Background: Despite public health campaigns and improvements in healthcare, socioeconomic gradients in health and life expectancy persist, and in many cases are becoming more marked – the gradient in coronary heart disease being a prime example. Classic cardiovascular risk factors (e.g. smoking, cholesterol and blood pressure) only partially explain the deprivation effect, and attempts to narrow the health gap by focussing on such risk factors do not appear to be succeeding. There also appear to be socioeconomic differences in uptake of healthy lifestyle advice. The work described in this thesis aimed to expand current understanding of the deprivation-based gap in health and life expectancy, focussing particularly on the socioeconomic gradient in cardiovascular risk. Methods: Using a cross-sectional, population-based study design based in the Greater Glasgow area, 666 participants were selected on the basis of area-level social deprivation (Scottish Index for Multiple Deprivation ranking). The study was designed to include approximately equal numbers from most deprived and least deprived areas; equal numbers of male and female participants and equal numbers of participants from each age group studied (35-44; 45-54 and 55-64 years). Participants completed an extensive questionnaire on health, lifestyle and early life experiences. Anthropometric measures (height, leg length, weight, waist, hip and thigh circumferences) were recorded. Blood pressure, heart rate and parameters of lung function (Forced Expiratory Volume in 1 second [FEV1] and Forced Vital Capacity [FVC]) were recorded. Psychological assessments (General Health Questionnaire-28, Generalised Self-Efficacy Scale, Sense of Coherence Scale, Beck Hopelessness Scale, Eysenck Personality Scale and Rosenberg Self-Esteem Scale) and assessments of cognitive function (Auditory Verbal Learning Test, Choice Reaction Time and Stroop Test) were undertaken. Fasting blood samples were obtained for classic and emerging cardiovascular risk factors including lipid profile, glucose, insulin, leptin, adiponectin, C-reactive protein, interleukin-6, soluble intercellular adhesion molecule-1, von Willebrand Factor, fibrinogen, D-dimer and tissue plasminogen activator antigen. Carotid ultrasound assessment of intima-media thickness (cIMT), plaque score and arterial stiffness was performed. Results: Total and low density lipoprotein cholesterol were significantly higher in the least deprived group (both p<0.0001). Triglycerides were higher and high density lipoprotein cholesterol lower in the most deprived group (both p<0.0001). Fasting glucose, insulin and leptin were higher in the most deprived group. C-reactive protein, interleukin-6 and soluble intercellular adhesion molecule-1 were higher in the most deprived group (all p<0.0001). Von Willebrand factor, fibrinogen and D-dimer were higher in the most deprived group. Age- and sex-adjusted cIMT was significantly higher in the most deprived group, but on subgroup analysis this difference was only apparent in the highest age tertile in males (>56.3 years). Plaque score showed a much more highly significant deprivation difference in the group as a whole (p<0.0001). No differences in parameters of arterial stiffness were found between the most deprived and least deprived groups. Neither adjustment for classic nor emerging cardiovascular risk factors, either alone or in combination, abolished the area-level deprivation-based difference in plaque presence or cIMT. Adjustment for early life markers of socioeconomic status in addition to classic cardiovascular risk factors abolished the deprivation-based difference in plaque presence. Further associations between early life factors and health outcomes were noted: lung function (FEV1) and cognitive performance appeared to be influenced by father’s occupation, whether the parents/guardians were owner-occupiers or tenants, and by degree of overcrowding; cIMT was modestly related to father’s occupation and carotid plaque was related strongly to father’s occupation and parental home status. Socioeconomic differences were noted in the impact of personality in determining mental wellbeing, and also in relation to the health behaviours of fruit and vegetable consumption and smoking cessation. Conclusions: The relationship between social deprivation and health is complex and multifactorial and appears to involve the interplay of early life factors, biological mediators, psychological parameters such as personality and cognitive function, health behaviours and outcomes such as atherosclerosis. Approaches aiming to narrow the deprivation gap in health will need to be designed to take into account this complexity, addressing factors such as early life experiences and personality, as well as the more classically recognised factors such as smoking, cholesterol and blood pressure, if they are to have a chance of succeeding in improving the health of those most in need.

