged 4.0–7.9 years (mean, 6.9 years; 14 male) comprising Group 1 were older (p<0.025) than 63 (76%) aged 1.5–7.9 years (mean, 5.25 years; 30 male) forming Group 2. Complications: Roth net mucosal trauma in 50%; no others occurred. The available recording apparatus was inappropriate for those <3 years. Indications: gastrointestinal bleeding: n = 30 (16 positive findings: four ulcerative jejunitis, four polyps, two angiodysplasia, two blue rubber blebs, two Meckel’s diverticula, one anastomotic ulcer, one reduplication); suspected Crohn’s disease: n = 20 (11 had Crohn’s disease); abdominal pain: n = 12 (six positive findings: three Crohn’s disease, two lymphonodular hyperplasia, one blue rubber bleb); protein loss: n = 9 (four lymphangectasia); malabsorption: n = 12 (seven positive findings: six enteropathy, one ascaris). No abnormalities overall: 45%. Conclusion: WCE is feasible and safe down to the age of 1.5 years. 20 children >4 years swallowed the capsule. The Advance introducer proved superior for endoscopic placement. The pathologies encountered showed age specificity and, unlike in adolescents, obscure gastrointestinal bleeding was the commonest indication

The ability of the corneal shape to adapt to acclimatisation with and without soft lenses during a change of altitude

Changes in corneal shape at altitude have not been the subject of research, but are relevant to mountaineers. Chapters 1 and 2 of this thesis review the literature of the anatomy and physiology of the cornea, and factors affecting corneal physiology. Among these factors, and of particular relevance to mountaineers, is that the oxygen concentration in the atmosphere is reduced at high altitude and could contribute to corneal oedema and corneal shape change. When the cornea is subjected to reduced oxygen levels at low altitude there is no consensus as to the level of oxygen which leads to corneal oedema, but some researchers have found the critical oxygen level to be sufficiently high to lend support to the anecdotal reports from high altitude mountaineers that reduced visual acuity does occur at high altitudes (e.g. the summit of Mt. Everest), presumably as a result of corneal oedema. However, there are no reports in the literature that ascending to an altitude of 15 000 ft has any influence on visual acuity. It appears that light scatter induced by a possible oedematous reaction of the cornea to hypoxia at altitudes of up to 15 000 ft is not sufficient to have any influence on visual acuity. Other influential factors apart from low oxygen levels, such as low humidity, low temperature, and interactions between the meteorological factors described as weather, could also have an influence on corneal shape change. A low pressure chamber is an ideal instrument to test each influential factor while other factors are kept constant, however the weather can not be simulated unless experiments are carried out under the natural conditions experienced in the real world. The hypothesis to be tested in the experimental work described in this thesis is that “the cornea is able to adapt to changing conditions and exhibits no significant change in the corneal shape up to 16,400 ft.” Measurements were taken during a high-altitude trek in Nepal and the equipment used and its validation is described in Chapter 3 for measurements of air pressure, altitude, temperature, and humidity. Calibrations against a suitable gold standard and/or manufacturers’ tolerances were undertaken and found to be satisfactory for all instruments to be taken on the trek. A lack of repeatability and validity for the Tono-Pen® XL tonometer had to be accepted because, for safety reasons, IOP had to be measured from the sclera on the trek. There is evidence to suggest that the Tono-Pen manufacturer’s conversion table to convert from measurements taken from the sclera at the limbus rather than from the cornea may be inaccurate. Details are given of the method for measuring corneal shape using an Oculus keratographer, whose output was converted into combined variables consisting of Zemike polynomials and an ellipsoid. A residual rms value was generated from the Zemicke polynomials and was used to describe corneal shape change. Repeatability of the residual rms measurements was not as good as anticipated. However, it was comparable between the two keratographers tested and the variability was regarded as acceptable. The research detailed in this thesis investigates corneal shape change in 11 normal subjects, aged 35 to 54 years, over a period of four days at low altitude (Chapter 4) and in 9 normal subjects, aged 45 to 60 years, on a three week high-altitude trekking tour of Nepal, which reached an altitude of 16,400 feet (Chapter 6). In both studies, measurements were taken three times each day (morning, noon, and evening). Both samples included three subjects who wore soft contact lenses, to investigate if any aspect of corneal shape change was different among contact lens wearers. For all contact lens wearers, the fit and comfort of the lenses were checked during an examination of both the anterior and posterior eye. For the low altitude study (Chapter 4) descriptive statistics reveal a slight tendency for residual rms values to be higher in the small sample of contact lens wearers. No significant corneal shape change with time of day was detected for either the non contact lens wearer category (p = 0.808) or for the contact lens wearer category (p = 0.210). No significant change in corneal shape was found over four days for either the non contact lens wearer category (p = 0.62, p = 0.32, p = 0.11) or for the contact lens wearer category (p = 0.11, p = 0.09, p = 0.35) for morning, noon or evening tests respectively. Chapter 5 describes the complex logistics of the trek, which was organised by the author to allow the battery of tests to be completed at high altitude. In the high altitude study (Chapter 6), residual rms values were analysed with the data categorised according to 5 altitude levels (altitude samples). Descriptive statistics generally show higher sample mean residual rms values at high altitude, greater maximum residual rms values at high altitude, and greater residual rms values in the contact lens wearers. There are statistically significant increases in residual rms values with altitude, identified by ANOVA testing, for both non contact lens wearers (p = 0.0061) and contact lens wearers (p = 0.0002) for their evening tests. The low altitude reference sample l(up to 3,280ft) had a statistically significantly lower mean residual rms value than samples 2 (3,280 to 6,560ft) and 5 (above 13,120 ft) for both contact lens wearers and non wearers, and sample 1 mean was also statistically significantly lower than sample 4 (9,840ft to 13,120ft) for the non wearers. The meteorological data revealed a very stable weather situation throughout the entire testing phase of the trek. For each eye tested there was very little or no evidence for any linear association between residual rms and humidity (rmean = 0.24), air pressure (rmean = 0.18), temperature (rmean = 0.20), or altitude (rmean = 0.19). Transient retinal vasculature changes occurred in two subjects. The degree of contact lens movement increased for all three subjects during the trek. The z-value, the distance between the highest and deepest point of the corneal shape described by the Zemike coefficients, was analysed at both low and high altitude for each subject. There is a tendency for the mean z-values for contact lens wearers to be higher than those of the non contact lens wearers at both low and high altitude. The findings from this study suggest that contact lens wear causes an increase in z-values irrespective of altitude. There is also a tendency for a greater range of z-values to be found in contact lens wearers. The risk of contact lens wear inducing irritations rises dramatically when movement of the contact lens is influenced by a very variable z-value. This elevated range of z-values at high altitude should undoubtedly be taken into consideration during lens fitting for mountaineers who wish to ascend to high altitudes. The conclusions of this thesis should be interpreted with caution, due to the small samples; however the hypothesis is rejected for the evening measurements. The corneal shape changes detailed in this thesis are likely to be the result of a combination of a reduced oxygen partial pressure at high altitudes, possibly exacerbated by fatigue, and, for contact lens wearers, the effects of the contact lens on the cornea. Unfortunately, there was limited time available to complete the battery of tests at altitude and limited electrical power on the trek. These factors limited the number and range of tests that could be carried out, and as a result no measurements of visual function with altitude were included in the study

