The aim of this thesis was to investigate oral cryotherapy (OC) as prophy-laxis against oral mucositis (OM) in patients given high-dose chemotherapy for stem cell transplantation (SCT). A new mouth rinse device was tested for possible additive effect to OC. For study I-III, 78 patients were randomised to OC or standard oral care (SOC). Papers I and II showed that OC patients had significantly less severe mucositis, pain, opioid use, lower C-reactive protein and less parenteral nutrition treatment (TPN). There was no difference in relapse rate, and 5-year survival was unexpectedly significantly better in the OC group (Paper III). In paper IV, the local effect of OC on the mucosa of the mouth was investigated by the use of an infrared thermograph. Change in surface temperature in eight areas of the mouth cavity was measured after cooling of the mouth in healthy volunteers. A substantial lowering of the temperature (-12.9 °C, mean) was seen which could explain the efficacy of OC. To exclude that acute cooling in itself is traumatic, the proinflammatory cytokine IL-6 was measured in saliva and showed no increase after cooling. Paper V reported a study in 40 allogeneic SCT patients. 20 were given SOC including OC and 20 in addition received Caphosol®, a calcium phosphate mouth rinse, during chemotherapy and until day 21. Severity of mucositis, use of opioids and TPN, effects on nutrition and CRP levels were measured. No significant difference was found between the groups in any of these variables, but a non-significant trend for an advantage for the combination could be seen. IL-6 saliva levels were measured. There was a substantial increase (more than 10-fold), in mean IL-6 levels from baseline to beginning of mucositis and a weak correlation between increased IL-6 levels and severity of OM, suggesting that IL-6 in saliva may be a useful marker of the inflammatory mucosal process. This thesis demonstrates that OC is effective as prophylaxis against chemotherapy-induced OM. As a consequence of this work, OC has been introduced as the standard of care in all SCT patients in our institution.

Wound healing is governed by a complex cascade of related processes, involving cells, extracellular matrix and cytokines. In adults this always results in a scar whilst embryonic wound healing is scarless and extensive research worldwide is aimed at reducing scarring in adults. A mathematical framework for problems in dermal wound healing is developed that incorporates models of the individual processes involved. Cells are modelled as discrete individuals. Cytokines and other biologically active factors are modelled as continua. A novel tensorial approach is taken to modelling the extracellular matrix. The numeric and computational challenges associated with combining models for the individual processes are identified and investigated. These include the development of data structures and numeric methods for the continuous and discrete species. Effective visualisation methods for the large amounts of data generated by the model are also discussed. The possibilities offered by high performance computing in mathematical biology are highlighted in this work. The final part of this thesis gives an example of a combined model of the inflammatory and proliferative phases of dermal wound healing using the new computational framework. Both quantitative and qualitative methods are used to analyse the information-rich data sets generated by the model, offering insight into the dynamic systems that can be modelled using the new approach.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Heidelberg, Univ., Diss., 2006.

Heidelberg, Univ., Diss., 2008.

Hohenheim, Univ., Diss., 2008.

Tübingen, Univ., Diss., 2006.

Thesis (Ph. D.)--University of Oklahoma. / Bibliography: leaves 143-161.