Background: Single-handed practice, a traditional model of general practice, has been an important facet of primary care provision since before the establishment of the National Health Service in 1948, but has increasingly been challenged by the growth of large practices. Now less than 10 % of GPs remain single-handed in the UK, concentrated in rural areas and areas of urban deprivation. This gradual decline of single-handed practice has resulted partly from the continued advocacy of partnership by the government, but is also indicative of NHS modernisation itself focusing on the delivery of high quality of care. However, little is known about single-handed GP today, particularly in urban areas, and what impact the most recent policy changes resulting from the implementation of the 2004 General Medical Service contract has had on them. Aim The aim of this thesis is to explore the current position of single-handed practices in urban areas exploring the quality of care delivered and to develop an understanding of how being a single-handed GP affects their practices in today’s NHS. Methods A mixed method methodology was employed. Quantitative analyses of routine datasets described characteristics of single-handed general practitioners and their practice population, and also examined their quality of care in comparison to that of group practices. A set of qualitative interviews were conducted to explore the experiences of a single-handed GP and their views of the future of this type of practice. Results The data presented in this thesis shows that single-handed practice accounted for 12.6% (n=85) of urban Scottish general practices and had over 150,000 registered patients with a high proportion living in areas of socio-economic deprivation. GPs working single-handedly were more likely to be male, older, qualified in South Asia, and had larger personal list size than their counterparts in group practices. Taking account of practice and population characteristics, single-handed practices offered comparable quality of care to large practices but tended to refer more patients with coronary heart disease to secondary care and also attained fewer organisational points in the Quality and Outcomes Framework of the new GP contract than larger practices. The data generated from the GPs interviews shed light on such patterns, suggesting that single-handed practices had little benefit from the economies scale possible in larger practices with regards to employing additional practice staff and sharing tasks within practice teams. Single-handed GPs continued practising on their own as they enjoyed the true levels of autonomy regarding clinical and managerial work within their own practices. However, the increasing accountability associated with the new contract in terms of Quality and Outcomes Framework monitoring may be a greater challenge to their freedom than current Government rhetoric about larger practice configurations. Some, however, had begun to find other ways of supporting themselves, such as sharing facilities with other small practices or using colleagues also from small practices to provide cross-cover when required. Conclusion The findings from the quantitative and qualitative work drawn together in this thesis highlighted that there was a significant group of GPs in urban areas who continue to practice single-handedly, whose quality of care was as good as that provided by larger practices when difference in the socio-economic status of practice populations between practices was taken into account. Although no significant association between practice size and CHD outcome measures (mortality, EMAs, prescribing and operation rates) was observed, there was variation in out-patient referral rates that remained unexplained, suggesting that patient-related factors such as their level of morbidity, may be important. Under the new contract, with little advantage in practice organisation, single-handed practices attained comparable clinical performance to group practices in the Quality and Outcomes Framework, though the underlying distribution of quality scores and percentage achievement for individual indicators in relation to practice size needs to be examined further, incorporating data on exception report to understand the full effect of practice size on QOF attainment. Enjoying their personal autonomy within their own practices, many thought they also provided a good quality of care for their patients, particularly in relation to access and continuity, and would remain as single-handers. However, concerns over the increasing accountability largely associated with the new contract in terms of QOF requirements may be a greater challenge to single-handed practices than current government rhetoric about larger practice configurations. The findings of this study indicates that the quality of care provided single-handed practice is at least as good as and, possibly better than that of larger practices. This has implications for service delivery in general practices, because it suggests that a policy drive to the development of large units in general practice may not necessarily lead to an improvement in quality of care as it intended. Despite some limitations, the importance of socio-economic deprivation rather than practice size in explaining the observed differences in quality outcomes emphasises the need to address health inequalities in populations, as well as the need to support practices such as single-handed practices working in the areas of deprivation and with ethnic minority populations, and to value their ongoing contribution to the provision of primary care in such areas.

Nitrate ingestion leads to high luminal concentrations of nitric oxide being generated where saliva meets gastric acid. Nitric oxide generates N-nitrosative stress on reacting with oxygen at neutral pH. We aimed to ascertain if luminal nitric oxide exerts nitrosative stress in the upper GI tract, and to assess the influence of acid reflux. We utilised a specialised silicone tube as an epithelial model, inserting it into the upper gastro-intestinal tract of humans. Healthy volunteers were studied with and without ingestion of 15N enriched nitrate and Barrett’s oesophagus patients with and without stimulation of reflux. In volunteers, nitrate ingestion resulted in significantly higher concentrations of N-nitrosomorpholine in the tube sections exposed to acid. In Barrett’s patients, generation of N-nitrosomorpholine shifted proximally, with most nitrosative stress occurring within the oesophagus during reflux episodes. This chemistry may be harmful to patients with erosive esophagitis whose epithelium will be more sensitive to chemical mutagenesis.

