Thesis (M.D.) -- University of Texas Southwestern Medical Center at Dallas, 2007. / Vita. Bibliography: pp. 40-41.

This thesis embodies research investigating the role that bacterial biofilms play in the pathogenesis of chronic rhinosinusitis (CRS). It focuses on their detection on the sinus mucosa of CRS patients and the implications of their presence. Finally, it addresses deficiencies in the innate immune system that may predispose to their development in this condition. Bacterial biofilms are structural assemblages of microbial cells that encase themselves in a protective self-produced matrix and irreversibly attach to a surface. Their extreme resistance to both the immune system as well as medical therapies has implicated them as playing a potential role in the pathogenesis of many chronic diseases. Although their role in many diseases is now well established, their objective presence and importance in CRS remains largely unknown. Chapter 1 of this thesis reviews the current literature pertaining to CRS and biofilms and critically evaluates the small body of research relating to this topic. Chapter 2 describes the development of a sheep model to study the role of bacterial biofilms in rhinosinusitis. It compares the use of traditional electron microscopy (EM) and more recent confocal scanning laser microscopy (CSLM) in the detection of biofilms on the surface of sinus mucosa. The results of this study inferred a causal relationship between biofilms and the macroscopic changes that accompany rhinosinusitis. Furthermore it illustrated the superiority that CSLM has over EM in the imaging of biofilms on sinus mucosa Chapter 3 and 4 outline the results of human studies utilizing the more objective CSLM to evaluate the prevalence of bacterial biofilms on the sinus mucosa of CRS patients and their effect on post-operative mucosal healing. The results of these studies demonstrated a biofilm prevalence of approximately 50% in the CRS population studied and suggested, that biofilm presence may predispose to adverse post-operative outcomes following sinus surgery. Chapter 5 and 6 describe experiments examining the level of the innate immune system’s anti-biofilm peptide lactoferrin, in patients with CRS. Lactoferrin was found to be downregulated at both an mRNA and protein level in the majority of CRS patients, with biofilm positive patients demonstrating the most significant reduction. In summary, this thesis provides further evidence that bacterial biofilms play a major role in the pathogenesis and disease persistence in a subset of CRS patients. Deficiencies in components of the innate immune system, such as lactoferrin, may play an important role in the predisposition of certain individuals to the initial development of bacterial biofilms. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1346621 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine 2008

