Inhalational therapy is used to deliver medication to the lung, either to treat diseases or, less commonly, for systemic absorption. A number of devices have been developed to aid or improve inhalational therapy, and this thesis deals with metered dose inhalers, used with spacer devices, and nebulisers. Despite their seemingly simple construction and concept, the correct choice and use of an inhalational drug delivery device can dramatically alter the amount of drug available for inhalation. Studies in this thesis, supported by emerging pharmacokinetic evidence, have highlighted areas where the device can affect the drug delivery. In vitro methods were used to quantify and characterise the different devices, including inertial impaction for aerosol particle sizing, sinus flow pumps for breathing simulation and high speed video recordings to analyse aerosol plume geometry and spacer function. The results these studies reveal a number of factors that may affect drug delivery. Firstly, delay between metered dose inhaler actuation into a spacer and inhalation can reduce the amount of drug available to the patient. Secondly, multiple actuations of the metered dose inhaler into the spacer prior to inhalation also reduce the amount of drug available. The size of the spacer may also affect the amount of drug available for inhalation, and this will vary with the drug prescribed. Different formulations may differ in their aerosol cloud speed and volume, and this may alter the amount of drug delivered from different spacers. Plastic and polycarbonate spacers may be highly charged with static electricity. Such spacers deliver less drug than those where the static charge has been reduced by an anti-static lining, or where the spacer is constructed from static dissipative materials. Washing the spacer also reduces its charge, but the optimum washing regime for spacers is not known. Different nebulisers deliver different amounts of drug, and the assessment of nebulisers varies with the method used. Accurate assessment should include direct measurement of the mass of drug released, and should incorporate simulated patient breathing. Effective nebulisation of drug ends after a few minutes. This time will depend on the nebuliser and drug being used, but for some medications administered for asthma, little drug may be delivered after five minutes, and patients should be advised to stop nebulisation after this time. In conclusion, studies in this thesis support the hypothesis that the method of use or choice of inhalational drug delivery device affects the amount of drug that is available for inhalation by the patient.

Introduction: Conventional radiotherapy efficacy is hampered by inefficient dose delivery to the target and normal tissue toxicity. Thus the use of more targeted radiotherapeutic tools such as targeted radionuclide therapy utilising for example 131I conjugated to metaiodobenzylguanidine (MIBG) is a more effective approach. Additionally, the development of new radiosensitising compounds is also at the forefront of cancer research. Mirin, an MRN complex inhibitor, and Olaparib, a PARP-1 inhibitor, are two such compounds that have been predicted to enhance radiotherapy Aims: The aims of the present study were to determine the radiosensitising potential of Mirin and Olaparib in combination with X-ray radiation and [131I]MIBG in vitro and interrogate the molecular mechanisms underpinning the cellular response to combination treatments. Results: Despite both X-ray radiation and [131I]MIBG eliciting a dose dependent reduction in cell survival, the pattern of activation of DNA repair proteins including ATM kinase, γ-H2AX and RAD51 varied greatly, demonstrating that the dynamics of DNA damage and repair, was much more prolonged with [131I]MIBG with respect to activation of DNA repair pathway components. There was also a variation in cells response to the two radiation qualities in combination with Mirin and Olaparib, with Mirin showing no radiosensitising effect with X-rays, however, significant radiosensitisation was observed in those exposed to Mirin and [131I]MIBG. Olaparib demonstrated effective radiosensitising potential when combined with both X-ray radiation and [131I]MIBG despite the difference in duration of DNA damaging effects. Conclusions: The radiosensitising potential of Mirin was dependant on radiation quality with a greater radiosensitisation seen with [131I]MIBG over X-irradiation. Conversely, Olaparib exerted tumour cell radiosensitisation regardless of radiation type. Additionally, mechanistic analyses indicated that Mirin is acting to efficiently inhibit the MRN-ATM directed DNA repair pathway in both cases therefore the lack of radiosensitisation produced with X-ray radiation is possibly as a result of residual or compensatory DNA repair.

