The effect of haem limitation and iron restriction on outer membrane proteins and on respiratory systems of non typable Haemophilus influenzae

The effects of haem limitation and iron restriction on cells of non typable Haemophilus influenzae were investigated. Haem limitation was achieved by adding concentrations of haem to growth media which resulted in substantial decreases in final cell yields. Iron restriction was achieved by substituting protoporphyrin IX (PPIX) for haem in the growth medium and adding an iron chelator to the system. The effect of these nutrient limitations on a) outer membrane composition, and b) respiratory systems of non typable H.influenzae was investigated. Several of the strains examined produced new PPIX-specific outer membrane proteins when cultured utilising PPIX as a porphyrin source. The immune response of patients with bronchiectasis to outer membrane antigens of H.influenzae cultured under iron-restricted conditions was analysed by ELISA and immunoblotting techniques. ELISA analysis revealed that individuals with severe bronchiectasis had high titres of antibodies directed against H.influenzae OMs in both serum and sputum. Immunoblotting with homologous serum showed that where PPIX-specific OMPs were produced they were antigenic and were recognised by patients' serum. This suggested that these H.influenzae OMPs may be expressed in vivo. Additionally, the development of the immune responses to non typable H.influenzae outer membrane antigens was investigated using a rat lung model. Bacteria encased in agar beads were inoculated intratracheally into rat lungs, infection was established, and the immune response monitored for 6 weeks. The animals developed antibodies to PPIX-specific OMPs during the course of infection, providing further evidence that H.influenzae express these novel OMP antigens when growing in vivo. Studies in vitro on respiratory systems of phenotypically altered H.influenzae showed that bacteria grown utilising PPIX as a porphyrin source, or under conditions of iron-restriction produced ten fold fewer cytochromes than cells grown in nutrient excess, while haem limited H.influenzae produced no detectable cytochromes. Respiration of various substrates was depressed in haem limited and in PPIX-grown cultures as compared with cells grown in nutrient excess.

Non-invasive respiratory monitoring using long-period fiber grating sensors

In non-invasive ventilation, continuous monitoring of respiratory volumes is essential. Here, we present a method for the measurement of respiratory volumes by a single fiber-grating sensor of bending and provide the proof-of-principle by applying a calibration-test measurement procedure on a set of 18 healthy volunteers. Results establish a linear correlation between a change in lung volume and the corresponding change in a local thorax curvature. They also show good sensor accuracy in measurements of tidal and minute respiratory volumes for different types of breathing. The proposed technique does not rely on the air flow through an oronasal mask or the observation of chest movement by a clinician, which distinguishes it from the current clinical practice. © 2014 Optical Society of America.

A three dimensional surface measurement and reconstruction system for respiratory function analysis

Respiration is a complex activity. If the relationship between all neurological and skeletomuscular interactions was perfectly understood, an accurate dynamic model of the respiratory system could be developed and the interaction between different inputs and outputs could be investigated in a straightforward fashion. Unfortunately, this is not the case and does not appear to be viable at this time. In addition, the provision of appropriate sensor signals for such a model would be a considerable invasive task. Useful quantitative information with respect to respiratory performance can be gained from non-invasive monitoring of chest and abdomen motion. Currently available devices are not well suited in application for spirometric measurement for ambulatory monitoring. A sensor matrix measurement technique is investigated to identify suitable sensing elements with which to base an upper body surface measurement device that monitors respiration. This thesis is divided into two main areas of investigation; model based and geometrical based surface plethysmography. In the first instance, chapter 2 deals with an array of tactile sensors that are used as progression of existing and previously investigated volumetric measurement schemes based on models of respiration. Chapter 3 details a non-model based geometrical approach to surface (and hence volumetric) profile measurement. Later sections of the thesis concentrate upon the development of a functioning prototype sensor array. To broaden the application area the study has been conducted as it would be fore a generically configured sensor array. In experimental form the system performance on group estimation compares favourably with existing system on volumetric performance. In addition provides continuous transient measurement of respiratory motion within an acceptable accuracy using approximately 20 sensing elements. Because of the potential size and complexity of the system it is possible to deploy it as a fully mobile ambulatory monitoring device, which may be used outside of the laboratory. It provides a means by which to isolate coupled physiological functions and thus allows individual contributions to be analysed separately. Thus facilitating greater understanding of respiratory physiology and diagnostic capabilities. The outcome of the study is the basis for a three-dimensional surface contour sensing system that is suitable for respiratory function monitoring and has the prospect with future development to be incorporated into a garment based clinical tool.

Medicines non-use in primary care

This study expands the current knowledge base on the nature, causes and fate of unused medicines in primary care. Three methodologies were used and participants for each element were sampled from the population of Eastern Birmingham PCT. A detailed assessment was made of medicines returned to pharmacies and GP surgeries for destruction and a postal questionnaire covering medicines use and disposal was used to patients randomly selected from the electoral roll. The content of this questionnaire was informed by qualitative data from a group interview on the subject. By use of these three methods it was possible to triangulate the data, providing a comprehensive assessment of unused medicines. Unused medicines were found to be ubiquitous in primary care and cardiovascular, diabetic and respiratory medicines are unused in substantial quantities, accounting for a considerable proportion of the total financial value of all unused medicines. Additionally, analgesic and psychoactive medicines were highlighted as being unused in sufficient quantities for concern. Anti-infective medicines also appear to be present and unused in a substantial proportion of patients’ homes. Changes to prescribed therapy and non-compliance were identified as important factors leading to the generation of unused medicines. However, a wide array of other elements influence the quantities and types of medicines that are unused including the concordancy of GP consultations and medication reviews and patient factors such as age, sex or ethnicity. Medicines were appropriately discarded by 1 in 3 patients through return to a medical or pharmaceutical establishment. Inappropriate disposal was by placing in household refuse or through grey and black water with the possibility of hoarding or diversion also being identified. No correlations wre found between the weight of unused medicines and any clinical or financial factor. The study has highlighted unused medicines to be an issue of some concern and one that requires further study.