This study was a cross-sectional epidemiologic evaluation of the clinical, sociodemographic, lifestyle and hospital utilisation characteristics of patients with diabetes, chronic obstructive pulmonary disease and chronic heart failure. Patients were enrolled in chronic disease management services of the Northern Alliance Hospital Admission Risk Program-Chronic Disease Management (Northern Alliance HARP-CDM Program). The program was established in accordance with the Department of Human Services’ (Victoria, Australia) initiative to intervene against increasing acute hospital demand by patients with chronic disease and complex needs. Amongst others, the Northern Alliance HARP-CDM Program provides services for patients with diabetes, chronic heart failure and chronic obstructive pulmonary disease. Patient cohorts with these three chronic diseases were the focus of this study. The Northern Alliance HARP-CDM Program catchment comprises of a culturally and linguistically diverse (CALD) population in the northern part of metropolitan Melbourne. Patients in this region mainly access acute hospital services at the Northern Hospital. The study sought to explore whether the CDM services enrolled patients whom based on their characteristics, fit the risk profile of the intended HARP-CDM target patient population. / The study cohorts demonstrated a CALD make up of above Victorian state averages. The majority (60%) were born overseas, preferred a language other English and were over 60 years old. In contrast to previously published studies, CALD did not demonstrate a significant contribution to disease control, quality of life or level of hospital utilisation. Place of residence for these patients showed clusters within some Local Government Areas. This has implications for service location, access and disease surveillance. Also, it presents opportunities for area targeted health promotion and prevention and overall service location. The majority (77%) of those with chronic heart failure had an abnormal left ventricular ejection fraction. The diabetes cohort was characterised by higher HbA1c (9%) than the target of less than 8%. Similarly the patients had greater than recommended waist circumferences (Males 106cm vs. 94cm; Females 106 vs. 80cm) places them at an increased risk of cardiovascular disease. For those with COPD, 42% had severe pulmonary impairment (FEV%predicted ≤ 40%) while 36% were moderate in the moderate category. / There was increased hospital utilisation with increasing age for those with COPD. With the exception of the diabetes cohort, there was no significant evidence as to the role of ethno-cultural factors in the study cohorts’ health, quality of life or level of hospital utilisation. However, ethno-cultural factors may contribute to the complexity of patient management processes and warrants further investigation. / Prior to enrolment in the Northern Alliance HARP-CDM Program, patients who could be considered high users of emergency department services made up 20% of those in the diabetes service, 43% in the COPD service and 50% amongst those in the CHF service. Similar figures for hospital admissions ranged from 20% for the diabetes services to 56% for the CHF service cohorts respectively. Although the diabetes service was the biggest of the three the majority of patients in the service had no previous history of acute hospital utilisation. Members of the diabetes service cohort were characterised by hospital utilisation rates lower than the Northern Hospital’s (ED: 34 vs. 72 per 100 patients, Admissions: 33 vs. 68 per 100 patients in the Pre HARP-CDM Period). Patients in the COPD service (ED: 115 Pre and 158 during HARP-CDM) and CHF service (160 Pre and 159 during HARP-CDM) had ED presentation rates per 100patients that were higher than the hospital’s (72 and 69). / The rates suggest the first 14 months of the Northern Alliance HARP-CDM Program were associated with increased hospital utilisation by patients enrolled the Northern Alliance HARP-CDM Program. The increments were greater than increases for the Northern Hospital for the same periods. Contrary to the intended goal of reducing acute hospital utilisation, the majority of the clientele did not fit the primary HARP-CDM Program criteria of high acute hospital users. But patients who were enrolled following previous hospital utilisation were well-targeted. However there are several patients who are likely HARP-CDM Program candidates who fall though the gaps between the acute hospital services and the program. / It is recommended the program and services increase enrolments and access for the target patient populations. There is a need for early intervention chronic disease management and health promotion. This service would cater for clients who by virtue of having a chronic disease are at risk but are currently not high acute hospital users. Such a service would free up vacancies in the Northern Alliance HARP-CDM Program, thus enabling increased intake and equitable access for the target patient population, especially those who fall though the gaps as referred to earlier. Funding for such a service is available through DHS. In light of strong evidence for exercise rehabilitation and its ability to positively impact patient outcomes, quality of life, survival and hospital utilisation, consideration needs to be given to this as part of the Northern Alliance HARP-CDM Program chronic disease management care model.

<p>The aim of this study was to compare perceived disability in daily activities, anxiety and depression for patients with chronic pain (>3 month), before and after rehabilitation. Another aim was to examine if there were any correlations between disability in daily activities and the extent of anxiety and depression before and after rehabilitation.</p><p>For the measurements, Disability Rating Index (DRI) that measures disability in daily activities, and Hospital Anxiety and Depression Scale (HADS) ) which measures the extent of anxiety and depression were used. The study was carried out with 50 patients who had suffered from chronic pain and with the objective to return to work after rehabilitation. Of these, 90 % were female. The measurements were carried out at three measure points; before rehabilitation, seven weeks after rehabilitation and one year after rehabilitation.</p><p>The main result did not show any statistically significant improvement in ability to perform daily activities.</p><p>The only significant difference that emerged was an improvement in anxiety seven weeks after rehabilitation compared with before. There were significant correlations between the ability to perform daily activities and anxiety and depression before rehabilitation. There was also a significant correlation between the ability to perform daily activities and depression after rehabilitation.</p><p>Conclusions drawn from this paper are that there seems to be a decrease in feelings of anxiety after rehabilitation and also that there appears to exist a correlation between disability and depression.</p>

The aim of this study was to compare perceived disability in daily activities, anxiety and depression for patients with chronic pain (&gt;3 month), before and after rehabilitation. Another aim was to examine if there were any correlations between disability in daily activities and the extent of anxiety and depression before and after rehabilitation. For the measurements, Disability Rating Index (DRI) that measures disability in daily activities, and Hospital Anxiety and Depression Scale (HADS) ) which measures the extent of anxiety and depression were used. The study was carried out with 50 patients who had suffered from chronic pain and with the objective to return to work after rehabilitation. Of these, 90 % were female. The measurements were carried out at three measure points; before rehabilitation, seven weeks after rehabilitation and one year after rehabilitation. The main result did not show any statistically significant improvement in ability to perform daily activities. The only significant difference that emerged was an improvement in anxiety seven weeks after rehabilitation compared with before. There were significant correlations between the ability to perform daily activities and anxiety and depression before rehabilitation. There was also a significant correlation between the ability to perform daily activities and depression after rehabilitation. Conclusions drawn from this paper are that there seems to be a decrease in feelings of anxiety after rehabilitation and also that there appears to exist a correlation between disability and depression.

