Introduction: Nursing clinicians are primarily responsible for the monitoring and treatment of increased body temperature. The body temperature of patients during their acute care hospital stay is measured at regular repeated intervals. In the event a patient is assessed with an elevated temperature, a multitude of decisions are required. The action of instigating temperature reducing strategies is based upon the assumption that elevated temperature is harmful and that the strategy employed will have some beneficial effect. Background and Significance: The potential harmful effects of increased body temperature (fever, hyperthermia) following neurological insult are well recognised. Although few studies have investigated this phenomenon in the diagnostic population of non-traumatic subarachnoid haemorrhage, it has been demonstrated that increased body temperature occurs in 41 to 72% of patients with poor clinical outcome. However, in the Australian context the frequency, or other characteristics of increased body temperature, as well as the association between increased body temperature with poor clinical outcome has not been established. Design: This study used a correlational study design to: describe the frequency, duration and timing of increased body temperature; determine the association between increased body temperature and clinical outcome; and describe the clinical interventions used to manage increased body temperature in patients with non-traumatic subarachnoid haemorrhage. A retrospective clinical chart audit was conducted on 43 patients who met the inclusion criteria. Findings: The major findings of this study were: increased body temperature occurred frequently; persisted for a long time; and onset did not occur until 20 hours after primary insult; increased body temperature was associated with death or dependent outcome; and no intervention was recorded in many instances. Conclusion: This study has quantified in a non-traumatic subarachnoid haemorrhage patient population the characteristics of increased body temperature, established an association between increased body temperature with death or dependent outcome and described the current management of elevated temperatures in the Australian context to improve nursing practice, education and research.

Core temperature (Tc) regulation is fundamental to mammalian survival, since hypothermia (Tc ≤ 35°C) and hyperthermia (Tc ≥ 40°C) are major risk factors for health and wellbeing. The purpose of this thesis was to determine if acetaminophen, an analgesic and antipyretic drug, increased the onset of hypothermia or hyperthermia during passive cold and heat stress, respectively. It was later investigated if acetaminophen induced inhibition of cyclooxygenase mediated these side-effects. In Study 1a, the plasma acetaminophen response to a dose of 20 mg·kg-1 of lean body mass was determined through enzyme linked immunosorbent assay. In Study 1b, the effect of acetaminophen administration on internal temperature (rectal; Tre) during a passive 2-hour mild cold (20°C, 40% relative humidity) exposure was examined. Study 1a showed that the plasma response was homogenous between subjects, reaching peak concentrations between 80-100 minutes (14 ± 4 μg·ml-1). In Study 1b, acetaminophen reduced Tre in all participants compared with baseline, and the average peak reduction was 0.19 ± 0.09°C. In contrast, Tre remained stable when participants ingested a sugar placebo. Study 1 is the first experiment which confirms a hypothermic side-effect of acetaminophen in healthy humans. Study 2 investigated whether acetaminophen augmented the rate of Tre rise during exposure to passive dry (45°C, 30% r.h.) and humid (45°C, 70% r.h.) heat stress for 2-hours and 45-minutes, respectively. This study showed that the rate of Tre rise in the dry (0.005 vs 0.006°C∙min-1) and humid (0.023 vs 0.021 °C∙min-1) conditions were similar between the acetaminophen and placebo trials (p > 0.05). Study 2 is the first experiment which confirms acetaminophen has no meaningful effect on thermoregulation during passive dry or humid heat exposure. Study 3 determined how the hypothermic effect of acetaminophen changes during exposure to a thermoneutral (25°C, 40% r.h.) and cold (10°C, 40% r.h.) environment for 2-hours. In summary, there was no hypothermic effect of acetaminophen in a thermoneutral environment (p > 0.05), whereas Tre fell by 0.40 ± 0.15°C compared with baseline during cold stress (p < 0.05). Compared with the placebo, Tre was ~0.35°C lower at 120 minutes, but was significantly lower from 70-minutes. Study 3 confirmed that there is a relationship between the level of cold stress and magnitude of the hypothermic effect of acetaminophen. Study 4 determined whether ibuprofen (400 mg), a cyclooxygenase inhibitor, reduced Tre during 2-hour passive cold stress (10°C, 40% r.h.) to a level comparable with acetaminophen. Ibuprofen administration did not influence Tre, vastus medialis shivering, or energy expenditure compared with a placebo throughout the cold exposure (p > 0.05). Taken together, this renders it unlikely that cyclooxygenase activity is required for thermogenesis induced by skin cooling. Study 4 provides evidence that acetaminophen induced hypothermia is not exclusively mediated by cyclooxygenase inhibition. In Summary, this series of experiments has shown that acetaminophen has a hypothermic side effect in healthy humans, which is amplified during acute cold stress. Ibuprofen had no such effect on thermoregulation during cold exposure, so it is unlikely that cyclooxygenase inhibition mediates the hypothermic side-effect of acetaminophen.