Introduction: Patients who have been repeatedly removed from General Practice (GP) lists, so-called “revolving door” patients in general practice have not been examined in the literature. This mixed methods study sought to define and characterise “revolving door” patients in general practice in Scotland. It investigated the impact they had on the NHS and the impact this status may have on “revolving door” patients themselves. Methods: Thirteen semi-structured interviews with Practitioner Services and GP professional key informants and one “ex-revolving door” patient were conducted and analysed using a Charmazian grounded theory approach. Patient removal data from the Community Health Index were used to construct cohorts of “revolving door” patients and link them with routine NHS data on hospital admissions, outpatient attendances and drug misuse treatment episodes. These data were analysed quantitatively and qualitatively and all the data were integrated dialectically. Results: “Revolving door” patients were removed four or more times from GP lists in six years. There was a dramatic decline in the number of “revolving door” patients in Scotland whilst the study was conducted. It appeared this was because the NHS response altered due to changes in approaches to treating problem drug use and pressure to reduce removal activity from professional bodies. The final influence was the positive, ethical, regulatory, and financial climate of the 2004 General Medical Services contract. “Revolving door” patients had three necessary characteristics: unreasonable expectations of what the National Health Service had to offer, inappropriate behaviour and unmet health needs. Problem substance use and psychiatric health problems were important. Professionals who came into contact with “revolving door” patients found it a difficult experience and they generated a lot of work. Being a “revolving door” patient impacted on the quality of care that patients received in general practice in terms of relational, informational and management continuity of care. “Revolving door” patients were more likely to be admitted to hospital after they have been removed from a GP list and more likely to be referred for addiction care after they were re-registered. Conclusions: It was the status of being repeatedly removed from GP lists that set “revolving door” patients apart from the usual general practice population. I suggest that GPs were able to suspend their core values and remove “revolving door” patients because the legitimate work of general practice was challenged. There were two ways in which this may happen. The first was that “revolving door” patient’s dominant health needs were not viewed as biomedical because they contained aspects of a moral schema of understanding. The second was that their behaviour or expectations threatened the doctor-patient relationship. These were features common to other patients reviewed in the literature on problem doctor-patient relationships. “Revolving door” patients did not understand the unwritten rules of the doctor-patient relationship; so removing them from GP lists did not change their behaviour. Current theories about personality disorder and adult attachment should be integrated into the work of general practice and further researched in this context. This might help GPs and patients to improve problem doctor-patient relationships.

Stroke accounts for 9% of all deaths worldwide and is a major cause of severe disability (Donnan et al, 2008). Following ischaemic stroke, the penumbra represents tissue which is hypoperfused and functionally impaired but is not yet irreversibly damaged. However, the penumbra has a finite lifespan and will proceed to infarction in the absence of swift reperfusion. Therefore, the identification and potential salvage of penumbral tissue in acute ischaemic stroke is the ultimate goal for both clinicians and experimental stroke researchers. Positron emission tomography (PET) is the ‘gold standard’ imaging modality for identifying the penumbra, but the complex logistics of PET limit its widespread use. Magnetic Resonance Imaging (MRI) is widely used for penumbra imaging in both clinical and pre-clinical research. The MRI perfusion-diffusion mismatch model provides an approximation of the penumbra, where diffusion weighted imaging (DWI) identifies the core of ischaemic injury and perfusion weighted imaging (PWI) reveals the perfusion deficit. The mismatch between the DWI and PWI provides a measure of penumbral tissue. However, there is no consensus on the perfusion and diffusion thresholds used to identify mismatch tissue in clinical and preclinical stroke research. Furthermore, in rodent stroke models differences in the evolution of ischaemic injury between strains may limit the use of a single set of threshold values. Therefore, the first aim of this thesis was to establish strain specific perfusion and diffusion thresholds to compare penumbra volume in the clinically relevant spontaneously hypertensive