Malnutrition is present in up to 48% of chronic kidney disease patients on the initiation of renal replacement therapy (dialysis)1. At this time, malnutrition is an independent and significant predictor of morbidity and mortality2. As a consequence of progressive deterioration in kidney function, symptoms of decreased appetite and reduced intake are common factors leading to the decline in nutritional status3. However, at present there is little evidence to inform nutrition assessment and intervention for pre-dialysis chronic kidney disease (CKD). The purpose of this study was to provide evidence for the nutritional management of CKD patients prior to dialysis with an aim to optimise nutritional status. To address this, an investigation comprising of two phases examining nutrition assessment and intervention in a sample of pre-dialysis Stage IV and V CKD patients was undertaken. Both phases of the study were conducted through Royal Brisbane and Women’s Hospital (RBWH) Department of Renal Medicine pre-dialysis clinic. Participants met the following criteria: adult (&gt18 years) Glomerular Filtration Rate (GFR) &lt30ml/min CKD, not previously seen by a dietitian for Stage IV CKD, absence of communication or intellectual impairment inhibiting their ability to undertake the intervention and an absence of malnutrition from a cause other than CKD. Phase I was a cross-sectional investigation into the performance of a range of tools assessing nutrition status, conducted at baseline of Phase II. Phase II was a randomisedcontrolled trial designed to determine if providing individual nutrition counselling with regular telephone follow-up resulted in improved body composition, nutritional status, dietary intake and quality of life, compared with standard care. A range of intermediate, clinical and patient-centred outcome measures were collected at baseline and twelve weeks. Body composition was measured by total body potassium counting (TBK), considered a gold-standard measure of body cell mass (BCM, the body’s functional metabolising tissue). Nutritional status was measured using Subjective Global Assessment (SGA) and a number of modified versions of SGA, 7-point SGA, Malnutrition Inflammation Score (MIS) and the scored Patient-Generated Subjective Global Assessment (PG-SGA). Dietary intake was measured using 3-day food records. Quality of life was measured by Kidney Disease Quality of Life Short Form version 1.3 (KDQOL-SFTM v1.3 © RAND University), combining the Short Form-36 (SF-36), with a kidney disease-specific module4. Statistical analysis was carried out using SPSS Version 13 (SPSS Inc, Chicago, IL, USA). Phase I analysis was based on descriptive and bi-variate statistics, including chi-square, t-test and ANOVA. For phase II, change variables (Week 12 – Week 0) were created for the outcome measures (BCM, SGA tools, dietary intake (energy and protein) and the 18 KDQOL-SFTM subscales). The assessment of change in outcome measures by treatment group was undertaken by ANCOVA, adjusting for baseline values. Further multivariate analysis (ANCOVA and MANCOVA models) were created for outcome variables when confounding variables were identified and adjusted for. In Phase I, 56 patients (Male n=34; age mean (±SD) 70.7 (±14.0); GFRMDRD 22.4 (±6.5) mL/min) underwent baseline assessment. In this population the prevalence of malnutrition was 19.6% (n=11, SGA B; no C ratings). Malnutrition was associated with lower body cell mass (mean BCM, 26.3 vs. 33.4 kg p=0.007), body weight (64.8 vs. 76.1 kg p=0.042), BMI (23.7 vs. 27.6 kg/m2 p=0.015) and greater weight loss over previous 6 months (-6.2 vs. -0.1 kg p=0.004). Body cell mass indexed for height (BCM-I kg/m3.5) had a relationship with MIS (r=-0.27 p=0.063) and scored PG-SGA (r=-0.27 p=0.060), but not with 7-point SGA (F(4) 2.24 p=0.080). PG-SGA best discriminated malnutrition based on a BCM-I cut-off of &lt5.25kg/ m3.5 of all the modified SGA tools. The scored PG-SGA including the global SGA rating is recommended for use in pre-dialysis CKD. In Phase II, 50 patients, (Male n=31 (62.0%); age 69.7 (±12.0) years; GFRMDRD 22.1 (±6.9) ml/min) completed the 12 week study period (intervention n=24; standard care n=26). At 12 weeks, there was a clinically significant improvement in all outcome measures in the intervention group. There was a 3.9% (95% CI, -1.0 to 8.7%) mean difference in change for Body Cell Mass between the treatment groups, represented by a significant decrease in the standard care group and maintenance in the intervention group. Nutritional status measured by SGA improved or was maintained (24/24) in the intervention group, however, decreased in 14% (4/26) of the standard care group. Energy intake significantly improved in the intervention group resulting in a mean difference in change of 17.7kJ/kg (8.2 to 27.2 kJ/kg). Quality of life improved significantly in 10 of the 18 sub-scales in the intervention group. Significant effect modification for gender was apparent for many of the outcome variables, with females responding most significantly to the intervention treatment. This study concluded that, overall, structured nutrition intervention limits the deterioration in nutritional status, improves dietary intake and quality of life in patients with CKD prior to the onset of renal replacement therapy. This thesis makes a significant contribution to the evidence base for nutritional management of pre-dialysis Stage IV CKD. The use of SGA for nutrition assessment and including PG-SGA to measure change is recommended for routine nutrition assessment of pre-dialysis CKD. The provision of individual nutrition counselling with regular follow-up, with a focus on promoting intake provides beneficial patient outcomes supporting optimal nutritional status in pre-dialysis CKD patients.

