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Glucose is the primary metabolic signal reflecting the current energy state of the body. Glucose influences the excitability of neurons in the area postrema (AP), a circumventricular organ (CVO), prompting my interest in investigating whether the subfornical organ (SFO), another sensory CVO can also detect glucose. Using patch-clamp electrophysiology, we investigated the influence of changing glucose concentrations on the excitability of SFO neurons. In dissociated SFO neurons, altering the bath concentration of glucose (1mM, 5mM, 10mM) influenced the excitability of 49% of neurons tested (n=67). Glucose-inhibited (GI, hyperpolarized by increased glucose or depolarized by decreased glucose) and glucose-excited (GE, depolarized by increased glucose or hyperpolarized by decreased glucose) neurons were observed. GI neurons (27%, n=18) depolarized in response to decreased glucose (n=10, mean 4.6 ± 1.0 mV) or hyperpolarized in response to increased glucose (n=8, mean -4.4 ± 0.8 mV). In contrast, GE neurons (22%, n=15) depolarized in response to increased glucose (n=9, mean 6.4 ± 0.4) or hyperpolarized in response to decreased glucose (n=6, mean -4.8 ± 0.6 mV). These data show that glucose acts on a subpopulation of SFO neurons to produce both excitatory and inhibitory actions. Using voltage-clamp recordings two groups of SFO neurons were identified: those producing an outward current (GI) and those producing an inward current (GE) in response to increasing concentrations of glucose from 1 to 10 mM (n=23). The mean glucose-induced inward current had a reversal potential of -24 ± 12 mV (mean input resistance 2.0 ± 0.4 GΩ, n= 5), suggesting it may be mediated by a NSCC. The mean glucose-induced outward current (mean input resistance 1.7 ± 0.3 GΩ, n=7) had a mean reversal potential of -78 mV ± 1.2 mV (n = 5), suggesting it may be mediated by an activation of either K+ or Cl-current (ECl = -67 mV, EK = -89 mV). The SFO has projections to the PVN, a regulator of energy balance. I investigated the effects of increasing concentrations of glucose (1 to 10 mM) on the membrane potential of dissociated SFO neurons projecting to the PVN. Thirty percent of SFO-PVN neurons tested (n=10) responded with membrane hyperpolarizations (mean -4.2 ± 0.8 mV, n=3) suggesting a proportion of these cells are GI neurons. These data indicate that SFO neurons are glucose-responsive, which supports a role for the SFO as a regulator of energy balance. / Thesis (Master, Physiology) -- Queen's University, 2009-09-24 20:20:33.319

The investigation and management of patients with life threatening haemoptysis is a common clinical problem in South African Hospitals. Establishing the aetiology and origin of the haemorrhage and treating these patients is both difficult and expensive in terms of human and financial resources. The purpose of this study was to identify common local aetiologies for severe haemoptysis, review the investigation and treatment of these patients at Wentworth Hospital, Durban and to formulate a plan of management. Retrospective and prospective studies of consecutive patients treated at Wentworth Hospital were performed. In the prospective study a new embolic material gelatin linked acryl microspheres (embospheres) was used for bronchial artery embolization (BAE). The study demonstrated a change in the spectrum of aetiologies of haemoptysis, from bronchiectasis following tuberculosis to destructive pneumonias. The chest radiograph was always the initial imaging investigation but was found to be inaccurate in detecting the origin of the bleeding. High resolution computed tomography of the lungs (HRCT) was the single best investigation to detect the cause and origin of the haemoptysis. HRCT detected focal bronchiectasis and intracavitatory aspergillomas that were undetected on the chest radiograph. Pleural thickening detected on CT was a good indicator of the presence of transpleural collaterals. The major limitation with HRCT was that it could not be performed if the patient was too dyspnoeic to cooperate during the scan. The role of bronchoscopy appears limited in patients with severe haemoptysis to those patients who are potential surgical candidates. I found that bronchoscopy was not accurate in detecting the source of bleeding in the few patients in which it was performed. Bronchial arteriography remains the gold standard in the detecting the source of haemorrhage. Bleeding sites were detected on angiography in the presence of focal hypervascularity, neovascularity and the presence of broncho-pulmonary shunts. Bronchial arteries were hypertrophied in bronchiectasis but were normal in size in some patients who had acute pneumonias. Bronchial artery embolization was the treatment of choice for severe haemoptysis in the patients studied. The use of gelatin cross linked micro spheres has significantly improved the initial success rate following the procedure with less complications compared to the use of polyvinyl alcohol particles (PVA). It is important to identify systemic transpleural collaterals at arteriography and to embolize them to reduce recurrent haemoptysis. Patients with aspergillomas responded well to embolization. Recurrent haemoptysis remains the major limitation of BAE but is reduced with the use of micro spheres as embolic agents and thorough embolization of systemic collaterals on the affected side. Surgical resection was an option for a limited number of patients with focal disease in one lung and good respiratory reserve. The major limitation of the study was the absence of long term follow up to detect those patients with late recurrent haemoptysis. / Thesis (D. Med.)-University of Natal, Durban, 2003.

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