The deposition of ultrasonic energy in tissue can cause tissue damage due to local heating. For pressures above a critical threshold, cavitation will occur in tissue and bubbles will be created. These oscillating bubbles can induce a much larger thermal energy deposition in the local region. Traditionally, clinicians and researchers have not exploited this bubble-enhanced heating since cavitation behavior is erratic and very difficult to control. The present work is an attempt to control and utilize this bubble-enhanced heating. First, by applying appropriate bubble dynamic models, limits on the asymptotic bubble size distribution are obtained for different driving pressures at 1 MHz. The size distributions are bounded by two thresholds: the bubble shape instability threshold and the rectified diffusion threshold. The growth rate of bubbles in this region is also given, and the resulting time evolution of the heating in a given insonation scenario is modeled. In addition, some experimental results have been obtained to investigate the bubble-enhanced heating in an agar and graphite based tissue- mimicking material. Heating as a function of dissolved gas concentrations in the tissue phantom is investigated. Bubble-based contrast agents are introduced to investigate the effect on the bubble-enhanced heating, and to control the initial bubble size distribution. The mechanisms of cavitation-related bubble heating are investigated, and a heating model is established using our understanding of the bubble dynamics. By fitting appropriate bubble densities in the ultrasound field, the peak temperature changes are simulated. The results for required bubble density are given. Finally, a simple bubbly liquid model is presented to estimate the shielding effects which may be important even for low void fraction during high intensity focused ultrasound (HIFU) treatment.

A complete understanding of high-intensity focused ultrasound-induced temperature changes in tissue requires insight into all potential mechanisms for heat deposition. Applications of therapeutic ultrasound often utilize acoustic pressures capable of producing cavitation activity. Recognizing the ability of bubbles to transfer acoustic energy into heat generation, a study of the role bubbles play in tissue hyperthermia becomes necessary. These bubbles are typically less than 50μm. This dissertation examines the contribution of bubbles and their motion to an enhanced heating effect observed in a tissue-mimicking phantom. A series of experiments established a relationship between bubble activity and an enhanced temperature rise in the phantom by simultaneously measuring both the temperature change and acoustic emissions from bubbles. It was found that a strong correlation exists between the onset of the enhanced heating effect and observable cavitation activity. In addition, the likelihood of observing the enhanced heating effect was largely unaffected by the insonation duration for all but the shortest of insonation times, 0.1 seconds. Numerical simulations were used investigate the relative importance of two candidate mechanisms for heat deposition from bubbles as a means to quantify the number of bubbles required to produce the enhanced temperature rise. The energy deposition from viscous dissipation and the absorption of radiated sound from bubbles were considered as a function of the bubble size and the viscosity of the surrounding medium. Although both mechanisms were capable of producing the level of energy required for the enhanced heating effect, it was found that inertial cavitation, associated with high acoustic radiation and low viscous dissipation, coincided with the the nature of the cavitation best detected by the experimental system. The number of bubbles required to account for the enhanced heating effect was determined through the numerical study to be on the order of 150 or less.

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No description available.

In treating cancer with hyperthermia, an understanding of the heat losses associated with the presence of a large functioning blood vessel in or proximal to a treatment area is needed in order to optimize any protocol. A three-dimensional computer model based on the Bioheat transfer equation (BHTE) has been developed to account for temperature changes in and around functioning blood vessels during laser-induced hyperthermia. The light source is modelled using an approximation to the transport theory solution for an isotropic point source in an infinite homogeneous tissue medium with anistropic scattering. The derived BHTE's for tissue, vessel and blood are solved for temperature using the implicit finite differences method. The validity of the model was tested by comparing predicted temperatures to measured temperatures from a series of dynamic phantom studies using two vessel diameters and three flow rates. Large experimental temperature variations were observed and increased proportionally with increasing thermal gradients. The model consistently over-estimates (~ 1-2C) absolute temperatures close to the source and under-estimates (~ 1-2C) them far from the source. This could be due to uncertainties associated with the estimated thermal conductivity and measured optical properties of the tissue material. Both model and experiments show a small convective heat loss due to the presence of a blood vessel. The model predicts that at high flow rates, temperature reductions of 2C or greater are limited to distances less than 0.3 cm from the surface of a 0.144 cm (outer diameter) vessel and less than 0.8 cm from the surface of a 0.40 cm vessel. The vessel has a negligible effect on temperatures at distances greater than ~ 1.75 cm. The predicted temperature change due to blood flow and the measured change agree to within experimental errors. There was better agreement with the larger diameter vessel. / Thesis / Master of Science (MS)