Antibiotic resistance is an ever increasing threat to global health which is worsened by the lack of viable alternatives to antibiotics. Photodynamic Therapy (PDT) involves the application of light, a sensitiser and molecular oxygen to generate cytotoxic radicals at a specific target and can be used in the treatment of both cancers and bacterial infections. The main limitation of PDT is the lack of penetration of light through tissue restricting PDT to superficial cancers and infections. Sonodynamic Therapy (SDT) is an emerging technique used in the treatment of cancer and involves the targeted generation of cytotoxic radicals through the application of ultrasound in the presence of a sensitiser and molecular oxygen. The advantage of using ultrasound is the ability to target deeper seated infections as it can penetrate further through tissue. Recent studies have indicated that SDT has the potential to be used in the treatment of bacterial infections. In this thesis, antimicrobial SDT will be investigated as a potential treatment for bacterial infections. Chapter 2 includes the methods and materials used in each of the three chapters. The first results chapter (Chapter 3) investigates a range of different sensitisers for their potential use in antimicrobial SDT and establishes ultrasound parameters to optimise treatment in Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. The antimicrobial SDT efficacy of the sensitisers were compared with their physiochemical properties to determine if any structure-activity relationship was evident. The results generated in this chapter demonstrated that the Gram-negative P. aeruginosa was less susceptible to the treatment than the Gram-positive 5. aureus. Of the sensitisers that were examined, Rose Bengal and Protoporphyrin IX were the best performers. While no unambiguous relationship was established between the structure of the sensitisers and their antimicrobial efficacy, there was a slight trend between the LogD of the sensitisers and their antimicrobial efficacy. These findings indicated that uptake of the sensitisers was a more important factor than the degree of cytotoxic radical generation. The second results chapter (Chapter 4) expanded upon the findings from Chapter 3 and involved the synthesis of a Rose Bengal-peptide conjugate that aimed to increase the efficacy of SDT in P. aeruginosa. It was observed that the conjugation of the peptide increased the uptake of Rose Bengal in P. aeruginosa and S. aureus which also coincided with a significant increase in the effectiveness of the SDT treatment towards P. aeruginosa. A pilot in vivo study also indicated that antimicrobial SDT may be an effective treatment for localised bacterial infections. The third results chapter (Chapter 5) investigated the potential of a combined antimicrobial near infrared (NIR) PDT / SDT treatment using newly synthesised iodinated cyanine dye- based sensitisers. Minimal reductions in bacterial viability were observed when using SDT with larger reductions observed using NIR PDT with the exception of P. aeruginosa which showed little to no response to PDT treatment. Simultaneous treatment of S. aureus with PDT and SDT proved very effective in clearing the bacterial population, however P. aeruginosa remained unresponsive to the combined treatment. Chapter 6 summarises the conclusions and provides an outlook for future work.

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Health literacy represents the cognitive and social skills which determine the motivation and ability of individuals to gain access to, understand and use information in ways which promote and maintain good health (Nutbeam and World Health 1998:10). To date, there is a paucity of research looking at health literacy in terms of specific types of Complementary and Alternative Medicine (CAM) use. However, levels of current usage of CAM with their emphasis on raising awareness about health and healing suggest that they may be an acceptable and useful way to help people to manage their health and wellbeing. Reiki can be learned by anyone and, once a person has learned it, he or she is encouraged to regularly use Reiki on themselves as a means of self-care. This research address the question; how does learning and self-use of Reiki enhance health literacy? The starting point of this multi-stage qualitative project was the formation of a theoretical model of Reiki health literacy based on a critical review of the Reiki and health literacy literature. The model was refined using unstructured interviews with a purposive sample of 10 Reiki Master Teachers and further explored in semi-structured interviews with 25 Reiki level one and two practitioners who regularly self use Reiki. Analysis of the data indicated that participants perceived Reiki as an ‘easy’ skill to learn and valuable to use on a regular basis. Such self-use helped them make changes to their lifestyle, including diet and ways they coped at work. Reiki was used pro-actively to prevent ill-health and maintain good physical and emotional health. Participants spoke of using their Reiki knowledge and skills to self-treat minor physical ailments (headaches, muscular pains) and to manage mental and emotional problems such as worry, stress and anxiety. This research develops, refines and applies a novel model of Reiki health literacy and in doing so provides supportive evidence of the potential of learning Reiki and its regular self-use to enable a pro-active approach to health and well-being. Implications of this research include the use of Reiki as a supportive intervention for enhancing health literacy. Because anyone can learn and practise self-use of Reiki it may be a useful intervention for enhancing the health literacy skills of disadvantaged populations who are least likely to have highly developed health literacy skills. The research adds to the limited evidence base on self-use of Reiki and deepens understanding of the benefits of Reiki.

The goal of the thesis was to investigate, and better define, what the requirements are for accurate small field relative dosimetry. Diode detector selection and experimental techniques were evaluated. EGSnrc Monte Carlo simulations were used to predict diode detector dosimetric parameters and assist in interpreting measured data. An emerging scintillator based detector technology was also tested and methods developed to standardize the reporting of small field dosimetric data. Using careful experimental methods the relative output uncertainty for the smallest square field size of side 0.5 cm was reduced to better than ±1.00% for all detector types. Monte Carlo simulation data revealed that for the same small field size the relative output measured using unshielded and shielded diodes will be 5% and 10% greater than the actual relative output in water. Further simulation work showed that simplified diode detector models are valid for use in small field dosimetry simulations. The diode detector over-response was also shown to be insensitive to variations in the electron energy and spot size incident on the Bremsstrahlung target. Experimental methods were refined to include the definition of an effective field size, which was shown to remove much of the ambiguity in reporting small field relative output data across a population of linear accelerators. Each of the for mentioned areas of investigation have been shown to be requirements for accurate small field relative.

No description available.

No description available.