Self-consistent Wigner distribution function study of gate-voltage controlled triple-barrier resonant tunnelling diode

The electron transport through the triple-barrier resonant tunnelling diode (TBRTD) have been studied by the self-consistent numerical method for the Wigner-Poisson problem. The electron flow through the TBRTD can be controlled by the gate voltage applied to one of the potential well regions. For different gate voltage values we have determined the current-voltage characteristics, potential energy profiles, and electron density distribution. We have found the enhancement of the peak-to-valley ratio (up to $\sim$10), the appearance of the linear current versus bias voltage behaviour within the negative-differential resistance region, and the bistability of the current-voltage characteristics. The analysis of the self-consistent potential energy profiles and electron density distribution allowed us to provide a physical interpretation of these properties.Comment: 13 pages, 7 figure

Ultrafast carrier relaxation and vertical-transport phenomena in semiconductor superlattices: A Monte Carlo analysis

The ultrafast dynamics of photoexcited carriers in semiconductor superlattices is studied theoretically on the basis of a Monte Carlo solution of the coupled Boltzmann transport equations for electrons and holes. The approach allows a kinetic description of the relevant interaction mechanisms such as intra- miniband and interminiband carrier-phonon scattering processes. The energy relaxation of photoexcited carriers, as well as their vertical transport, is investigated in detail. The effects of the multiminiband nature of the superlattice spectrum on the energy relaxation process are discussed with particular emphasis on the presence of Bloch oscillations induced by an external electric field. The analysis is performed for different superlattice structures and excitation conditions. It shows the dominant role of carrier-polar-optical-phonon interaction in determining the nature of the carrier dynamics in the low-density limit. In particular, the miniband width, compared to the phonon energy, turns out to be a relevant quantity in predicting the existence of Bloch oscillations

Electrical activity-triggered glucagon-like peptide-1 secretion from primary murine L-cells

