The general aim of this thesis is to investigate small fiber neuropathy in sarcoidosis and to asses whether ARA290 is a possible new agent to treat the neuropathic complaints in sarcoidosis... Show moreThe general aim of this thesis is to investigate small fiber neuropathy in sarcoidosis and to asses whether ARA290 is a possible new agent to treat the neuropathic complaints in sarcoidosis population. The results of the various ARA290 trials in painful sarcoidosis are discussed. Painful neuropathy is common, difficult to treat complication.The limited efficacy of current treatment options dictates a rationalized design of novel compounds. ARA290 treatment was consistently associated with a significant improvement of neuropathic pain symptoms in sarcoidosis patients, evidenced by a decrease in pain scores on validated questionnaires. Moreover,ARA290 treatment resulted in significant increases in corneal nerve fibers, improved sensory pain thresholds,improved quality of life and physical functioning. Given the excellent safety profile while reducing neuropathy symptoms,the prospects of ARA290 treatment in sarcoidosis related neuropathy seem promising.The long lasting beneficial effects of ARA290 on both pain related and non pain related symptoms in sarcoidosis patients prompt additional studies on potential disease modifying properties of ARA290. The data collected so far suggest that ARA290 will be equally effective in SFN associated with other syndromes, including diabetes mellitus. Show less
Heart failure is a global epidemic, and despite significant advances in specific disease-directed therapies and interventions over the past decade, outcomes following a diagnosis of clinically... Show moreHeart failure is a global epidemic, and despite significant advances in specific disease-directed therapies and interventions over the past decade, outcomes following a diagnosis of clinically apparent cardiac failure remain suboptimal. Patients with heart failure are typically treated according to how they are classified by one single parameter from echocardiography (heart ultrasound) known as __ejection fraction,__ which describes how strongly their heart is pumping with each heartbeat. However, the limitations of this measure as an absolute marker of the presence or absence of heart muscle dysfunction, the precursor of clinical heart failure, is being increasingly recognized. This thesis investigates newer, more sensitive imaging techniques using advanced ultrasound software that enable the measurement of myocardial mechanics, which provide a more direct assessment of the pumping ability, or contractility, of the muscle fibers in the heart. The aim of the present thesis was to explore the use of myocardial mechanics across the spectrum of heart failure, from identifying earlier covert abnormalities in heart function within patients at risk of heart disease but who have not yet manifested the disease, to estimating the burden of disease and prognosis in those with established dysfunction due to coronary artery disease, the most common cause of heart failure worldwide. In the clinical research settings studied, assessment of intrinsic rather than surrogate heart muscle contractility using these newer techniques succeeded in facilitating 1) earlier identification of subclinical (not yet apparent) disease in sarcoidosis, an important multi-systemic disease which causes heart failure, and 2) incremental risk stratification in patients with established myocardial dysfunction due to coronary artery disease. It is hoped these insights will ultimately lead to improved detection and prognosis for patients with all stages of cardiac muscle dysfunction. Show less
