No description available.

Bone remodelling, the process by which the skeleton adapts to environmental changes, is dependent on the actions of osteoclasts that resorb bone and osteoblasts which make new bone matrix. Aberrant remodelling underpins bone loss in several debilitating skeletal diseases such as osteoporosis, metastatic breast cancer and multiple myeloma. Changes in remodelling activity can also arise as a consequence of therapeutic intervention for instance intravenous bisphosphonate treatment is associated with osteochemonecrosis of the jaw and localised osteoradionecrosis is a common side effect of radiotherapy. Hyperbaric oxygen is often used as an adjunctive therapy in the treatment of these disorders. HBO involves the administration of 100% oxygen at atmospheric pressures greater than one in sealed chambers. The following studies aimed to evaluate the effect of HBO, hyperoxia, and pressure on RANKL-induced osteoclast differentiation and bone resorption from RAW264.7 and human peripheral blood mononuclear cells (PBMC), and osteoblast differentiation in vitro. The study also aimed to further examine the effect of HBO on ex vivo osteoclast formation from peripheral blood monocytes obtained from patients undergoing HBO. Daily exposure to HBO for ninety minutes significantly suppressed osteoclast differentiation and bone resorption in mouse and human monocytes in normoxic and hypoxic conditions in vitro. The suppressive action of HBO on osteoclast formation was associated with a significant reduction in HIF-1α and RANK mRNA expression and HBO also caused a significant reduction in NFATc1 and DC-STAMP expression. This study has for the first time shown that HBO is able to reduce the ability of precursors to form bone resorbing osteoclast. HBO also suppressed the ability of peripheral blood monocytes to develop into RANKL-induced resorptive osteoclasts. In an ex vivo culture system the suppressive effect of HBO was meditated by an action prior to activation of osteoclast differentiation by RANKL and must therefore be an inhibitory effect on the ability of precursors to differentiate along the osteoclastic lineage. HBO also accelerates the rate of osteoblast differentiation and augments early stages of mineralization and has a more pronounced effect than hyperoxia or pressure alone. HBO enhanced bone nodule formation and ALP activity in human osteoblasts. Furthermore HBO promoted the expression of type I collagen and Runx-2 in both normoxic and hypoxic conditions. HBO had a greater effect on these key markers of osteoblast differentiation than hyperoxia or pressure alone. This study suggests that HBO suppresses osteoclast activity and promotes osteoblastic bone formation, which may at least in part mediate its beneficial effects on necrotic bone. This provides evidence supporting the use of HBO as an adjunctive therapy to prevent osteoclast formation in a range of skeletal disorders associated with low oxygen partial pressure. The study also provides further support for the use of HBO in the treatment of skeletal disorders associated with excessive resorption such as osteomyelitis, and also provides a potential mechanism through which short term HBO may help fracture healing.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2004. / Härtill 6 uppsatser.

Thesis (M.Med.Sc.) - University of Queensland, 2003. / Includes bibliography.

Spinal cord injury (SCI) is a physically and mentally devastating condition for which there is no curative treatment. It involves primary trauma from the impact and secondary damage in the form of biochemical cascades that threaten the integrity of functional tissue. Therapeutic interventions can only prevent secondary damages, given the irreversibility of the primary laceration. Experimental therapies for SCI can aim to promote neuronal growth and/or regeneration, promote neuroplasticity in surviving neurons and networks, and enhance neuroprotection, or the survival of spared neurons. Surgical decompression and hypothermia are neuroprotective strategies that usually precede rehabilitational strategies in SCI. Hyperbaric oxygen (HBO) treatment constitutes another promising therapy that can increase the amount of oxygen dissolved in the blood, and therefore, the amount delivered to tissues. Both pre-clinical and clinical studies have illustrated that HBO therapy can enhance motor recovery and exert neurological improvements after SCI. A plethora of pre-clinical studies have elucidated several aspects of its function in SCI; HBO seems to suppress apoptosis, edema, and inflammation, as well as mitigate oxidizing conditions. It can also promote angiogenesis, enhance nerve conduction, and inhibit neural degeneration. The limited number of clinical studies and the heterogeneity of protocols allow for fewer conclusions on the roles of HBO in human SCI: motor benefits are hinted in several clinical trials, while neuroprotective effects include increases in blood oxygen, and suppression of inflammatory responses. However, the number and variety of pre-clinical studies suggest that HBO can exert additional neuroprotective benefits in human SCI, which remain to be explored in the future.

