Outcome after allogeneic stem cell transplantation with special reference to non-malignant disorders, chimerism and graft cell composition

The outcome for patients undergoing allogeneic stem cell transplantation (HSCT), a treatment for several severe malignant and non-malignant disorders with hematopoietic origin, is a balancing act between beneficiary effects and risk factors. Treatment success is still limited by excessive immune response, such as graft-versus-host–disease (GVHD) and graft failure (GF), or the lack thereof as in malignancy relapse or severe infections. The main focus of this thesis is to evaluate treatment outcome of different patient groups and evaluate the effect of routine testing for these patients. In 2004, the decision to use an unrelated donor (URD) rather than a HLA-identical sibling for patients with a non-malignant disorder was, due to a higher risk for complications, more debatable than today. In Paper 1, we retrospectively analysed the outcome for 25 patients with non-malignant disorders who underwent HSCT with a unrelated HLA-A,B DRβ1- matched donor. All patients received anti-thymocyte globulin (ATG). Only 2 patients rejected their graft and the cumulative incidence of acute (only grade I and II were diagnosed) and chronic GVHD was 24%, and 21%, respectively. Also, the overall survival (OS) was 84% indicating that the results were comparable to patients undergoing a HSCT with a HLAidentical donor. Chimerism is a PCR-based technique used to determine the genotypic cell origin of post transplantation hematopoiesis for the detection of graft failure (GF) and relapse. Post HSCT, we can find either a mix of donor and recipient, i.e. mixed chimerism (MC) or only cells of donor origin i.e. donor chimerism (DC). In Paper 2, we retrospectively evaluated 58 patients (64 transplants) with non-malignant disorders and studied the outcome in relation to chimerism status and, in addition, how high MC was clinically managed (to avoid GF). We found MC in 64% of the transplants. Donor chimeric (DC) was more common after myeloablative conditioning (MAC) than after reduced conditioning (p=0.04), and patients with DC had a higher incidence of acute GVHD grade II–III (p=0.002) compared to patients with MC. Owing to high MC, no conclusive treatment was established, but patients with GF who underwent a re-HSCT did well. Outcome for adult patients after HSCT have improved. In Paper 3, we compared outcome after HSCT for pediatric patients between time periods 1992-2002 (P1) and 2003 to 2013 (P2). The most significant changes during P2 compared with P1 were a decrease in MAC protocols, altered GVHD prophylaxis and more eligible patients had a non-malignant diagnoses (p=0.002). Results showed more acute GVHD, less transplanted mortality (TRM) but relapse rate was unchanged. In all, 3-year overall survival (OS) improved from 58% in P1 to 78% in P2 (p<0.001). Lastly, pursuing the quest for relevant factors influencing patient outcome, its known that donor grafts entail not only stem cells (CD34+) but also potentially active lymphocytes whos numbers can differ depending on the donor and donor site. In Paper 4, we hypothesized that these donor graft lymphocyte sub-sets could influence patient outcome. We collected and evaluated routine flow cytometry donor graft data (i.e. CD34+, CD3+, CD19+, CD4+, CD8+, CD3-CD56+CD16+, CD4+CD127lowCD25high) for 299 patients with malignant diseases who underwent HSCT between 2006 and 2013 with peripheral blood stem cell grafts (we analysed unrelated separated from sibling donors). The multivariate analysis showed in the unrelated-group an association between a high CD8+ graft dose and decreased risk for relapse (p=0.006) and in the sibling group a high CD19+ graft dose was associated with increased risk for transplanted related mortality (p=0.036) and acute GVHD (p=0.003)

Encounters with patients from Somalia: experience among vocational trainees in Swedish general practice

This study describes how vocational trainees in general medical practice in Sweden experienced encounters with refugee patients from Somalia.Daraasaadkani wuxuu ka hadlayaa waaya-aragnimadii ay ka kasbadeen tababarayaal takhtareed ee Sweden oo ay daaweynaayeen dad qaxooti ah oo ka yimid Soomaaliya.Questo studio descrive l'esperienza dei tirocinanti in medicina generale in Svezia con pazienti rifugiati provenienti dalla Somalia

Luojan kiitos, että olen lesbo : homoseksuaalisuudesta

Aineisto on Opiskelijakirjaston digitoimaa ja Opiskelijakirjasto vastaa aineiston käyttöluvist

Hvilke variabler er avgjørende for lederens evne til å håndtere drastiske endringer?

Fra et evolusjonsperspektiv bærer næringslivet mange likheter med Galapagos øyene. På disse øyene eksisterer det et rikt antall dyrearter som er godt tilpasset sine mikrosystemer. De forskjellige dyreartene er så godt tilpasset de ulike omgivelser at de har overlevd her i tusenvis av år. Evolusjon har gjort dem så godt integrert at de har blitt nærmest perfekte for å overleve sett i forhold til hvor de befinner seg. Den berømte hvithaien er øyenes største rovdyr. Den kan oppnå hastigheter på 40 km/h, ser i mørket, og gror sine 300 tenner tilbake nærmest på dagen. Rundt disse øyene er den det perfekte rovdyr. Men hva om vi drastisk endrer disse omgivelsene? Dersom vi flytter hvithaibestanden opp på land vil det perfekte rovdyret avgi et siste sprelleshow, før arten raskt blir utryddet. Så hvordan henger dette sammen med næringslivet? Næringslivet består også av et rikt antall individer som er nærmest perfekt tilpasset sine mikrosystemer. Kortsiktig er disse individene ledene innen sine respektive bransjer, men hva skjer når disse bransjene nærmest over natten endrer seg? Kodak, Nokia, Sears er alle eksempler på bedrifter som ikke klarte å tilpasse seg til de nye reglene, som hvithaien på land. Næringslivet endrer seg mye raskere en øyene på Galapagos. Historien er heldigvis beriket med individer som klarer å adaptere til de disse endringene gang på gang. Dette studiet vil derfor dedikeres til å finne “hvilke variabler som er avgjørende for en leders evne til å håndtere drastiske endringer

