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Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 7 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 5 uppsatser.

Thesis (Ph.D.)--University of Western Australia, 2006.

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 67-72).

Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2007. / Bellamkonda, Ravi, Committee Member ; LaPlaca, Michelle, Committee Chair ; Stein, Donald, Committee Member ; Garca̕, Andrš, Committee Member ; Archer, David, Committee Member ; Borlongan, Cesario, Committee Member.

Current treatments for peripheral arterial occlusive disease (PAOD) have limited success, so there is a need to develop more effective treatments. Because patients with native collaterals have a better prognosis, promoting collateral arteriogenesis is a potential PAOD treatment. Additionally, female PAOD patients have a worse response to treatment and a worse prognosis compared to males, which could be due to impaired collateralization. Cell transplantation is a potential treatment option to promote collateral arteriogenesis. Bone marrow derived stem cells are the main cell type that has been investigated, but they have had limited clinical success. Delivering a stem cell type native to the tissue like myogenic stem cells could have improved outcomes. In this study, the lateral spinotrapezius feed artery was ligated in male and female Balb/C mice to induce collateral capillary arteriogenesis, and 7 days post ligation ­­­­arterialized collateral capillary (ACC) number and diameter were determined. There were no differences between sexes, which could be because young, healthy mice were used in this study rather than aged and diseased models. Because we observed no sex differences, we then assessed the effect of myogenic cell transplantation in male mice only. Immediately following ligation of the spinotrapezius feed artery, mice were treated with myogenic cells, thrombin, or vehicle, and 7 days post ligation ACC number and diameter were determined. Thrombin increased ACC number, but myogenic cells had no effect. However, myogenic cells increased ACC diameter, and both myogenic cells and thrombin decreased ACC number in the region of the muscle with the largest collateral, and increased the maximum ACC diameter. Another factor that could affect ACC formation is a pre-existing collateral (PEC), which only some Balb/C mice have, so we also separated mice into PEC and non-PEC groups for analysis. In mice with a PEC, thrombin increased ACC number, and both myogenic cells and thrombin increased ACC diameter. There was a trend toward smaller arterialized capillaries in mice with a PEC, which could be because the majority of the blood flow is redirected through the PEC, so the PEC was the main vessel to remodel. These results are consistent with previous studies that indicated that thrombin augments arteriogenesis as well as increasing V-CAM, and suggest that myogenic cells have a similar effect possibly by secreting arteriogenic factors such as VEGF and MMPs. Because myogenic cells increase arteriogenesis, and macrophages are an essential regulator of arteriogenesis, we also tested the hypothesis that myogenic cells would increase macrophage content. Macrophage number increased with ligation, but there was no difference in macrophage number between any of the treatment groups. The lack of difference in macrophage number could be because the day 7 timepoint was too late, as macrophage content peaks at day 3. Because myoblasts increased arteriogenesis, they also may have increased the number M2 macrophages, which are the main macrophage contributor to arteriogenesis, but we used a general macrophage marker and could not detect an increase in M2 macrophages. In future studies, to determine if there is an increase in M2 macrophages a stain specific to M2 macrophages like CD206 could be added. Additionally, a diabetic Balb/C strain could be used to determine if arteriogenesis is impaired in males compared to females in a diseased model.

Rapidly progressive diffuse systemic sclerosis (dSSc) is a life-threatening condition characterized by increased mortality with few effective therapies, typically only helpful in stabilizing disease. Autologous hematopoietic stem cell transplantation (AHSCT) is the only treatment that has demonstrated improved survival. Despite promising results from three randomized controlled trials (RCTs), best practice use of AHSCT in the real-world setting is not well established. The primary objective of this thesis was to summarize the clinical efficacy, limitations and utilization of AHSCT in the management of rapidly progressive dSSc. Specifically, we conducted (1) a systematic review to describe the efficacy of AHSCT in dSSc as well as practice variation in patient selection and treatment regimens; and (2) a multicenter retrospective cohort study to compare outcomes for subjects who received AHSCT in France compared to those who received conventional care in Canada. There was important variability in the criteria for patient selection and treatment protocols. While AHSCT is associated with improved overall survival, skin fibrosis and lung function, further studies are needed to understand its potential for expanded eligibility and effects on other disease manifestations.

Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM.

by Li Chi-kong. / "September 2002." / Thesis (M.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 223-251). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.