Purpose: To describe the experience of managing relapsing-remitting multiple sclerosis among adult women users of injectable disease modifying drugs, including day-to-day management, medication beliefs, and health care provider influence. Rationale/Significance of the study:Approximately 85% of the 400,000 Americans with multiple sclerosis have relapsing-remitting multiple sclerosis (RRMS), characterized by unpredictable relapses and partial or full remissions of neurological symptoms. Untreated, RRMS may progress to permanent, irreversible disability and decreased quality of life. Current guidelines recommend immediate and sustained treatment with injectable disease modifying drugs (DMDs). However, despite pronounced modest benefits, approximately 30%-62% of patients are not undergoing DMD therapy. A small number of quantitative studies have identified factors that predict adherence to injectable DMDs. However, little is known about injectable DMDs from patients’ perspectives. It is important to develop an understanding of the experience of managing RRMS among adult users of injectable DMDs in order for health care providers to provide ongoing education, counseling, and support. Organizing Framework:The framework, Beliefs About Medicines, was used to guide the study. Design: Qualitative descriptive design. Setting: Data were collected from adult women with RRMS who received care from an MS clinic, a neurology practice, and through snowball sampling. Sample: Purposive and theoretical sampling was used to recruit 32 women with RRMS. Maximum variation sampling ensured the appropriate breadth and depth of experiences. Women currently undergoing injectable DMD therapy (n = 25), as well as women who either discontinued (n = 6), or never used (n = 1) injectable DMDs were interviewed. Methods: A qualitative descriptive design was utilized. Verification occurred through trustworthiness of data, including rich, thick description from qualitative interviews; field notes and memoing; and member checks. Simultaneous data collection, analysis, and interpretation facilitated interview revision in order to elicit or expand emerging themes. Content analysis inductively derived themes and patterns within and across categories. Participant quotes substantiated particular themes. Confirmability of the data analysis process was undertaken in consultation with the research advisor. Implications: Findings elucidated adult women’s subjective experiences concerning management of RRMS among users of DMDs, including day-to-day management, medication beliefs, and health care provider influence. Results from this study can be used to educate, counsel, and support women in the management of RRMS.

No description available.

Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. The etiology of MS is unknown but many researchers believe that it is autoimmune mediated. This study investigated naive CD4+ and naive CD8+ T-cell homeostasis in patients with Primary Progressive Multiple Sclerosis and Relapsing Remitting Multiple Sclerosis. The naive T-cell compartment involves a balance between thymic production of naive T-cells, homeostatic proliferation and the delivery of death and survival signals. Naive T-cell production was quantified by measuring signal joint T-cell receptor excision circles (sj-TRECs); episomal byproducts formed during V(D)J T-cell receptor rearrangement. / Homeostatic proliferation was quantified by flow cytometry analysis of % expression of CD31 and Ki-67. CD31 is a marker found on CD4+ recent thymic emigrants (RTE) but not on naive T-cells that have undergone homeostatic proliferation. CD31 can be used as a marker of the proliferation history of naive CD4+ T-cells. Ki-67 is a nuclear and nucleolar antigen found in actively cycling cells. It can be used as a marker of cell proliferation at the moment of isolation. Cell survival was measured by quantifying plasma IL-7 levels and by measuring Bcl-2 expressions. IL-7 plays an important role in maintaining and restoring peripheral naive T-cell homeostasis. It stimulates naive T-cell proliferation and prevents the reduction of Bcl-2, an antiapoptotic protein. / In this study, PPMS patients had significantly reduced naive CD4 + T-cell sj-TRECs compared to healthy controls (p = 0.0007) and compared to RRMS patients (p = 0.0010). RRMS patients had fewer sj-TRECs than healthy controls but this difference was not significant (p = 0.4652). Similarly, in PPMS, naive CD4+ T-cells had significantly lower CD31 expression than healthy controls (p = 0.0017) and RRMS patients (p = 0.0032). This finding indicates increased homeostatic proliferation in naive CD4 + T-cells in PPMS, most probably a response to decreased thymic export as marked by the decreased naive CD4+ T-cell sj-TRECs. % CD31 expression in naive CD4+ T-cells did not differ significantly in RRMS compared to healthy controls (p = 0.7455) which is consistent with their naive CD4+ sj-TREC levels. / Naive CD8+ T-cell sj-TRECs were significantly reduced in PPMS patients compared to healthy controls (p = 0.0212) but not compared to RRMS patients (p = 0.2379). RRMS patients had fewer naive CD8 + T-cell sj-TRECs compared to healthy controls but this difference was not significant (p = 0.1517). PPMS patients expressed increased Bcl-2 levels in their naive CD8+ T-cells. This finding indicates upregulation of survival signals, most probably a consequence of reduced thymic export of naive CD8+ T-cells. / The data from this study indicate that PPMS is different from RRMS in their naive CD4+ T-cell sj-TRECs and naive CD4 + T-cell % CD31 expression but is similar to RRMS in their naive CD8+ T-cell sj-TRECs. This study concludes, therefore, that both PPMS and RRMS patients have altered naive T-cell homeostasis.

No description available.

Diss. (sammanfattning) Umeå : Umeå universitet, 2010. / Härtill 5 uppsatser.

