Thesis (Ph.D.)--University of Western Australia, 2005.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Spontaneously active primary cultures obtained from dissociated embryonic medial medulla tissue were grown on microelectrode arrays for investigating burst patterns and pharmacological responses of respiratory-related neurons. Multichannel burst rates and spike production were used as primary variables for analysis. Pacemaker-like neurons were identified by continued spiking under low Ca++/high Mg++conditions. The number of pacemakers increased with time under synaptic blocking medium. Sensitivity to CO2 levels was found in some neurons. Acetylcholine changed activity in a complex fashion. Curare, atropine and gallamine modified ACh effects. Eserine alone was ineffective, but potentiated ACh-induced responses. Norepinephrine caused channel-specific increases or decreases, whereas dopamine and serotonin had little effect at 30 μM. GABA and glycine stopped most spiking at 70 μM. Developmental changes in glycine sensitivity (increasing with age) were also observed. It is concluded that pacemaker and chemosensitive neurons develop in medial medulla cultures, and that these cultures are pharmacologically histiotypic.

Call number: LD2668 .T4 1978 C73 / Master of Science

Call number: LD2668 .T4 1979 E94 / Master of Science

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

Background: Cotton workers are highly exposed to organic dust. Inhalation of cotton based particulate has been associated with various respiratory symptoms and impaired lung function. This study investigates the respiratory health profile of textile mill workers in Nepal in relation to dust and endotoxin exposure. Methods: This study was conducted in four sectors (garment, carpet, weaving and recycling) of the textile industry in Kathmandu, Nepal. A total of 938 individuals completed a health questionnaire and performed spirometry. A subset of 384 workers performed cross-shift spirometry. Personal exposure to inhalable dust and airborne endotoxin was measured during a full-shift for a 114 workers. Results: Geometric mean concentrations of personal exposure to cotton dust and endotoxin were 0.81 mg/m3 and 2160 EU/m3 respectively. Overall prevalence of persistent cough, persistent phlegm, wheeze, breathlessness and chest tightness were 8.5%, 12.5%, 3.2%, 6.5%and 3.6% respectively. Symptoms were most common among the recyclers and less in the garment sector. Exposure to inhalable dust significantly predicted the symptoms of persistent cough and chest tightness. Significant cross-shift reduction in FEV1, FVC, and FEF25_75 were measured in the textile workers (p<0.001 for all); reductions being greater in the recyclers (-143 ml) and smallest in the garment workers (-38 ml) (p=0.012). Cross-shift reduction in FEV1 was significantly predicated by exposure to inhalable dust. Exposure to endotoxin did not correlate with any of the respiratory symptoms nor to lung function. Conclusion: The measured association between exposure to inhalable dust and reporting of respiratory symptoms and lung function suggests that despite high levels of endotoxin exposures, inhalable dust is the driver for these effects and attention should turn to what might be the toxic component in this dust other than endotoxin.

Hypoxia is a common feature of many respiratory disorders including acute severe asthma, chronic obstructive pulmonary disease and pneumonia. Hypoxia also occurs during sleep - disordered breathing in conditions such as sleep hypoventilation syndrome and sleep apnea. In most respiratory diseases hypoxia is coupled with increased respiratory load. Compensatory protective mechanisms are activated to oppose these impediments to respiration. However, hypoxia is associated with impaired neurocognitive function and recent studies have demonstrated that hypoxia suppresses respiratory load perception in healthy individuals and asthma patients. These recent findings raise the possibility that a variety of protective physiological reflex responses to increased respiratory load may be impaired during periods of hypoxia. The effects of hypoxia on several of these protective responses and possible mechanisms of respiratory sensory depression by hypoxia are explored in the experiments outlined in this thesis. In the first study, the respiratory related evoked potential ( RREP ) was used to investigate the mechanisms underlying hypoxia - induced suppression of respiratory load sensation in healthy individuals. As a positive control the effects of hypoxia on respiratory load perception to inspiratory resistive loads were also measured. The amplitude of the first and second positive peaks ( P1 and P2 ) of the RREP were significantly reduced during hypoxia. P1 is thought to reflect the arrival of the ascending respiratory signals to the somatosensory area of the cortex. The perceived magnitude of externally applied inspiratory resistive loads was also reduced during hypoxia. These data provide further support that hypoxia suppresses respiratory load perception and suggest that this is mediated, at least in part, by suppression of respiratory afferent information prior to its arrival at the cortex. In the second study, the effects of acute sustained hypoxia on the cough reflex threshold and cough tachyphylaxis to inhaled capsaicin were explored in healthy individuals. Acute sustained hypoxia suppressed cough reflex sensitivity to inhaled capsaicin. This finding raises the possibility that the cough reflex, important for protecting the lungs from inhalation or aspiration of potentially injurious substances and for clearing excess secretions, may be impaired during acute exacerbations of hypoxic - respiratory disease. In the third study, reflex responses of the genioglossus and scalene muscles to brief pulses of negative airway pressure were compared between hypoxia and normoxia during wake and sleep in healthy males in the supine position. Cortical RREPs to the same stimuli were also examined under these conditions. The genioglossus is the largest upper airway ( UA ) dilator muscle and can be reflexively augmented in response to negative UA pressure. A diminished response of this muscle during sleep has been postulated to be a contributing mechanism to obstructive sleep apnea ( OSA ) in individuals with an anatomically narrow UA. Cortical activation ( i.e. arousal ) to sudden airway narrowing in OSA is an important protective response to help restore ventilation during an obstructive event. In this study, genioglossus reflex responses to negative pressure pulse stimuli were maintained during mild overnight hypoxia. Conversely, reflex inhibition of the scalene muscle to the same stimuli was prolonged during hypoxia. In addition, a previously undescribed morphology of the genioglossus negative pressure reflex consisting of activation followed by suppression was observed with greater suppression during sleep than wake. The amplitude of the P2 component of the RREP was also significantly reduced during hypoxia. In summary, the potential mechanisms underlying hypoxia - induced suppression of respiratory load sensation and the effects of hypoxia on several protective respiratory responses have been investigated in healthy subjects. The potential implications of these findings for patients with hypoxic - respiratory disease are discussed. / Thesis (Ph.D.)--School of Molecular and Biomedical Science, 2006.