Glucagon like peptide 1 (GLP-1) based therapies are now widely used for the treatment of type 2 diabetes. Developing our understanding of intestinal GLP-1 release may facilitate the development of new therapeutics aimed at targeting the GLP-1 producing L-cells. This study was undertaken to characterise the electrical activity of primary L-cells and the importance of voltage gated sodium and calcium channels for GLP-1 secretion. Primary murine L-cells were identified and purified using transgenic mice expressing a fluorescent protein driven by the proglucagon promoter. Fluorescent L-cells were identified within primary colonic cultures for patch clamp recordings. GLP-1 secretion was measured from primary colonic cultures. L-cells purified by flow cytometry were used to measure gene expression by microarray and quantitative RT-PCR. Electrical activity in L-cells was due to large voltage gated sodium currents, inhibition of which by tetrodotoxin reduced both basal and glutamine-stimulated GLP-1 secretion. Voltage gated calcium channels were predominantly of the L-type, Q-type and T-type, by expression analysis, consistent with the finding that GLP-1 release was blocked both by nifedipine and ω-conotoxin MVIIC. We observed large voltage-dependent potassium currents, but only a small chromanol sensitive current that might be attributable to KCNQ1. GLP-1 release from primary L-cells is linked to electrical activity and activation of L-type and Q-type calcium currents. The concept of an electrically excitable L-cell provides a basis for understanding how GLP-1 release may be modulated by nutrient, hormonal and pharmaceutical stimuli

Expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases

<p>Abstract</p> <p>Background</p> <p>Inflammatory lung diseases are a major morbidity factor in children. Therefore, novel strategies for early detection of inflammatory lung diseases are of high interest. Bacterial lipopolysaccharide (LPS) is recognized via Toll-like receptors and CD14. CD14 exists as a soluble (sCD14) and membrane-associated (mCD14) protein, present on the surface of leukocytes. Previous studies suggest sCD14 as potential marker for inflammatory diseases, but their potential role in pediatric lung diseases remained elusive. Therefore, we examined the expression, regulation and significance of sCD14 and mCD14 in pediatric lung diseases.</p> <p>Methods</p> <p>sCD14 levels were quantified in serum and bronchoalveolar lavage fluid (BALF) of children with infective (pneumonia, cystic fibrosis, CF) and non-infective (asthma) inflammatory lung diseases and healthy control subjects by ELISA. Membrane CD14 expression levels on monocytes in peripheral blood and on alveolar macrophages in BALF were quantified by flow cytometry. <it>In vitro </it>studies were performed to investigate which factors regulate sCD14 release and mCD14 expression.</p> <p>Results</p> <p>sCD14 serum levels were specifically increased in serum of children with pneumonia compared to CF, asthma and control subjects. <it>In vitro</it>, CpG induced the release of sCD14 levels in a protease-independent manner, whereas LPS-mediated mCD14 shedding was prevented by serine protease inhibition.</p> <p>Conclusions</p> <p>This study demonstrates for the first time the expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases and suggests sCD14 as potential marker for pneumonia in children.</p

Expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases

<p>Abstract</p> <p>Background</p> <p>Inflammatory lung diseases are a major morbidity factor in children. Therefore, novel strategies for early detection of inflammatory lung diseases are of high interest. Bacterial lipopolysaccharide (LPS) is recognized via Toll-like receptors and CD14. CD14 exists as a soluble (sCD14) and membrane-associated (mCD14) protein, present on the surface of leukocytes. Previous studies suggest sCD14 as potential marker for inflammatory diseases, but their potential role in pediatric lung diseases remained elusive. Therefore, we examined the expression, regulation and significance of sCD14 and mCD14 in pediatric lung diseases.</p> <p>Methods</p> <p>sCD14 levels were quantified in serum and bronchoalveolar lavage fluid (BALF) of children with infective (pneumonia, cystic fibrosis, CF) and non-infective (asthma) inflammatory lung diseases and healthy control subjects by ELISA. Membrane CD14 expression levels on monocytes in peripheral blood and on alveolar macrophages in BALF were quantified by flow cytometry. <it>In vitro </it>studies were performed to investigate which factors regulate sCD14 release and mCD14 expression.</p> <p>Results</p> <p>sCD14 serum levels were specifically increased in serum of children with pneumonia compared to CF, asthma and control subjects. <it>In vitro</it>, CpG induced the release of sCD14 levels in a protease-independent manner, whereas LPS-mediated mCD14 shedding was prevented by serine protease inhibition.</p> <p>Conclusions</p> <p>This study demonstrates for the first time the expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases and suggests sCD14 as potential marker for pneumonia in children.</p