Chronic exertional compartment syndrome (CECS) of the lower leg, defined as a condition with exercise-induced pain due to increased intramuscular pressure (IMP), has previously mainly been described in running athletes, and etiologic factors are poorly described. CECS has not been reported to occur together with other diseases and information about consequences on muscles morphology after treatment with fasciotomy is largely unknown. We investigated etiologic and pathophysiologic aspects to CECS in a consecutive series of 63 patients with exercise-related leg pain and in 17 diabetic patients with symptoms of intermittent claudication but no circulatory insufficiency. Clinical examination, radiography, scintigraphy and IMP measurements at rest and after reproduction of symptoms were done. Patients with CECS were recommended treatment with fasciotomy. Biopsies were taken from the tibialis anterior muscle at time of fasciotomy and at follow-up 1 year later. For comparison muscle samples were taken from normal controls. Enzyme- and immunohistochemical and morphometric methods were used for analysis of muscle fiber morphology/pathology, fiber phenotype composition, mitochondrial oxidative capacity and capillary supply. Thirty-six of the 63 patients fulfilled the criteria for diagnosis of CECS in the anterior tibial compartment. The CECS patients could be divided into different etiologic groups: 18 healthy, 10 with history of trauma against the lower leg, 4 diabetic patients and 4 others. Only 5 of 36 CECS patients were athletes. The results after fasciotomy were good or excellent in 41 of 57 treated legs.  Sixteen of the 17 diabetic patients were diagnosed with CECS, 11 with diabetes type 1 and 5 with type 2. The diabetic patients differed from the other groups with longer symptom-duration, shorter pain-free walking distance, firm and tender lower leg muscles and higher IMP. The postoperative outcome was good or excellent in 15 of 18 treated legs. The muscle biopsies taken at fasciotomy showed frequent histopathological changes including small and large sized fibers, fiber atrophy, internal myonuclei, split fibers, fibrosis, disorganization of mitochondria in contrast to healthy CECS subjects having low muscle capillarization as the main finding. Muscular abnormalities were generally more complex, severe and widespread in diabetic patients. After 1 year, the majority of CECS patients could return to unrestricted physical activity and the histopathological muscle changes were clearly reduced. The muscle fiber size was larger and the muscles contained signs of regeneration and repair. Remaining muscle abnormalities were present mainly in diabetic patients. CECS is a new differential-diagnosis in diabetic patients with symptoms of claudication without signs of vascular disease. A low ability for physical activity, reflected by the signs of both myopathy and neuropathy, indicates that high IMP and circulatory impairment has deleterious effects for the involved muscles. Increased physical activity and normalization of muscle morphology 1 year after treatment shows the benefit of fasciotomy. The more severe clinical and morphological findings in diabetic compared to healthy subjects with CECS indicate differences in the pathogenesis. The unrestricted physical ability after treatment is very important for diabetic patients, since physical activity is an essential part of the therapy of the disease.

Chronic pain conditions can be extremely challenging to deal with in the workplace. The implications of these conditions extend far beyond the employees themselves and can create significant organizational impacts. The Chronic Pain Self-Management Program was developed by Dr. Sandra LeFort, and was originally based on the generic Stanford model of self-management. The six-week program, delivered weekly, is designed to explore and instruct those with chronic pain on different aspects of their condition. This pilot study used a mixed method design to evaluate the effectiveness of Chronic Pain Self-Management Program in the workplace. The quantitative measures for this study were unable to demonstrate the effectiveness of the workshop due to a lack of statistical significance. Through the qualitative measures it was possible to delve into how the chronic pain condition manifests itself in the workplace and what support systems are available for those with chronic pain. There are definitely some positive implications from this pilot research, but through further research it is possible to truly understand how people live with chronic pain in the workplace and how their conditions can be made more manageable. / UOIT

