Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 111-118).

Thesis (M.S.)--University of Alabama at Birmingham, 2009. / Title from PDF title page (viewed on Sept. 3, 2009). Includes bibliographical references (p. 50-67).

Lysosomal storage disorders (LSDs) are caused by defective lysosomal degradation of macromolecules resulting in accumulation of substrates in various tissues. This gradually leads to organ dysfunction and the classical clinical presentation with multisystem involvement. Historically the management of LSDs was confined to symptomatic treatment only. More recently other therapies have become available. Treatment options include cellular therapy in the form of Haemopoietic Stem Cell Transplant (HSCT), Enzyme Replacement Therapy (ERT), Substrate Reduction Therapy (SRT), Chaperone Mediated Therapy (CMT) and gene therapy. Whilst HSCT and ERT are established strategies in clinical practice for some LSDs, others are still in the development phase. The easy accessibility of ERT in the developed world (despite a high cost burden of approximately £144,000 per patient per annum in the UK), fewer risks associated with its administration and good metabolic and clinical outcome, have made ERT the treatment of choice for a number of LSDs. In recent years immune response has been identified as a significant factor in attenuating or nullifying the response to ERT. Despite recognition of this problem, there is a lack of reliable diagnostic tools to test and evaluate the antibody responses in the centres delivering ERT and far too little attention has been focused on development, optimisation and standardization of immune assays. In this project, IgG ELISA and two different functional enzyme inhibition assays (catalytic inhibition and cellular uptake inhibition) were developed and optimized. The immune response to ERT was then studied in recipients of ERT in MPSI, MPSVI and Pome disease. Our practice of delivering ERT in recipients of allogeneic HSCT prior to transplant provided us with an opportunity to study the immune response in MPSIH patients during ERT and following HSCT. We demonstrated functionally active antibodies in long term recipients of ERT in MPSI and Pompe disease. Allo-immune response in MPSVI did not inhibit the delivered enzyme therapy. A high titre inhibitory immune response was detected in the majority of MPSIH patients after exposure to ERT. This immune response was abrogated by allogeneic HSCT rendering these patients tolerant to replaced enzyme, confirming HSCT as an effective immune tolerance induction mechanism.

Orientador: Yasmin Rodarte Carvalho / Banca: Juliana Mazzonetto Teófilo / Banca: Ana Lia Anbinder / Banca: Adriana Aigotti Haberbeck Brandão / Banca: Horácio Faig Leite / Abstract: Due to the adverse effects of estrogen, new therapies have been proposed, such as soy isoflavones. However, their effects on bone repair and uterus epithelium remain unclear. The aim of this work was to study the acute effects of ovariectomy and treatment with estrogen and soy isoflavones, isolated or in association, on rat bone repair and uterus epithelium. 120 rats were used; 96 ovariectomized and 24 Sham-operated (SHAM). The ovariectomized rats were dibided into 4 groups, receiving orally: 1 mg/kg/day of 17 'beta'-estradiol valerate(OVZ-E); 15mg/kg/day of isoflavones (OVZ-I); associated treatments (OVZ-A); and vehile (OVZ). SHAM rats received vehicle. Treatment began on the ovariectomy day. The lower first molar was removed on both sides 15 days after ovariectomy. The rats received the treatment until sacrificed, which occurred at seven, 21 and 45 days after dental extraction. The uterus was submitted to histological analyses and the mandible to histological, histomorphometric, backscattered electron microscopy (BSE) and immunohistochemistry analyses. Concerning bone repair, no difference was observed in trabecular volume between the OVZ and SHAM groups for each period. Histological analysis and BSE revealed changes in bone microarchitecture after 45 days. Verification showed that the SHAM group presented a higher mean osteoid volume at seven days compared to the OVZ and OVZ-E groups and that the OVZ-A group showed the highest mean for this period. The number of mast cells tended to be higher in the OVZ group at 45 days. Strong expression of TGF-'beta' was observed at seven days, which diminished over time. The OVZ-E group presented the lowest mineral apposition rate at seven days. No difference was observed for the remaining periods. The SHAM, OVZ-E and OVZ-A... / Doutor

M.Tech. (Homoeopathy) / Menopause is the natural or iatrogenic termination of menstrual periods as a result of decreasing ovarian function. Natural menopause begins when menstrual periods have been absent for one year (Beers et al., 2006). The Climacteric is the period which encompasses the transition from the reproductive state to the non-reproductive state. Menopause, therefore, is a specific event that takes place during the climacteric (Collins et al., 2010). The symptoms are usually treated conventionally with Hormonal Replacement Therapy (HRT), but a large number of adverse side-effects are associated with its use (Harvey and Champe., 2009). De Schepper (2001) states that the true Homoeopathic Similimum strengthens a person’s vital force which results in the improvement of disease symptoms. Barton (2008) states that it is very difficult to accurately find the Homoeopathic Similimum for each case; therefore, Grant Bentley and his team have worked to develop a system of analysis, to facilitate the identification of the Similimum for each case. The Grant Bentley Method requires photography of the face and analysis of the facial features necessary to ascertain the miasmatic category into which the participant falls (Barton, 2008). There is no research verifying the effectiveness of this method in the treatment of climacteric symptoms. The aim of the study is to evaluate the effect of the Homoeopathic Similimum, using the Grant Bentley-method, on Climacteric symptoms. The study was carried out in the form of case studies over a twelve week period. Eleven females, between the ages of forty and sixty-five years, who were experiencing climacteric symptoms and who met the inclusion and exclusion criteria were recruited, using purposive sampling, by placing advertisements (Appendix A) in local newspapers, pharmacies and medical practices in the Vanderbijlpark area and at the Doornfontein Campus of the University of Johannesburg. The process of the study was explained to the participants and consent forms were signed (Appendix C and D). Participants, with the researcher’s help, completed a Suitability Criteria Questionnaire (Appendix B). During the first consultation the Menopause Rating Scale (MRS) (Appendix E and F) was completed and evaluated (Appendix G). The Homoeopathic case studies took the form of one-on-one conversations in order to complete a Case Taking Form (Appendix I) and incorporated a relevant physical examination and a Grant Bentley Evaluation of each participant’s facial features from which their miasmatic categories were determined (Appendix H). The participant’s case information was examined in accordance with the principles of homoeopathic classical prescribing, based on the entirety of symptoms. From this process the similimum was determined and given according to homoeopathic principles...