Master of Philosophy (MPhil) / Background: Physical deconditioning is often associated with chronic pain and is believed to be a result of gradual movement inhibition and reduction of physical activities. It is common for chronic pain sufferers to present with limited muscle extensibility and poor tolerance to physical movement. Exercises are therefore prescribed to assist in regaining muscle extensibility, strength, fitness and endurance. Of particular interest is stretch, a type of exercise aimed at increasing muscle extensibility. Stretch is commonly prescribed as part of physical rehabilitation in pain management programs, yet little is known of its effectiveness in the chronic pain population. Aim: The aim of this randomised controlled trial was to investigate the effects of a three-week stretch program on muscle extensibility and stretch tolerance in patients with chronic musculoskeletal pain. Methods: Thirty adults with pain persisting for at least three months and limited hamstring muscle extensibility were recruited from patients enrolled in a multidisciplinary pain management program at a Sydney Hospital. A within-subject design was used, with one leg of each participant randomly allocated to an experimental (stretch) condition and the other to a control (no stretch) condition. The hamstring muscles of the experimental leg were stretched for one minute a day over a three-week period, whilst the hamstring muscles of the control leg were not stretched during this time. This intervention was embedded within a pain management program and supervised by physiotherapists. Primary outcome measures were muscle extensibility and stretch tolerance, reflected by passive hip flexion angles produced with standardised and non-standardised torques, respectively. Initial measures were taken prior to the first stretch on day one and final measures were taken one to two days after the last stretch. A blinded assessor was used for all testing. Results: After three weeks of intervention, stretch did not increase muscle extensibility (mean between-group difference in hip flexion was 1 degree; 95% CI -2 to 4 degrees) but did improve stretch tolerance (mean between-group difference in hip flexion was 8 degrees; 95% CI 5 to 10 degrees). Conclusion: Three weeks of stretch increases tolerance to the discomfort associated with stretch but does not change muscle extensibility in patients with chronic musculoskeletal pain. This study provides support for the ongoing incorporation of stretch in pain management programs, where stretch may be conceptualised as a graded exposure to movement and assisting in the restoration of normal activity and function.