Long-Range Chromosomal Mapping of the Carcinoembryonic Antigen (CEA) Gene Family Cluster

A long-range physical map of the carcinoembryonic antigen (CEA) gene family cluster, which is located on the long arm of chromosome 19, has been constructed. This was achieved by hybridization analysis of large DNA fragments separated by pulse-field gel electrophoresis and of DNA from human/rodent somatic cell hybrids, as well as the assembly of ordered sets of cosmids for this gene region into contigs. The different approaches yielded very similar results and indicate that the entire gene family is contained within a region located at position 19q13.1–q13.2 between the CYP2A and the D19S15/D19S8 markers. The physical linkage of nine genes belonging to the CEA subgroup and their location with respect to the pregnancy-specific glycoprotein (PSG) subgroup genes have been determined, and the latter are located closer to the telomere. From large groups of ordered cosmid clones, the identity of all known CEA subgroup genes has been confirmed either by hybridization using gene-specific probes or by DNA sequencing. These studies have identified a new member of the CEA subgroup (CGM8), which probably represents a pseudogene due to the existence of two stop codons, one in the leader and one in the N-terminal domain exons. The gene order and orientation, which were determined by hybridization with probes from the 5′ and 3′ regions of the genes, are as follows: cen/3′-CGM7-5′/3′-CGM2-5′/5′-CEA-3′/5′-NCA-3′/5′- CGM1-3′/3′-BGP-5′/3′-CGM9-5′/3′-CGM6-5′/5′-CGM8-3′/PSGcluster/qter

Carcinoembryonic Antigen Gene Family

The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin supergene family and can be divided into two main subgroups based on sequence comparisons. In humans it is clustered on the long arm of chromosome 19 and consists of approximately 20 genes. The CEA subgroup genes code for CEA and its classical crossreacting antigens, which are mainly membrane-bound, whereas the other subgroup genes encode the pregnancy-specific glycoproteins (PSG), which are secreted. Splice variants of individual genes and differential post-translational modifications of the resulting proteins, e.g., by glycosylation, indicate a high complexity in the number of putative CEA-related molecules. So far, only a limited number of CEA-related antigens in humans have been unequivocally assigned to a specific gene. Rodent CEA-related genes reveal a high sequence divergence and, in part, a completely different domain organization than the human CEA gene family, making it difficult to determine individual gene counterparts. However, rodent CEA-related genes can be assigned to human subgroups based on similarity of expression patterns, which is characteristic for the subgroups. Various functions have been determined for members of the CEA subgroup in vitro, including cell adhesion, bacterial binding, an accessory role for collagen binding or ecto-ATPases activity. Based on all that is known so far on its biology, the clinical outlook for the CEA family has been reassessed

Workplace learning from a socio-cultural perspective: creating developmental space during the general practice clerkship

Workplace learning in undergraduate medical education has predominantly been studied from a cognitive perspective, despite its complex contextual characteristics, which influence medical students’ learning experiences in such a way that explanation in terms of knowledge, skills, attitudes and single determinants of instructiveness is unlikely to suffice. There is also a paucity of research which, from a perspective other than the cognitive or descriptive one, investigates student learning in general practice settings, which are often characterised as powerful learning environments. In this study we took a socio-cultural perspective to clarify how students learn during a general practice clerkship and to construct a conceptual framework that captures this type of learning. Our analysis of group interviews with 44 fifth-year undergraduate medical students about their learning experiences in general practice showed that students needed developmental space to be able to learn and develop their professional identity. This space results from the intertwinement of workplace context, personal and professional interactions and emotions such as feeling respected and self-confident. These forces framed students’ participation in patient consultations, conversations with supervisors about consultations and students’ observation of supervisors, thereby determining the opportunities afforded to students to mind their learning. These findings resonate with other conceptual frameworks and learning theories. In order to refine our interpretation, we recommend that further research from a socio-cultural perspective should also explore other aspects of workplace learning in medical education

Conditions for transformative learning for sustainable development: a theoretical review and approach

Continued unsustainability and surpassed planetary boundaries require not only scientific and technological advances, but deep and enduring social and cultural changes. The purpose of this article is to contribute a theoretical approach to understand conditions and constraints for societal change towards sustainable development. In order to break with unsustainable norms, habits, practices, and structures, there is a need for learning for transformation, not only adaption. Based on a critical literature review within the field of learning for sustainable development, our approach is a development of the concept of transformative learning, by integrating three additional dimensions—Institutional Structures, Social Practices, and Conflict Perspectives. This approach acknowledges conflicts on macro, meso, and micro levels, as well as structural and cultural constraints. It contends that transformative learning is processual, interactional, long-term, and cumbersome. It takes place within existing institutions and social practices, while also transcending them. The article adopts an interdisciplinary social science perspective that acknowledges the importance of transformative learning in order for communities, organizations, and individuals to be able to deal with global sustainability problems, acknowledging the societal and personal conflicts involved in such transformation