The quality of healthcare in low-resource countries is often limited by the environment, lack of funds, staff availability, electricity availability, and more. In the words of a Malawian physician, medicine can feel like improvisation, wherein one must make due with available resources rather than desired resources. One prevalent problem among low-resource hospitals is the functionality and longevity of medical equipment. A large percentage of all medical equipment in Malawian hospitals is donated, resulting in a wide spectrum of models, necessary spare parts, and functionality. These machines can break quickly due to heavy use prior to donation, missing user and maintenance manuals, and a lack of replacement parts. Thus, finding necessary life-saving equipment in Malawian hospital wards can be a challenge. One such piece of equipment is the oxygen concentrator, necessary for treatment of respiratory disease, use with CPAP machines, and in the administration of surgical anesthesia. This device fills many roles in low-resource hospitals, but in many Malawian hospitals it is the most frequently malfunctioning piece of equipment. A survey administered to medical personnel and maintenance personnel in hospitals in Malawi’s Central and Southern Regions isolated some common causes of oxygen concentrator malfunction. Prominent among these were poor oxygen concentrator ventilation and the lack of consumable replacement parts such as the intake bacterial filter. A stand made from locally-sourced materials was developed to encourage better oxygen concentrator exhaust and raise the device out of dust and cleaning fluids on ward floors. Intake bacterial filter alternatives were researched, designed, constructed, and tested, manufactured from housing materials and filter media available in Malawi or continental Africa. A primary source of difficulty for low-resource hospitals is lack of autonomy, requiring aid from affluent nations to supply equipment and consumable materials. This work suggests that sustainable innovations, such as allowing consumables to be produced in-country, can replace aid with development and create more accessible materials to hospital maintenance personnel. Collaboration with material suppliers and engineers in Malawi can provide sustainable designs and systems to help hospitals access the supplies they need to service oxygen concentrators and other equipment. / Master of Science / The quality of healthcare in low-resource countries is often limited by the environment, lack of funds, staff availability, electricity availability, and more. In the words of a Malawian physician, medicine can feel like improvisation, wherein one must make due with available resources rather than desired resources. One prevalent problem among low-resource hospitals is the functionality and longevity of medical equipment. A large percentage of all medical equipment in Malawian hospitals is donated, resulting in a wide spectrum of models, necessary spare parts, and functionality. These machines can break quickly due to heavy use prior to donation, missing user and maintenance manuals, and a lack of replacement parts. Thus, finding necessary life-saving equipment in Malawian hospital wards can be a challenge. One such piece of equipment is the oxygen concentrator. This device fills many roles in low-resource hospitals, but in many Malawian hospitals it is the most frequently malfunctioning piece of equipment. A survey was used in hospitals in Malawi’s Central and Southern Regions to collect information on why oxygen concentrators malfunction. Common reported causes of malfunction were oxygen concentrators overheating due to clogged exhaust vents, and the unavailability of necessary disposable filters. A stand made from locally-available materials was developed to improve oxygen concentrator ventilation. Replaceable filter alternatives were researched, designed, constructed, and tested, made from housing materials and filter materials available in Malawi or continental Africa. A primary source of difficulty for low-resource hospitals is dependence on more developed nations for supplies and aid. This work suggests that designing materials from locally-available materials can lessen this dependency and make necessary medical materials more accessible. Collaboration with material suppliers and engineers in Malawi can provide sustainable designs and systems to help hospitals access the supplies they need to service oxygen concentrators and other equipment.

