The aim of this thesis was to develop and evaluate a new way of monitoring blood flow with microdialysis. A thin catheter consisting of a semipermeable membrane is implanted in the tissue being studied. The catheter is perfused by a solution that closely resembles interstitial fluid, and small water-soluble substances are allowed to diffuse passively through the pores of the membrane with the aim at reaching equilibrium with the surrounding tissue.  The minimally invasive character of microdialysis, and its ability to sample from the organ being studied, make microdialysis attractive in most research settings as well as for clinical surveillance. It has, however, become increasingly evident that microdialysis under conditions of non-equilibrium - for example, fluctuating regional blood flow, will alter the results gained. We have therefore aimed to explore the possibilities of developing a new marker of blood flow that will yield information about changes in blood flow that occur in the area of the microdialysis catheter itself. We hypothesised that the changes in the diffusion of exogenous urea could be used as markers of changes in tissue blood flow. The theoretical basis for this approach is that the mass transfer of urea will increase across the dialysis membrane secondary to increased blood flow. As removal of urea from the vicinity of the dialysis membrane increases with increased blood flow, the concentration gradient of urea between the perfusate and tissue will also increase. This in turn will result in a greater loss of urea from the perfusate. The changes noted in retrieval of urea from dialysate by the system are therefore thought to be inversely related to changes in blood flow. We tested our hypothesis in two species of animal (rat and pig) and in man, and in three organ systems (muscle, liver, and skin), and present four papers that indicate that the urea clearance technique provides reliable and reproducible results. The technique was evaluated against conventional metabolic markers (lactate and glucose), the ethanol clearance technique (microdialysis), laser Doppler perfusion imaging (LDPI), and polarisation light spectroscopy (TiVi). We present evidence that the urea clearance technique can be used to assess blood flow in the organs studied reliably and reproducibly with microdialysis. The microdialysis technique is minimally invasive and safe for the recipient, and catheters can easily be implanted during operation to monitor organs at risk. Urea is easily analysed as a standard assay among other “basic” metabolic markers (in a standard microdialysis kit) and has favourable characteristics with a standardised measurement system that is routinely used for monitoring metabolites in the clinic. The technique is also effective when used at lower perfusate flow rates (<1 μl/minute), which is advantageous as the recovery of metabolic markers increases at low perfusate flow rates.

<p>Full thickness wounds, such as deep burns, need restoration of both the dermal and epidermal layers of the skin. In normal wound healing, re-epithelialization occurs by migration and proliferation of keratinocytes from the wound edges and by differentiation of stem cells from remaining hair follicles. Restoration of dermis occurs by influx of growth factors secreted by macrophages, platelets, and fibroblasts; by fibroblast proliferation and subsequent synthesis and remodeling of collagenous dermal matrix. In the case of full-thickness acute burn injuries and chronic wounds (e.g. pressure ulcers, venous ulcers and diabetic foot ulcers), these processes are defective. With the principles of tissue engineering in mind (to correct, improve and maintain tissues and their functions), researchers have developed promising materials and methods to make it possible to restore either the dermal (Integra^® DRT, Alloderm^®) or the epidermal layer (split thickness skin grafts (STSG), cultured epithelial autografts (CEA), autologous keratinocytes in single cell suspension). It is now well established that superior results are obtained if both dermal and epidermal components are combined, for example in a bilayered skin equivalent.<strong> </strong>Apligraf^®is recommended for use on venous ulcers and is the only bilayered living skin equivalent currently approved by the FDA. Studies on different factors affecting the wound healing capacity as well as techniques in use provide valuable information for further development.</p><p>In this licentiate thesis, we evaluated different transplantation techniques for delivering cultured human keratinocytes in single cell suspension, a measure becoming more frequently used in addition to STSG and CEA for restoring the epidermal layer of the skin. We found that the pressure device, commonly used to spray cell suspension onto the wound with pressures as high as 200 kPa, killed around 0% of the cells. In comparison, an ordinary syringe with the attachment of a spray nozzle showed almost 90% viable cells post transplantation and provided an equally good distribution of the cell suspension.</p><p>We also studied different silver containing dressings regarding silver accumulation in human skin. In addition, we graded the re-epithelialization to evaluate whether the dressings caused any delay in the wound healing process. We found that the silver dressings tested, with few exceptions, caused dermal accumulation of silver, primarily aggregated around blood vessels. We could also show that most of the dressings had negative effect on the re-epithelialization.</p><p>For the restoration of the dermal layer of the skin, Integra^® DRT functions as a scaffold for guided tissue regeneration of the dermis. We had the possibility to study a case of necrotizing fasciitis were the treatment consisted of the use of Integra^® DTR together with sub-atmospheric pressure (after initial surgical debridement) and later transplantation of split thickness skin grafts. This measure proved to be safe as well as giving satisfactory pliable and aesthetically acceptable result.</p>

<p>Följande studie är en undersökning av vilka faktorer som påverkar kundernas upplevda kvalitet vid ett privat företag inom plastikkirurgibranschen. Studien syftar till att undersöka vilka kvalitetsfaktorer som kunderna upplever, vilka faktorer som är viktigast samt hur de olika faktorerna relaterar till varandra. Därutöver undersöks om kundernas syn skiljer sig åt före och efter ett ingrepp. Studien har genomförts i intervjuform med en huvudsakligen induktiv metod, och tar sitt teoretiska avstamp i såväl företagsekonomisk tjänstemarknadsföringsteori som forskning från sjukvårdsområdet. Den bild som framträtt överrensstämmer i stort med den traditionella tjänstemarknadsföringssynen, med undantag för att resultatfaktorer visat sig vara klart viktigare än processfaktorer. Dessutom har en kvalitetsfaktor, trygghet, som i tidigare forskning inte funnits vara användbar identifierats som potentiellt mycket viktig.</p>