stroke-prone rat (SHRSP) and the normotensive control strain, Wistar-Kyoto (WKY) using 3 different methods. The SHRSP strain is characterised by the progressive development of severe hypertension which is followed by a tendency to spontaneous stroke and an increased sensitivity to experimental stroke. Experimental stroke was induced by permanent middle cerebral artery occlusion (MCAO) by the intraluminal filament method. DWI and PWI were obtained every hour from 1-4 hours post-MCAO. Strain-specific diffusion and perfusion thresholds were established from final infarct at 24 hours post-MCAO, as defined by T2 weighted imaging. The calculated ADC thresholds were comparable between the strains but the absolute perfusion threshold was significantly higher in SHRSP compared to WKY. This may be indicative of an increased sensitivity to ischaemia in the hypertensive strain. Furthermore, application of these thresholds to the acute MRI data revealed that the volume of ischaemic injury and the perfusion deficit were significantly larger in SHRSP compared to WKY and this was also reflected in the significantly larger infarct volume observed in SHRSP at 24 hours post-MCAO. Interestingly, there was evidence of a temporal increase in the volume of the perfusion deficit in SHRSP and WKY. This may indicate that there is a progressive failure of collateral blood supply in both strains following stroke. Penumbra volume was then assessed in SHRSP and WKY rats using the mismatch method and also indirectly by examining the growth of the volume of ADC derived ischaemic injury. Mismatch volume was determined by arithmetic subtraction of the volume of ischaemic injury from the volume of perfusion deficit (volumetric method) and also by manual delineation of mismatch on each of 6 coronal slices (spatial method). There was a limited volume of mismatch tissue in either strain from as early as 1 hour post-MCAO and the volumetric method generated smaller mismatch volumes than the spatial mismatch method. Mismatch volume was comparable in SHRSP and WKY from 1-4 hours post-MCAO. Penumbra was also determined retrospectively by subtracting the volume of ischaemic injury at each time point from final infarct volume. Using this method, penumbra volume was significantly larger in WKY compared to SHRSP at 30 minutes post-MCAO but penumbra volume was comparable at all later time points. This suggests that there is reduced potential for tissue salvage in SHRSP compared to WKY within the first hour following MCAO but from 1 hour onwards, there is limited potential for penumbra salvage in both strains. In addition, there was evidence of ‘negative’ mismatch tissue in SHRSP and WKY rats, where the ADC derived lesion expanded beyond the boundary of the perfusion deficit. The volume of negative mismatch tissue was comparable between the strains and was persistent over the 4 hour time course. This phenomenon may arise from the spread of toxic mediators from the ischaemic core. Oxidative stress is a major mediator of cellular injury following ischaemic stroke and reactive oxygen species, like superoxide, have multiple deleterious effects on the components of the neurovascular unit. It is well established that NADPH oxidase is the principal source of superoxide in acute ischaemic stroke and is therefore a target for potential neuroprotective strategies (Moskowitz et al, 2010). Consequently, the second aim of this thesis was to evaluate the potential neuroprotective effect of NADPH oxidase inhibition with low and high dose apocynin following permanent or transient ischaemia. Rats were administered apocynin at a dose of 5mg/kg or 30mg/kg or vehicle, at 5 minutes post-MCAO. Apocynin treatment had no significant effect on infarct volume or functional outcome at 24 hours following permanent MCAO in WKY rats. However, both low and high dose apocynin treatment significantly reduced infarct volume at 72 hours post-MCAO by 60% following 1 hour of ischaemia in Sprague-Dawley rats. Furthermore, functional outcome was improved in the low dose apocynin treated group, although this did not reach the level of statistical significance. On the basis of these results, low dose apocynin treatment was evaluated in SHRSP rats following 1 hour of ischaemia. However, apocynin treatment had no effect on the acute evolution of ischaemic injury and failed to improve stroke outcome, where the mortality rate was high in both the apocynin treated and the vehicle treated group. The conflicting effects of apocynin may be attributable to a differential expression of NADPH oxidase subunits in normotensive and hypertensive rat strains. These findings may also explain the failure of neuroprotective drugs to translate from bench to bedside, as therapies which are neuroprotective in young healthy animals may not demonstrate the same efficacy in animal models with stroke co-morbidities. Therefore, potential therapeutic strategies should be extensively evaluated in animal models with stroke risk factors before proceeding to clinical trial.

