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Coming theses from other universities

  • The Importance of Macrophages, Lipid Membranes and Seeding in Experimental AA Amyloidosis Author: Aida Vahdat Shariatpanahi Link: Publication date: 2019-08-15 11:13

    Amyloidosis is a group of protein misfolding diseases caused by tissue deposition of fibrillary protein aggregates termed amyloid. Amyloid A (AA) amyloidosis is a systemic form of amyloidosis that occurs as a complication of chronic inflammatory diseases, such as rheumatoid arthritis, familial Mediterranean fever and chronic infections, such as tuberculosis. AA amyloid is derived from the precursor protein serum amyloid A and is deposited in several organs preferably kidneys, liver and spleen. AA amyloidosis can be induced in mice by long standing inflammatory stimulation and concurrent administration of tissue extracts of AA amyloid, referred to as amyloid enhancing factor (AEF), reduces the time for amyloid deposition in the marginal zone of the spleen from 5 weeks to 2 days. The general aim of this thesis was to investigate the mechanisms involved in the development of AA amyloid in the mouse model of AA amyloidosis.

    Amyloid was induced in inflamed mice by injection of AEF and amyloid toxicity to splenic macrophages was investigated. We found that the marginal zone macrophages were very sensitive to amyloid formation and increasing amyloid load caused progressive depletion of these cells, whereas red pulp macrophages and metallophilic marginal zone macrophages appeared unaffected. To clarify the role of splenic macrophages in amyloidogenesis, macrophages were depleted by clodronate containing liposomes. We displayed that in the absence of splenic macrophages, especially marginal zone macrophages, amyloid formation was delayed implying a crucial role of macrophages in amyloid formation.

    The effect of lipid membranes on amyloid formation was studied and we showed that liposomes exhibited an amyloidogenic effect in inflamed mice although not as powerful as AEF. Following the fate of the liposomes, we showed that liposomes were rapidly cleared by uptake in the spleen and liver and colocalized with lysosomes. A tentative mechanism might be that accumulation of liposomes in lysosomes interfere with the SAA degradation process facilitating amyloid formation.

    Finally the conformational properties of two AEF (AEF1 and AEF2) preparations were studied using conformation sensitive luminescent-conjugated oligothiophenes (LCOs). We found that AEF1 and AEF2 displayed significantly different ultrastructure as well as conformation and consequently induced different cytotoxicity in vitro. Inducing amyloid formation in inflamed mice by AEF1 and AEF2 revealed that the polymorph of the amyloid aggregates was replicated in vivo.

    In summary, the results obtained in this thesis indicate an important role for macrophages for the formation of amyloid. The existence of amyloid strains has long been an in vitro finding, but the finding that AEF ultrastructure drives the morphology of newly formed amyloid in vivo opens up for new studies that can help us to understand the formation of homologous and heterologous fibrils. Thus, the fundamental mechanisms of various amyloid diseases are similar and the results presented in the thesis can increase the understanding of other amyloid diseases.

  • Vascular access incancer patients – clinical implications Author: Knut Taxbro Link: Publication date: 2019-07-23 16:03

    Central venous catheters (CVC) are vital for patients receiving chemotherapy not compatible with peripheral infusion. Thousands of centrally and peripherally inserted central venous catheters are inserted into patients with cancer each year. All types of intravascular catheters are associated with complications. These complications may be divided into infectious, thrombotic, mechanical and occlusive events. All of these events have the potential to harm patients and cause additional expense for the health-care system. Furthermore, the above-mentioned complications are largely avoidable through proper patient selection, insertion technique, hygiene precautions and catheter maintenance.

    Catheter-related infections and deep venous thrombosis are the two most common and feared CVC related complications. Infection in a catheter can cause lifethreatening bacteraemia, and thrombosis can lead to pulmonary embolisation, post-thrombotic syndrome and stenosis of the vessel affected. Many studies describing methods to minimise infectious complications associated with central venous catheters have been carried out. These methods appear to have been implemented in most modern advanced healthcare facilities resulting in a continual decrease in catheter-related infections over the last two decades. New implantation techniques, fewer infections and better catheter materials are likely to have contributed to the reduction in the incidence of catheter-related deep venous thrombosis (CR-DVT). Peripherally inserted central venous catheters (PICC) and subcutaneously implanted vascular access ports (PORT) are two very commonly used catheter devices for delivery of chemotherapy. International guidelines are unclear as to which device to choose due to the paucity of controlled trials.

    The aim of this thesis was to study complications related to central venous access devices used over long periods of time, usually for the delivery of chemotherapy. Vascular access in cancer patients – clinical implications We prospectively studied PORT complications (Study 1) over a six-month follow- up period. In Study 2, we assessed the number of common CVC-related micro- organisms that are transferred across PORT membrane contaminated by a controlled suspension of micro-organisms when a non-coring access needle is inserted using two different techniques. In the largest randomised controlled trial published on this topic (Study 3), we compared PICC with PORT regarding CRDVT and other catheter-related complications. The economic implications of using PICC or PORT were assessed from health-care system´s perspective (Study 4), using data on adverse events and clinical factors (implantation, treatments and dwell-time) from Study 3.

    Chemotherapy against various forms of cancer is very common. Implantation of PORT is one of the ten most common surgical procedures in Sweden according to the Swedish Perioperative Register. Hence, the topic in this thesis may be clinically relevant to many patients and their health care providers.

    We found that the incidence of catheter-related blood stream infection was very low in the cohorts studied. In general, PICCs are associated with significantly more CR-DVTs and adverse events than PORTs. The cost to the health-care system when using PICC is higher than for PORT when complications are included. Given the choice, patients about to commence chemotherapy appear to prefer PORT to PICC. PORT implantation is more painful than PICC insertion, but PICC appears to influence activities of daily life more than PORT.

  • Pain management in older persons with hip fractures Author: Pär Wennberg Link: Publication date: 2019-07-22 09:56