Shallow light penetration in tissue has been a technical barrier to the development of photothermal therapies for cancers in the epithelial tissues and skin. This problem can potentially be solved by utilizing minimally invasive probes to deliver light directly to target areas potentially > 2 mm deep within tissue. To develop this solution, fiber optic microneedles capable of delivering light for therapy were manufactured. We have manufactured fiberoptic microneedles by tapering silica-based optical fibers employing a melt-drawing process. These fiberoptic microneedles were 35 to 139 microns in diameter and 3 mm long. Some of the microneedles were manufactured to have sharper tips (tip diameter < 8 microns) by changing the heat source during the melt-drawing process. All of the microneedles were individually inserted into ex vivo porcine skin samples to demonstrate the feasibility of their application in human tissues. Skin penetration experiments showed that sharp fiber optic microneedles with a minimum average diameter of 73 microns and a maximum tip diameter of 8 microns were able to penetrate skin without buckling. Flat microneedles, which had larger tip diameters, required a minimum average diameter of 125 microns in order to penetrate through porcine skin samples. Force versus displacement plots showed that a sharp tip on a fiber optic microneedle decreased the skin's resistance during insertion. Also, the force acting on a sharp microneedle increased more steadily compared with a microneedle with a flat tip. Melt-drawn fiberoptic microneedles provided a means to mechanically penetrate dermal tissue and deliver light directly into a localized target area. We also described an alternate fiberoptic microneedle design with the capability of delivering more diffuse, but therapeutically useful photothermal energy using hydrofluoric acid etching of optical fibers. Microneedles etched for 10, 30, and 50 minutes, and an optical fiber control was compared for their ability to deliver diffuse light using three techniques. First, red light delivery from the microneedles was evaluated by imaging the reflectance of the light from a white paper. Second, spatial temperature distribution of the paper in response to near-IR light (1,064 nm, 1 W, CW) was recorded using infrared thermography. Third, ex vivo adipose tissue response during 1,064 nm, (5 W, CW) irradiation was recorded with bright field microscopy. Increasing etching time decreased microneedle diameter (from 125 to 33 microns), resulting in increased uniformity of red and 1,064 nm light delivery along the microneedle axis. For equivalent total energy delivery, microneedles with smaller diameters reduced carbonization in the adipose tissue experiments. However, thin fiberoptic microneedles designed to minimize tissue disruption and deliver diffuse therapeutic light are limited in their possible clinical application due to a lack of mechanical strength. Fiberoptic microneedles have been embedded in an elastomeric support medium (polydimethylsiloxane, PDMS) to mitigate this issue. The critical buckling force of silica microneedles with 55, 70, and 110 microns diameters and 3 mm length were measured with and without the elastomeric support in place (N = 5). Average increases in the mechanical strength for microneedles of 55, 70, and 110 microns diameters were measured to be 610%, 290%, and 33%, respectively. Aided by mechanical strengthening through an elastomeric support, microneedles with 55 microns diameter were able to repeatedly penetrate ex vivo porcine skin. / Ph. D.

Hyperthermia can occur in lungs and airways during both physiological and pathophysiological conditions. A previous study carried out in our laboratory showed that hyperthermia activates and sensitizes vagal bronchopulmonary Cfiber afferents, whether this effect is through a direct action of hyperthermia on sensory nerves is not known. This dissertation study was aimed to investigate the thermal-sensitivity of pulmonary sensory neurons, and the roles of thermalsensitive transient receptor potential vanilloid (TRPV) channels. Whole-cell patch-clamp recordings of neurons isolated from nodose/jugular ganglia were applied in the study. Results of this study showed that hyperthermia directly activates pulmonary sensory neurons, and this effect is partially mediated through the TRPV subtype 1 (TRPV1) channel as well as other thermal-sensitive TRPV (2–4) channels. In addition, hyperthermia exerts potentiating effects on responses of pulmonary sensory neurons to TRPV1 activators, but not to non- TRPV1 activators. Furthermore, results obtained in the study of TRPV1-null mice revealed that TRPV1 plays a dominant role in mediating the potentiating effect of hyperthermia on pulmonary sensory neurons, but is only partially involved in the direct activation of these sensory neurons by increasing temperature. These results suggested that the thermal-sensitivity of pulmonary sensory neurons is dependent upon the function of the TRPV1 channel, and TRPV1-mediated sensitization of these sensory neurons may contribute to airway hyperreactivity and augmented reflex responses under hyperthermic conditions.

Basic in vitro cell experiments were conducted on the P388 mouse leukaemia cell line to determine whether a supra-additive cell killing effect from combining hyperthermia with ionising radiation exists in the case of leukaemia. Methods were established to measure the cell kill, using a Coulter counter, from hyperthermia alone, radiation alone and several combined regimes. The cell kill from hyperthermia, in the range of 38-50 degrees for 30 minutes, 1 hour, 2 hours and 3 hours, and radiation, for 1, 3, 5, 9, 11 and 15 Gy was investigated. The approach used had various limitations, such as the underestimation of cell kill. Consistent trends, however, were found for the hyperthermia and radiation data, in accordance with the literature, which killed cells in a predictable manner. Subsequently, after other preliminary combined experiments were completed, the cell kill from both 5 and 11 Gy combined with hyperthermia at 43, 45 and 47 degrees for 2 hours were investigated. 5 Gy in combination with all levels of hyperthermia resulted in a direct additive cell killing effect. This, however, was not observed for 11 Gy in which a diminished effect was found. The overall level of cell kill from 5 Gy combined with hyperthermia was found to be equal, in the case of 43 degrees, or higher, as for 45 and 47 degrees, to that of those combined with 11 Gy. A supra-additive effect was not observed.