Aim: The aim of this thesis was to describe the service use, clinical outcomes and prescribing change associated with the implementation of a complex intervention designed to improve care for people with depression in a primary care setting. Background: Health systems have limited capacity to provide appropriate psychological and pharmacological treatments for people with depression. Although guidance on the treatment of depression in primary care in the UK was clarified by the National Institute for Clinical Excellence (NICE) in 2004, it is generally acknowledged that the current diagnostic classification of depression is not satisfactory. Antidepressant prescriptions have continued to rise in Scotland since the mid-1990s, even though there is no indication that the incidence or prevalence of depression is increasing. There is limited access to psychological therapies. Health services have not implemented consistent packages or systems of care in order to provide adequately for patient needs. Although the welfare of staff is critical to their therapeutic engagement with patients, this is rarely an explicit focus of health systems design. Method: This thesis describes an observational study examining the implementation of a complex intervention to improve depression care called “Doing Well”. The intervention was based in 14 General Practices in Renfrewshire, a mixed urban-rural area in Scotland. The catchment population for the study was 76,000 people. A small team of clinicians implemented a programme for people with low mood, depression and adjustment disorder, based in primary care. This programme incorporated a number of changes to standard mental health care, including the following: no “severity threshold” for referral to secondary care; the routine use of an objective measure of depression severity with continuous outcome monitoring; a paperless clinical record; prompt access to guided self-help; prompt “step-up” care to more formal psychological therapy or medical care if indicated; and careful attention to staff training and satisfaction. Findings: 1501 out of 1584 people referred to the programme met inclusion criteria and were included in the study. Three hundred and thirty-two people (22%) did not attend any appointment; 320 (21%) dropped out of treatment after at least one contact. One hundred and ninety-five people (13%) subsequently had their care transferred to other services (of which 43% were to secondary care mental health services), and 654 (44%) of patients completed treatment per protocol. There was good fidelity to the intended model of care, with patients in the “treatment complete” group receiving “brief interventions” of an average of five contacts. These contacts totalled 151 minutes over an average of 103 days of treatment. Referrals from GPs continued at a high and stable level throughout the period of the evaluation. Median waiting times of 15 days were satisfactory. The mean reduction in PHQ for patients completing treatment was 10.6 points, representing a reduction from baseline of 62%. Seventy-two percent of the treatment complete group showed a PHQ drop greater or equal than 50%, compared with seven percent in the “disengaged” and ten percent in the “transfer of care” groups. Doing Well received a lower than expected proportion of referrals from deprived areas, and there was a small negative association between clinical outcome and living in a more deprived area. Defined daily doses of antidepressants in the practices that had access to the Doing Well clinical intervention increased less rapidly (5.3% between the 12 months to June 2004 and the 12 months to June 2008) than in neighbouring areas or Scotland as a whole (15.8% over the same period). Gross ingredient costs of antidepressants in the Doing Well practices fell more substantially over this period (to 56% of baseline) than in Scotland as a whole (to 65% of baseline). Formulary compliance increased more rapidly in the Renfrewshire area than in a neighbouring area which used the same formulary, but had no contact with Doing Well. Conclusions: It was feasible to implement and sustain a system of care for depression that was consistent with NICE guidance, including the provision of some form of psychological therapy (including guided self help) for all who needed it. Access to the service was acceptable, and retention within the service compares favourably with equivalent studies in other parts of the UK. Clinical outcomes were satisfactory, but it was not possible to compare with outcomes in usual care in this observational study. Doing Well practices showed a reduction in the rate of rise of antidepressant use, although did not stop the rise altogether. The implications of this form of “stepped care” for depression for service development are discussed.