Fibromyalgia Syndrome (FMS) and Chronic Fatigue Immune Dysfunction Syndrome (CFIDS) are primarily womens syndromes. Both syndromes are highly contested within the biomedical and scientific communities and within the general population. Because there is no apparent cause for the syndromes and no available treatment, women living with FMS and/or CFIDS must live with difficult and disabling symptoms. <p>This research also analyzes the metaphors used in the scientific and biomedical literature to describe the same symptoms as listed above. A comparison is drawn between this analysis and that focused on the womens use of metaphors. It is found that although many of the metaphors are the same, they differ in discursive employment. Environmental metaphors, along with metaphors of fracture, harm and productivity are used by the research participants with a very different intent than how the same metaphors are used in the biomedical literature. The women used the metaphors to reveal the ways in which their symptoms are influenced by the social and cultural forces in their everyday lives. The biomedical and scientific use of metaphors reinforced the highly contested view that the symptoms are influenced more by individual psychological and emotional deficiencies than by broader structural forces.

B-cell chronic lymphocytic leukemia is the most common leukemia in the adult population of Western developed countries. In 2005, an estimated 9,730 adults in the United States will be diagnosed with B-CLL and an estimated 4,600 deaths will occur. B-CLL is a common heterogeneous malignant disease with variable outcome. B-CLL is divided into two groups based on whether somatic hypermutation is observed in the variable region of the immunoglobulin heavy-chain locus (IgVH). The two distinct groups are named mutated and unmutated. The B-CLL mutated group has a more favorable prognosis than the unmutated group. Gene expression profiling has been used successfully to decipher the biological and clinical diversity of many leukemias and lymphomas. Recently, other small RNAs (microRNAs) have been shown to be important in hematopoiesis. MicroRNAs are small 20-28 nucleotide RNAs that are believed to control many important cellular and developmental processes by posttranscriptional gene silencing, translational repression, and modulating epigenetic events. We are interested in whether microRNA expression correlates with the mutational status of IgVH. This study is significant in the following ways: (1) microRNAs may become surrogate markers for the mutational status of IgVH of B-CLL, which implies a more rapid diagnostic means as compared to the current practice, and (2) microRNAs, in the particular context of B-CLL, may play some significant roles in a gene regulatory network that is further responsible for chromosomal abnormalities found in B-CLL. This thesis presents a study comparing microRNA expression in mutated and unmutated B-CLL groups. Instead of using a genome-wide expression profiling strategy, we selected a specific set of microRNAs based on their chromosome locations and mRNA targets. Specifically, we chose the following eight microRNAs (with their chromosomal abnormalities): mir16-1 (deletion 13), let-7i (trisomy 12), mir196-2 (trisomy 12), mir26a-2 (trisomy 12), mir-34b (deletion 11), mir-125b (deletion 11), mir-181C (trisomy 19), mir-125a (trisomy 19). We used solution hybridization assays to monitor the expression of microRNAs. We successfully characterized the microRNA expression in twelve B-CLL patient samples (eight mutated and four unmutated). Among the eight microRNAs examined, three (mir196-2, mir-125a, mir-125b) are not expressed in the two B-CLL groups, four (mir16-1, mir26a-2, let-7i, mir-34b) have significant differences in expressions over the two groups, and one (mir-181c) has no significant difference in expressions over the two groups.

Chronic pain in the aged is a widespread phenomenon, and morphine is the most commonly used narcotic analgesic for treatment. Despite that fact, there are relatively few published studies examining the impact of advanced age on morphine analgesia. We hypothesized that aged rats would be less sensitive to morphine than adults, and that aged animals would have reduced mu-opioid receptor (MOR) binding and expression in the ventrolateral periaqueductal gray, a brain region responsible for morphine analgesia. Using a model of persistent inflammatory pain, we found that morphine was significantly less effective in aged males compared to adult males, and that aged males and females experience a reduction in MOR binding and expression compared to adults. These results suggest that there are clear age differences in morphine efficacy, and that reductions in MOR binding and expression in the periaqueductal gray could underlie those differences.