B cell chronic lymphocytic leukemia (B-CLL) is a hematologic neoplasm characterised by the proliferation and accumulation of sIgM+/D+ B cells that fail to progress to the final stages of B cell development. The malignant cells in B-CLL also express the pan-T cell antigen CD5, suggesting that CLL is a malignancy of the CD5+ subset of B cells. Additional characteristics of the malignant clone include a low proliferative index, enhanced in vivo survival and constitutive expression of the anti-apoptosis oncoprotein bcl-2. The behaviour of leukemic CD5 B cells in vitro contrasts their arrested in vivo state. That is, despite the majority of cells being arrested in the G0 phase of the cell cycle, the leukemic B cells are not irreversibly frozen as they can be induced to differentiate to Ig-secreting cells under appropriate in vitro conditions. Furthermore, leukemic CD5 B cells rapidly undergo death by apoptosis following in vitro culture. This thesis describes the requirements for in vitro activation of leukemic CD5+ B cells, the characterisation of the events involved in apoptosis of these cells as well as the identification of various growth factors capable of modulating these events. Stimulation of unfractionated peripheral blood lymphocytes (PBLs) from three patients with B-CLL with the phorbol ester PMA and the mitogens PHA and PWM resulted in significant increases in cell proliferation, RNA synthesis and 1gM secretion when compared to unstimulated cell populations. PMA was the most potent inducer of 1gM secretion and this occurred irrespective of the presence of residual T cells. PMA-induced proliferation and RNA synthesis were also independent of T cells. However, in the presence of T cells, these parameters of cellular activation were enhanced during in vitro culture. Thus, the inductive ability of PMA on leukemic CD5 B cells was independent of T cells. In contrast, activation and differentiation of the leukemic CD5 B cells into 1gM-secreting cells following culture with mitogens did not occur in the absence of T cells. Interestingly, co-stimulation of leukemic CD5+ B cells with PMA and anti-Ig induced cellular responses that exceeded those induced by either activator alone. Thus, leukemic CD5+ B cells from patients with B-CLL can be activated in vitro and differentiate in response to stimulation via both T cell-dependent and T cell-independent mechanisms. Apoptotic cell death was characterised in purified leukemic CD5 B cells obtained from six B-CLL patients. All leukemic CD5 B cell populations entered an apoptotic pathway in vitro as evidenced by a reduction in cell size, loss of cell viability and fragmentation of DNA into multimers of -180 base pairs. Following 24 hours of in vitro culture 24.0±16% of DNA was fragmented. After 8 days, the majority of DNA was fragmented, and fewer than 10% of cultured cells were viable. Examination of bcl-2 expression in the malignant B cells by flow cytometry revealed a unimodal pattern of expression in greater than 85% of cells from each B-CLL patient prior to culture. During in vitro culture, bcl-2 expression became bimodal such that the B cells displayed a bcl-2hjgh and bcl-2iow phenotype. The level of expression by the bCl2hjgh cells was similar to that observed prior to in vitro culture, indicating that bcl-2 is down-regulated in apoptosing cells. Interestingly, despite this downregulation, the overall number of cells positive for bcl-2 remained constant. This suggests that the enhanced survival of leukemic CD5+ B cells in vivo is mediated by the sustained expression of bcl-2 and that additional mechanisms exist capable of overriding the protective effect of bcl-2 when bcl-2 is present at reduced levels. Leukemic B cell apoptosis has previously been reported to be delayed or prevented by IL-4, IFN-y and IFN-a. These results were confirmed in this study where it was found that culture of leukemic CD5 B cells with IL-4 or IFN-y enhanced cell viability and delayed apoptosis in 6/6 and 5/6 populations of leukemic B cells, respectively. This function was also found to be shared by IL-2, IL-6, IL-13 and TNF-a as these cytokines enhanced cell viability and delayed apoptosis in some of the cell populations examined at a level similar to that observed for IL-4 and IFN-y. These cytokines may mediate their effect via the expression of bcl2 as culture in the presence of IL-2, IL-4, IL-6, IL-13, IFN-y or TNF-a resulted in a higher percentage of cells displaying the bcl-2high phenotype, compared to unstimulated cells. Taken together, these results suggest that autocrine and/or paracrine growth loops may play a role in the pathogenesis of B-CLL and that cytokines that prevent apoptosis in vitro may be targets for treatment of this B cell malignancy.

The grief experienced by mothers and fathers when their child is diagnosed with a life threatening chronic-illness was investigated in order to validate the presence of grief in these parents and look at the factors that influence it. More specifically, I was interested in whether the grief experience differed for mothers and fathers and the impact that perceptions and coping have on both these gender differences in grief and on grief in general. The particular population investigated in this study were parents of children with Cystic Fibrosis. Participants were recruited through questionnaires randomly sent out by the National Cystic Fibrosis Association. In all, 37 mothers and 15 fathers took part. Results not only confirmed presence of grief in these parents but also indicated that this grief differs for mothers and fathers, with mothers reporting significantly higher levels of physical distress. In line with the literature no gender differences were found in regards to perception of impact parents felt their child's chronic-illness had had on their lives. Contrary to what was expected, however, no differences were found amongst the coping strategies used by mothers and fathers. In regards to the question of which factors have the greatest impact on the grief experienced by mothers and fathers combined, the coping strategy of self-blame was found to be the most important, followed closely by negative perceptions. The significance of these findings and their implications for parents and the people who work with them was discussed.