The Values History was originally developed to identify core values and beliefs important to individuals with terminal illnesses as a basis for medical treatment should they lose capacity (Doukas and McCulloch, 1991). The research shows that the standard paradigm of empowerment, which involves individuals with dementia having a clear understanding of the prognosis of the illness to make plans for the future, is complex. Twelve people diagnosed in the early stages of dementia were interviewed twice to complete individual Values Histories. Their carers were interviewed separately and then together with the participants with dementia. Despite knowing their diagnosis and appreciating the opportunity to discuss their current feelings about the illness, only a few participants were able to discuss, or indeed wanted to discuss, the prognosis or future in relation to dementia. No participants wanted to view long term care establishments. However, the research showed that the vast majority were clearly able to document their values and aspects of future care related to old age rather than dementia. Carers confirmed accuracy of their values. With regards to the impact of Values Histories on future caregivers, forty professionals were interviewed. Two Values Histories were shared with the participants and vignettes were used to explore the extent to which they would refer to individuals’ past values and wishes. The study showed that the vast majority of professionals would refer to the documents and find them useful. The majority would attempt to maintain past wishes and values, although not if it caused agitation. General values, medical values, family relationships, religious values and end of life decisions were areas that were considered most beneficial. The person’s perception of independence and future risk taking were the areas that caused most controversy.

Background: Sleep has been found to have an important restorative function. Any disturbance to sleep can be detrimental to both physical and mental health. Between 9-50% of adults with intellectual disabilities (ID) are reported to experience sleep disturbance. Support workers have a key role in identifying and responding to difficulties in the people they work with. Support workers' attributions towards the cause of these difficulties are crucial in mediating their decision to seek treatment. Their attributions may also mediate their adherence to a recommended treatment. Hence, their awareness and beliefs regarding sleep difficulties may influence their ability to recognise and seek help for sleep problems in adults they support. Method: This study utilised an exploratory vignette and questionnaire design. Questionnaires were given to 120 support workers, based in community settings, to measure their attributions to negative behaviour change and sleep problems. Support workers' attributional style was compared to their views on the acceptability of a variety of treatments for sleep disturbance. Support workers' own sleep quality was measured and compared to their attributions. Results: Support workers attributed negative behaviour change to sleep and mental health problems most strongly. Sleep problems were believed to be internal, uncontrollable and unintentional. Support workers were optimistic about treatment, particularly non-pharmacological treatments. Support workers' own sleep quality did not correlate with their attributions towards sleep problems or views on the different types of treatment. Conclusions: Support workers are optimistic that sleep problems in adults with ID can be treated, however further work is necessary to understand barriers to seeking out assessment and treatment for clients with ID.

Nuclear medicine is a functional imaging modality involving the administration of a radioactive material and the imaging of its distribution within the body. Planar nuclear medicine imaging has been used for many years in the evaluation of patients with disorders of the parathyroid and thyroid glands. Single photon emission computed tomography (SPECT) can also be carried out. This is a three-dimensional nuclear medicine imaging technique that gives both increased image contrast due to the separation of overlying structures and improved information on lesion localisation. Currently, there is no definitive procedure for parathyroid imaging, which is primarily used for localisation of adenomas or hyperplastic glands in patients with hyperparathyroidism. This information can be used to assist during surgery to remove the overactive glands. Some centres use a single-isotope, dual-phase technique with 99mTc-Sestamibi, whilst others use a dual-isotope subtraction technique with either 99mTc-pertechnetate or 123I-iodide to outline the thyroid. Single-isotope SPECT is used in some institutions but there is little information on the use of dual-isotope subtraction SPECT. Thyroid imaging with either 99mTc-pertechnetate or 123I-iodide is used to characterise thyroid disorders. The thyroid uptake can also be calculated using planar images, which can assist in clinical decision making for patients with hyper- or hypothyroidism. SPECT is not commonly used in thyroid imaging at present. This study was carried out in the Department of Nuclear Medicine, Glasgow Royal Infirmary (GRI) and was split into two distinct sections, the first being an assessment of the utility of dual-isotope subtraction SPECT for localisation of parathyroid adenomas and the second being an evaluation of the use of SPECT imaging for calculating thyroid uptake. A custom designed and built phantom was used to assess the feasibility of parathyroid and thyroid SPECT imaging and to establish suitable acquisition parameters. The results from the phantom work demonstrated that