Ulm, Univ., Diss., 2008.

Thesis (Ph.D.) - James Cook University, 2005. / Typescript (photocopy) Bibliography: leaves 240-256.

Thesis (M.S. in Mechanical Engineering)--Vanderbilt University, Dec. 2006. / Title from title screen. Includes bibliographical references.

Thesis (Ph. D.)--Oregon State University, 2010. / Printout. Includes bibliographical references (leaves 89-93). Also available on the World Wide Web.

Restless legs syndrome (RLS) is a sensorimotor disorder that often starts at a young age and has a chronic progression throughout life. It has a very high incidence, affecting 10% of the general population. The majority of cases are familial and the genetic nature of the disorder has been demonstrated in twin studies. RLS segregates in an autosomal dominant way in the majority of families. This data has incited a search for genetic factors responsible for RLS using linkage as the approach. Dr. Rouleau's laboratory has one of the world's largest collections of RLS pedigrees. These families are mostly of French Canadian (FC) origin. / Using these families, two novel candidate loci, on chromosomes 16p and 20p, were discovered. Also, previously described candidate loci on chromosomes 9p and 14q were replicated in this cohort of families. / A duplication of a large part of a functional candidate gene in the locus on chromosome 20, Signal Regulatory Protein beta 1 (SIRPB1), was discovered in individuals affected with RLS from a FC pedigree, in which linkage to this locus was described. The duplication segregates with the disease status in the family, but its role in RLS pathogenesis has yet to be demonstrated. / No disease-causing mutations were discovered in the chromosome 16 locus. Analysis of several functional and positional candidate genes in previously described loci on chromosomes 12 and 14 did not reveal disease-causing mutations. / A follow up of these studies is necessary in order to confirm the implication of SIRPB1 in RLS pathogenesis, and to detect novel gene(s) whose deregulation leads to this disorder.

Chronic venous disease (CVD) of the lower limbs is a major problem in the western world with 1% of the adult population estimated to be affected at any one time. The clinical sequelae of CVD of the lower limbs range from oedema, haemosiderosis and pigmentation, to gross lipodermatosclerosis (LDS) and venous ulceration. The site most commonly affected is the gaiter area of the lower limb. The extent and severity of venous disease can be assessed by clinical and physiological methods which include duplex ultrasonography and plethysmography. Tissue oedema can be assessed by volumetric or circumferential measurements and venous ulcers may be quantified by area measurements and response to treatment in ulcer healing studies. In the vast majority of patients a spectrum of skin changes precedes venous ulceration. At present, there is no standardised objective method of assessing the degree of skin change in these patients, so that the response to treatment can be objectively monitored. I have developed a tissue tonometer and standardised the methodology for the objective assessment and quantification of the skin changes seen in patients. The tissue tonometer is a simple non-invasive instrument which uses a sensing device that detects the movements of a loaded plunger placed on the skin. The movement of the plunger is dependent on the mechanical properties of the skin and subcutaneous tissue. The instrument is positioned on the gaiter region of the leg with the subject in the supine position. The movement of the plunger into the tissues is recorded and analysed by a computer. The data obtained from the tonometer were analysed as distance and rate constant parameters. A simple mathematical model using spring and dashpot constants was also applied to see if it fitted the data. Skin compliance was investigated in normal control subjects and patients with varying severity of skin changes due to CVD, clinically classified according to the CEAP (Clinical, (A)Etiological, Anatomical and Pathophysiological) method. There was a significant reduction in skin compliance in patients with clinically severe LDS as compared to normal controls and patients with pigmentation alone or oedema without any clinical evidence of skin change. I further investigated the correlation between the recently introduced CEAP method of classification and scoring of chronic venous disease of the lower limbs with the tissue tonometry findings and parameters obtained with duplex ultrasonography, air plethysmography and photoplethysmography. Tissue tonometry provides a standardised objective means of assessing the severity of skin change in CVD which may prove to be useful in evaluating response to a particular treatment and comparing data from different centres. The deterioration of the venous physiology shown by blood flow measuring techniques correlates poorly with the clinical sequelae of venous disease, whether assessed by a trained observer or measured by the tonometer. Patients show a wide range of sensitivity to venous valvular incompetence, suggesting that factors related to the tissue response to venous hypertension are crucial in determining which patients develop venous ulceration.

Thesis (Ph.D.)--Arizona State University, 2008. / Includes bibliographical references.

No description available.

Introduction: Restless legs syndrome (RLS) is a common neurological disorder affecting 10% of the population. Most antidepressants exacerbate symptoms; however, correlational studies have noted symptom improvement with bupropion. The purpose of the current study was to examine whether, in a controlled study, bupropion would improve the symptoms of RLS, or at least not exacerbate them. Methods: This was a double-blinded, randomized controlled trial. Twenty-nine participants with moderate to severe RLS received 150 mg sustained-release bupropion once daily, and 31 control participants received a placebo. Participants were followed for 6 weeks and completed standardized tools, including the International Restless Legs Syndrome Study Group (IRLSSG) severity scale. Results: The primary outcome was change from baseline in IRLSSG severity score; lower scores were associated with improved symptoms. At 3 weeks, IRLSSG scores were 10.8 points lower in the bupropion group and 6.0 points lower in the placebo group (P = .016). At 6 weeks, IRLSSG scores were 10.4 points lower in the bupropion group and 7.6 points lower in the placebo group (P = .108). Bupropion was more effective than placebo in the treatment of RLS at 3 weeks; however, this difference was not statistically significant at 6 weeks. Conclusions: The data from our study suggest that bupropion does not exacerbate the symptoms of RLS and may be a reasonable choice if an antidepressant is needed in individuals with RLS. Larger studies that include titration of bupropion should be considered to determine if bupropion is appropriate for primary treatment of RLS, particularly considering the lower cost and favorable side effect profile compared with currently recommended first-line dopamine agonists.

No description available.