Heart failure is a cause of significant burden to both individuals and society. Individuals live with a disease where there is a decline in physical functioning, the experience of a range of symptoms including breathlessness and pain, frequent hospitalisations and death. The frequent hospital admissions that are usually precipitated by shortness of breath places an economic burden on the current health system. This burden of heart failure is expected to increase in the coming years due to factors such as the ageing population and improved survival from acute cardiac events. This current and predicted continuing burden has been recognised by the health system and has resulted in significant improvement in the pharmacotherapy and nonpharmacotherapy treatment of heart failure. Despite this improvement and with the exception of those few who receive cardiac transplantation, there is no cure for heart failure. Whist the advances in therapy have promoted significant improvements in heart failure management, symptoms including breathlessness (dyspnoea) remain a major issue. The Management of Dyspnoea in Advanced Heart Failure project explored and assessed the current therapeutic management of dyspnoea in advanced heart failure and examined two potential therapeutic options namely nebulised frusemide and long-term oxygen therapy. Following a comprehensive review of the nebulised frusemide literature, The Haemodynamic Effects of Nebulised Frusemide in Heart Failure study showed that nebulised frusemide did have an impact on the haemodynamic parameters of participants. Whilst many consider oxygen therapy as a common sense approach for breathlessness, the lack of scientific evidence for its use in chronic breathlessness with people who have normal or mildly low oxygen levels has prevented funding to supply oxygen therapy to this group of patients. The O2 Breathe Study is a palliative care study that is testing long-term home oxygen therapy versus medical air in patients who do meet the current funding arrangements. The analysis of the screening data showed that the symptom burden as a result of dyspnoea is similar to that seen in cancer and respiratory patients, and heart failure patients had lower levels of physical functioning than the respiratory group. Whilst the design of the studies in this thesis will not allow conclusions to be made regarding their efficacy for dyspnoea management in heart failure, they have provided preliminary data and hypotheses to be tested in the future. / Doctor of Philosophy (PhD)

Hyperbaric oxygen (HBO) therapy is the intermittent inhalation of 100% oxygen at a pressure greater than one atmosphere absolute. It is an effective treatment for various inflammatory conditions, including chronic wounds which are characterized by an excessive influx of neutrophils and their prolonged persistence at the wound site. Neutrophil apoptosis and clearance have been shown to be required for resolution of inflammation. The mechanisms by which HBO aids wound healing are well documented, but its effects on cellular inflammatory response are not well understood particularly with respect to neutrophils. The hypothesis presented in this thesis is that increased oxygenation via HBO assists chronic wound healing by enhancing non-inflammatory neutrophil defences and cell death through apoptosis. An investigation was carried out into the effects of HBO on neutrophil antimicrobial function and apoptosis using differentiated HL-60 cells as an in vitro neutrophil model. The data clearly showed that a single HBO treatment for 90 min caused an increase in the oxidative burst activity of neutrophil-like cells as shown by increased NBT staining, superoxide (cytochrome c reduction) and H2O2 production (Kruskal-Wallis, P < 0.05), and phagocytosis of Staphylococcus aureus. HBO treatment displayed a pro-apoptotic effect, enhancing caspase 3/7 activity both in the presence and absence of a TNF-α stimulus (Kruskal-Wallis, P < 0.05) and causing morphological changes (observed using Giemsa and SYBR® Safe staining) associated with apoptosis. Although no consistent pattern was observed, both hyperoxia and pressure alone seemed to contribute to both the increase in antimicrobial activity and the increase in apoptosis induced by HBO in these neutrophil-like cells (Chapters 4 and 5). HBO-enhanced neutrophil clearance by macrophages was investigated using bovine neutrophils and monocyte-derived macrophages (MDMФ). A single 90 min HBO exposure significantly increased the clearance of fresh and 22 h-aged neutrophils by MDMФ (two-way ANOVA, P < 0.05), suggesting an increase in phosphatidylserine (PS) exposure in apoptotic neutrophils after HBO treatment (Chapter 6). Importantly, a long-term repetitive exposure to HBO in patients with chronic wounds caused a significant decrease in the antioxidant enzyme defence system (one-way repeated measures ANOVA, P < 0.05), plasma TNF-α and IL-1β after 30 HBO sessions, with down regulation of expression of the anti-apoptotic factors, NF-B and Bcl-2 (Chapter 7). These findings may go some way towards explaining the effectiveness of HBO treatment not only for chronic wounds but also for other inflammatory conditions that may be affected by this treatment.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Thesis Ph. D.)(Chemical Engineering)--University of Pretoria, 2003. / Title from opening screen (viewed Oct. 06, 2004). Summaries in English and Afrikaans. Includes bibliographical references (leaves 144-151).