Although many women find relief from menopause through hormone therapy (HT), current guidelines recommend that HT be used only for short-term relief of symptoms. Women who attempt to stop HT often encounter troublesome recurrent symptoms leading to a diminished quality of life (QoL); 25% of women who discontinue eventually resume HT. Unfortunately, there is little information for women and their health care providers as to the best way to discontinue HT or how to prepare and guide women through this process. An in-depth description of women‘s experiences during HT discontinuation and the factors influencing recurrent symptoms, QoL and discontinuation outcome would provide knowledge to develop much needed counseling and support interventions. The purpose of this study was to explore women‘s experiences discontinuing hormone therapy for menopause. This Internet-based mixed-methods study used a dominant Qualitative Descriptive design with embedded quantitative QoL measurements. Participants completed the quantitative questionnaires online while open-ended questions were completed either online or by telephone. Interview data were analyzed through Qualitative Content Analysis; descriptive statistics were used to explore the quantitative measures. Participants were stratified by discontinuation status for comparison of variations in discontinuation experiences, QoL and influencing factors. Thirty-four women (20 stopped, 9 resumed, 4 tapering) were enrolled. One overarching theme--'a solitary journey'--emerged: although all women embarked on this journey, each woman traveled her own path. Two subthemes--'burden and interference' and 'appraising risk'--encompassed the symptom factors (severity, interference and sensitivity) that influenced women's experiences and the manner in which women evaluated their options. Other influencing factors included: readiness viii and reasons for stopping HT, beliefs about menopause and roles. QoL was strongly connected to symptoms for many but not all women. Information from health care providers was inconsistent; women desired more support from providers and other women. The rich description of women's experiences stopping HT highlights the need for providers to assess women's sensitivity to symptoms and readiness to discontinue to determine which women might benefit from more support. Greater health literacy would enhance women's understanding of HT risks. More research is needed on symptom clusters and interference and strategies for minimizing their impact.

No description available.

Treatment studies provide minimal support for nicotine replacement therapy (NRT) with youth; however, survey studies suggest that adolescents use NRT, and may engage in inappropriate use. The current study sought to examine patterns of NRT use and risk factors for use to further aid smoking cessation efforts including prevention of potential misuse. In-school surveys assessing socio-demographic and behavioral factors associated with NRT use, gum or patch, were completed by 4078, predominantly African American, high school students. Approximately 5% of students reported former or current use of NRT products: 42% gum, 29% patch, and 29% both gum and patch. Among smokers, 5.4% reported use of both NRT gum and patch, with exclusive use of gum twice as likely as exclusive use of the patch. Those with high-risk-taking attitudes were more likely than low-risk takers (3% vs. 1%) to report use of both products, with exclusive gum use more prevalent than patch use. A cumulative logit model revealed males, risk takers, and/or smokers were at greatest odds for NRT use. Among this adolescent sample, NRT gum was used more often than the patch. Adolescent males, risk takers, and/or smokers appear more likely to use NRT (gum and/or patch) compared to their counterparts, despite limited empirical support for effective use of these products as cessation aids among adolescents. Smoking cessation and prevention programs may emphasize appropriate NRT use, specifically within these populations.

No description available.

Smoking combustible cigarettes is the major cause of disease and death among adults living in the United States (U.S.). In fact, smoking combustible cigarettes causes nearly half a million premature deaths among U.S. adults every year.1–4 It is estimated that over 14% (equating to 34 million persons) of U.S. adults smoke cigarettes currently.2,5 This is a substantial decrease from 1965 when it was estimated that more than 42% of U.S. adults smoked cigarettes.1 This is partly attributed to the well-established evidence that smoking cigarettes causes harm to almost every human organ system5 and is associated with an elevated risk of developing cancer6, cardiovascular disease 7, pulmonary disease and respiratory illnesses.8–10 Despite the well-established health consequences of smoking cigarettes, millions of people are still smoking, which alone suggests that nicotine (the primary constituent of cigarettes) is highly addictive.3 Thankfully, smoking cessation by means of pharmacological treatments has been shown to help smokers overcome nicotine addiction. A review of the research on the efficacy of varenicline (Chantix) and Nicotine Replacement Therapy (NRT), two of the most commonly used smoking cessation treatments, reveals that both treatments increase long-term smoking abstinence rates with odds ratios of 3.85 for varenicline and 1.74 for NRT when compared to placebo.11–14 Even more, both drugs appear to be generally well-tolerated, with no known life-threatening side effects when compared to placebo. Research shows that the most common side effects for varenicline are nausea, insomnia, gastrointestinal effects, headache and abnormal dreams.11,15 The most common side effects for NRT appear to be skin irritation, insomnia, headache, nausea/vomiting and cough.11,15 Ultimately, both varenicline and NRT appear to be strong options for achieving smoking abstinence both with respect to overall efficacy and tolerability.