Background: Managing medication during pregnancy and lactation in multiple sclerosis (MS) patients needs to balance potential risks to the newborn with the substantial risks of ongoing disease activity. Objective: To evaluate the potential transfer of natalizumab (NAT) into breast milk and into the serum of newborn babies in women who continued NAT treatment during pregnancy and lactation. Methods: Serum samples of 11 mother–infant pairs and mother milk samples of a further 4 women were analyzed for free NAT using a HL60 cell-based fluorescence-activated cell sorting (FACS) assay. Two mother–baby pairs were analyzed for cell-bound NAT, very-late-antigen (VLA)-4 expression, and saturation with NAT on immune cells by FACS analysis. Results: In the majority of the mother–infant serum pairs (6/11) and in all breast milk samples, free NAT was detectable. Cell-bound NAT was measurable in both mother–baby pairs with significant higher levels in babies. VLA-4 expression seems to be higher in newborns. Saturation with NAT was comparable between newborns and mothers. Conclusion: NAT can pass placental barrier before delivery and into breast milk. Measurable NAT on neonatal lymphocytes may have functional impact. Further investigations are needed to clarify safety and risk of NAT exposure during pregnancy and lactation.

Indiana University-Purdue University Indianapolis (IUPUI) / Lyme disease, the most prevalent vector-borne illness in the United States, is a multisystem inflammatory disorder caused by infection with the spirochete Borrelia burgdorferi (Bb). This spirochete is maintained in nature through an enzootic cycle involving ticks and small mammals. The Bb genome encodes a large number of surface lipoproteins, many of which are expressed during mammalian infection. One of these lipoproteins is the major outer surface protein C (OspC) whose production is induced during transmission as spirochetes transition from ticks to mammals. OspC is required for Bb to establish infection in mice and has been proposed to facilitate evasion of innate immunity. However, the exact biological function of OspC remains elusive. Our studies show the ospC-deficient spirochete could not establish infection in NOD-scid IL2rγnull mice that lack B cells, T cells, NK cells, and lytic complement, whereas the wild-type spirochete was fully infectious in these mice. The ospC mutant also could not establish infection in SCID and C3H mice that were transiently neutropenic during the first 48 h post-challenge. However, depletion of F4/80+ phagocytes at the skin-site of inoculation in SCID mice allowed the ospC mutant to establish infection in vivo. In phagocyte-depleted SCID mice, the ospC mutant was capable to colonize the joints and triggered neutrophilia during dissemination in a similar pattern as wild-type bacteria. We then constructed GFP-expressing Bb strains to evaluate the interaction of the ospC mutant with phagocytes. Using flow cytometry and fluorometric assay for phagocytosis, we found that phagocytosis of GFP-expressing ospC mutant spirochetes by murine peritoneal macrophages and human THP-1 cells was significantly higher than parental wild-type Bb strains, suggesting that OspC has an anti-phagocytic property. This enhancement in phagocytosis was not mediated by MARCO and CD36 scavenger receptors and was not associated with changes in mRNA levels of TNFα, IL-1β, and IL-10. Phagocytosis assays with HL60 neutrophil-like cells showed that uptake of Bb strains was independent to OspC. Together, our findings reveal that F4/80+ phagocytes are important for clearance of the ospC mutant, and suggest that OspC promotes spirochetes' evasion of macrophages in the skin of mice during early Lyme borreliosis.

No description available.

No description available.

<p></p> <p><strong><em>Background </em></strong></p> <p>Oral pharmacotherapy has the potential to offer multiple sclerosis patients improved clinical outcomes compared to traditional therapies.</p> <p><strong><em>Objectives </em></strong></p> <p>This review assesses the effects of oral therapies compared to placebo and interferon beta-1a in adults with relapsing-remitting multiple sclerosis (RRMS).</p> <p><strong><em> </em></strong></p> <p><strong><em>Search methods </em></strong></p> <p>We searched the MEDLINE, EMBASE, Cochrane Library, Web of Science (January 1980 to April 2011) and clinincaltrials.gov (April 2011) databases and reference lists of articles. The FDA website was also searched.</p> <p><strong><em>Selection criteria </em></strong></p> <p>Double-blind, placebo-controlled, randomized trials of RRMS patients who were treated with fingolimod, cladribine, laquinimod or interferon beta-1a.</p> <p><strong><em>Data collection and analysis </em></strong></p> <p>Two reviewers independently assessed articles for inclusion. Data extraction and quality assessment was completed by one reviewer and verified for accuracy. Meta-analysis and indirect treatment comparison methods were used to estimate relative measures of efficacy.</p> <p><strong><em>Results </em></strong></p> <p>Although 11 trials involving 7,127 participants were included in this review, only 2,109 (30%) and 1,738 (24%) participants contributed to the direct and indirect estimates respectively, for the primary outcome, annualized relapse rate. Oral therapy and interferon beta-1a had a significantly different rate of relapse compared to placebo (Mean difference [MD] -0.21, 95% confidence interval [CI] -0.27 to -0.16 , p < 0.00001 and MD -0.33 95% CI -0.65 to -0.01). There was a significant risk reduction of 37% and 19% in the number of patients with at least one relapse for oral therapy and interferon beta-1a compared to placebo respectively. Safety analysis favoured placebo for both sets of trials (p=0.002 and p=0.04). Indirect estimates were not significant for all three outcomes however; comparability between direct evidence was noted.</p> <p><strong><em>Conclusions </em></strong></p> <p>Oral pharmacotherapy and interferon beta-1a are effective compared to placebo in controlling relapse rate in patients with RRMS. The indirect measures of effect provide initial estimates of comparative efficacy and incorporation of future evidence will be necessary.</p> / Master of Science (MSc)