the techniques were viable and so patient SPECT data collection was commenced. A total of 32 patients with hyperparathyroidism underwent dual-isotope SPECT imaging in addition to routine planar imaging. The SPECT images were then reconstructed and a subtraction SPECT data set was produced. An observer study was then carried out with 5 experienced observers independently reviewing the images in 4 phases. In phase 1, only the dual-isotope subtraction planar images were available for review. Phase 2 was comprised of only dual-isotope subtraction SPECT images, whilst phase 3 involved review of single-isotope 99mTc-Sestamibi planar and SPECT images in the absence of 123I-iodide thyroid images. Finally, in phase 4, all of the acquired planar and SPECT images were available for review. The patients’ case notes were interrogated to obtain information on the surgical and histological reports of excised glands. A total of 17 of the 32 patients had surgery and the results were compared to the findings from the observer study to determine which type of images provided the most useful clinical information. The results of any ultrasound imaging were also obtained to compare with the surgical findings. The total number of lesions seen by the observers was higher when dual-isotope subtraction SPECT images were part of the review than when they were not, with totals in phases 1-4 of 89, 183, 89 and 155, respectively. The calculated sensitivities relative to the surgical gold standard for phases 1-4 were 49%, 77%, 45% & 64%, respectively, with ultrasound having a sensitivity of 72% for comparison. Dual-isotope subtraction SPECT therefore has a clear advantage over planar imaging for detection and localisation of parathyroid adenomas. The specificities for phases 1-4 were calculated as 61%, 31%, 29% & 27%, with the specificity for ultrasound being 33%. These specificities are, however, unreliable due to the fact that only 2 true negatives were recorded from surgery. This study showed a clear improvement in the sensitivity of dual-isotope subtraction SPECT imaging over planar imaging for the detection and localisation of parathyroid adenomas, as well as more detailed localisation information being available from the 3D images. As a result, clinical practice in the department has been changed and all patients now routinely undergo dual-isotope subtraction SPECT imaging. SPECT imaging with 99mTc-pertechnetate was carried out on 57 patients with thyroid disorders. The images were reconstructed with and without the inclusion of attenuation correction and the thyroid uptake was calculated by drawing a region of interest on each slice and summing the counts within each region. A standard acquisition was also carried out to allow accurate quantification to be performed. These uptake values were compared to those from planar imaging. Similar analysis was performed on images of a phantom to determine the accuracy of the patient uptake measurements. The various uptake values calculated from the phantom images were all similar and were slightly lower than the “true” uptake value. However, there were significant differences demonstrated between the SPECT and planar uptake values from the patient images with the SPECT uptake tending to be higher. The reasons for this are not immediately clear but are most likely related to the difference in time between injection and imaging for the planar and SPECT acquisitions at 24.5 ± 8.0 minutes (mean ± 1SD) and 71.5 ± 17.5 minutes respectively. Significant differences seen between the calculated uptake values from SPECT and planar images in the patient data sets were not evident in the phantom work, indicating that some physiological effect resulting in changing thyroid uptake over time was not taken into account. Further work could be undertaken to characterise this effect, but the method used to calculate the uptake from SPECT images is too cumbersome to be used routinely. Therefore, no change in clinical practice is anticipated for the calculation of thyroid uptake. This study has therefore resulted in a change of clinical practice for parathyroid imaging at GRI, with the introduction of dual-isotope subtraction SPECT routinely. Thyroid imaging remains unchanged, however, with the thyroid uptake being calculated from planar images.

The observation that cis interactions of neighbouring gangliosides could influence the binding capabilities of anti-glycolipid antibodies has revolutionised the glycolipid world. The realisation of the importance of these interactions has necessitated a novel platform to be developed to assay antibody to a high number of potential glycolipid antigens and their combinations (complexes). I have developed a combinatorial glycoarray technique to assay serum anti-glycolipid and anti-glycolipid complex antibodies and investigated their frequency in two populations of patients with peripheral neuropathy, Guillain Barré Syndrome and Chronic Inflammatory Demyelinating Polyneuropathy. I have compared this technique to the standardized well established technique of assaying glycolipids antibodies, namely enzyme-linked immnosorbent assay (ELISA). In addition I have employed this platform to illustrate the presence of anti-lipid antibodies within the cerebrospinal fluid (CSF) of Multiple Sclerosis (MS) patients. Furthermore though collaboration with other investigators I have demonstrated that oligoclonal immunoglobulin bands (OCB) present in the CSF of MS patients are lipid reactive. This is the first time since their original description over 50 years ago that the specificity of MS derived OCB has been described. Whilst the pathological significance of these lipid reactive antibodies remains uncertain their description provides new avenues for future research.