Masters of Science in Medicine / The relationship between COPD and laryngopharyngeal sensitivity has not been previously determined. Limited research into the relationship between COPD and swallow function suggests that patients with COPD are at increased risk of aspiration. One possible mechanism for this is a reduction in laryngopharyngeal sensitivity (LPS). Reduced laryngopharyngeal sensitivity (LPS) has been associated with an increased risk of aspiration in pathologies such as stroke, however impaired LPS has not been examined with respect to aspiration risk in COPD. The Aims of this study were to investigate the effect of COPD on laryngopharyngeal sensation using Laryngopharyngeal Sensory Discrimination Testing (LPSDT) and to determine whether a relationship between LPS and swallow function in patients with proven COPD exists. Method: 20 patients with proven COPD and 11 control subjects underwent LPSDT utilising an air-pulse stimulator (Pentax AP4000) via a nasendoscope (Pentax FNL10AP). The threshold of laryngopharyngeal sensation was measured by the air pressure required to elicit the laryngeal adductor reflex (LAR). A number of further examinations were also completed for COPD subjects. These included respiratory function testing, self-reporting questionnaire on swallowing ability (SSQ), bedside clinical examination of swallowing (MASA) and endoscopic assessment of swallowing (EAS). Results: subjects with COPD had a significantly higher LAR threshold when compared to their normal healthy counterparts (p<0.001). Positive correlations were identified for the relationships between MASA score and EAS results for presence of laryngeal penetration / aspiration (p<0.04), vallecular residue (p<0.01) and piriform residue (p<0.01). Conclusion: Patients with COPD have significantly reduced mechanosensitivity in the laryngopharynx. Patients with COPD also have impaired swallow function characterised primarily by pharyngeal stasis. These changes may place patients with COPD at increased risk of aspiration.

Master of Philosophy (MPhil) / Background: Physical deconditioning is often associated with chronic pain and is believed to be a result of gradual movement inhibition and reduction of physical activities. It is common for chronic pain sufferers to present with limited muscle extensibility and poor tolerance to physical movement. Exercises are therefore prescribed to assist in regaining muscle extensibility, strength, fitness and endurance. Of particular interest is stretch, a type of exercise aimed at increasing muscle extensibility. Stretch is commonly prescribed as part of physical rehabilitation in pain management programs, yet little is known of its effectiveness in the chronic pain population. Aim: The aim of this randomised controlled trial was to investigate the effects of a three-week stretch program on muscle extensibility and stretch tolerance in patients with chronic musculoskeletal pain. Methods: Thirty adults with pain persisting for at least three months and limited hamstring muscle extensibility were recruited from patients enrolled in a multidisciplinary pain management program at a Sydney Hospital. A within-subject design was used, with one leg of each participant randomly allocated to an experimental (stretch) condition and the other to a control (no stretch) condition. The hamstring muscles of the experimental leg were stretched for one minute a day over a three-week period, whilst the hamstring muscles of the control leg were not stretched during this time. This intervention was embedded within a pain management program and supervised by physiotherapists. Primary outcome measures were muscle extensibility and stretch tolerance, reflected by passive hip flexion angles produced with standardised and non-standardised torques, respectively. Initial measures were taken prior to the first stretch on day one and final measures were taken one to two days after the last stretch. A blinded assessor was used for all testing. Results: After three weeks of intervention, stretch did not increase muscle extensibility (mean between-group difference in hip flexion was 1 degree; 95% CI -2 to 4 degrees) but did improve stretch tolerance (mean between-group difference in hip flexion was 8 degrees; 95% CI 5 to 10 degrees). Conclusion: Three weeks of stretch increases tolerance to the discomfort associated with stretch but does not change muscle extensibility in patients with chronic musculoskeletal pain. This study provides support for the ongoing incorporation of stretch in pain management programs, where stretch may be conceptualised as a graded exposure to movement and assisting in the restoration of normal activity and function.

Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.

Thesis (Ph. D.)--University of Nevada, Reno, 2006. / "December 2006." Includes bibliographical references (leaves 61-72). Online version available on the World Wide Web. Library also has microfilm. Ann Arbor, Mich. : ProQuest Information and Learning Company, [2006]. 1 microfilm reel ; 35 mm.

Thesis (Ph. D.)--Virginia Commonwealth University, 2006. / Prepared for: School of Nursing. Bibliography: leaves 117-143. Also available online via the Internet.

Thesis(M.S.)--Auburn University, 2005. / Abstract. Vita. Includes bibliographic references.