Följande studie är en undersökning av vilka faktorer som påverkar kundernas upplevda kvalitet vid ett privat företag inom plastikkirurgibranschen. Studien syftar till att undersöka vilka kvalitetsfaktorer som kunderna upplever, vilka faktorer som är viktigast samt hur de olika faktorerna relaterar till varandra. Därutöver undersöks om kundernas syn skiljer sig åt före och efter ett ingrepp. Studien har genomförts i intervjuform med en huvudsakligen induktiv metod, och tar sitt teoretiska avstamp i såväl företagsekonomisk tjänstemarknadsföringsteori som forskning från sjukvårdsområdet. Den bild som framträtt överrensstämmer i stort med den traditionella tjänstemarknadsföringssynen, med undantag för att resultatfaktorer visat sig vara klart viktigare än processfaktorer. Dessutom har en kvalitetsfaktor, trygghet, som i tidigare forskning inte funnits vara användbar identifierats som potentiellt mycket viktig.

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To correct, improve, and maintain tissues, and their functions, are common denominators in tissue engineering and reconstructive plastic surgery. This can be achieved by using autolo-gous tissues as in flaps or transplants. However, often autologous tissue is not useable. This is one of the reasons for the increasing interest among plastic surgeons for tissue engineering, and it has led to fruitful cross-fertilizations between the fields. Tissue engineering is defined as an interdisciplinary field that applies the principles of engineering and life sciences for development of biologic substitutes designed to maintain, restore, or improve tissue functions. These methods have already dramatically improved the possibilities to treat a number of medical conditions, and can arbitrarily be divided into two main principles: &gt; Methods where autologous cells are cultured in vitro and transplanted by means of a cell suspension, a graft, or in a 3-D biodegradable matrix as carrier. &gt; Methods where the tissue of interest is stimulated and given the right prerequisites to regenerate the tissue in vivo/situ with the assistance of implantation of specially designed materials, or application of substances that regulate cell functions - guided tissue regeneration. We have shown that human mammary epithelial cells and adipocytes could be isolated from tissue biopsies and that the cells kept their proliferative ability. When co-cultured in a 3-D matrix, patterns of ductal structures of epithelial cells embedded in clusters of adipocytes, mimicking the in vivo architecture of human breast tissue, were seen. This indicated that human autologous breast tissue can be regenerated in vitro. The adipose tissue is also generally used to correct soft tissue defects e.g. by autologous fat transplantation. Alas 30-70% of the transplanted fat is commonly resorbed. Preadipocytes are believed to be hardier and also able to replicate, and hence, are probably more useful for fat transplantation. We showed that by using cell culture techniques, significantly more pre-adipocytes could survive and proliferate in vitro compared to two clinically used techniques of fat graft handling. Theoretically, a biopsy of fat could generate enough preadipocytes to seed a biodegradable matrix that is implanted to correct a defect. The cells in the matrix will replicate at a rate that parallels the vascular development, the matrix subsequently degrades and the cell-matrix complex is replaced by regenerated, vascularized adipose tissue. We further evaluated different biodegradable scaffolds usable for tissue engineering of soft tissues. A macroporous gelatin sphere showed several appealing characteristics. A number of primary human ecto- and mesodermal cells were proven to thrive on the gelatin spheres when cultured in spinner flasks. As the spheres are biodegradable, it follows that the cells can be cultured and expanded on the same substrate that functions as a transplantation vehicle and scaffold for tissue engineering of soft tissues. To evaluate the in vivo behavior of cells and gelatin spheres, an animal study was performed where human fibroblasts and preadipocytes were cultured on the spheres and injected intra-dermally. Cell-seeded spheres were compared with injections of empty spheres and cell suspensions. The pre-seeded spheres showed a near complete regeneration of the soft tissues with neoangiogenesis. Some tissue regeneration was seen also in the ‘naked’ spheres but no effect was shown by cell injections. In a human pilot-study, intradermally injected spheres were compared with hyaluronan. Volume-stability was inferior to hyaluronan but a near complete regeneration of the dermis was proven, indicating that the volume-effect is permanent in contrast to hyaluronan which eventually will be resorbed. Further studies are needed to fully evaluate the effect of the macroporous gelatin spheres, with or without cellular pre-seeding, as a matrix for guided tissue regeneration. However, we believe that the prospect to use these spheres as an injectable, 3D, biodegradable matrix will greatly enhance our possibilities to regenerate tissues through guided tissue regeneration. / On the day of the defence date the status of article V was In Press.

Syfte och frågeställningar Syftet med denna studie är att förklara hur subjektiva upplevelser runt familj påverkar intresse av estetisk kirurgi. Specifika frågeställningar har formulerats för att undersöka detta: – Hur påverkas intresse av estetisk kirurgi av familjemedlemmar som pratat om att utföra eller som har utfört estetisk kirurgi? – Hur påverkas intresse av estetisk kirurgi av upplevd skilsmässa under uppväxt och uppväxt med en ensamstående förälder? – Hur påverkas intresse av estetisk kirurgi av fysisk eller psykisk frånvaro av mamma eller pappa under uppväxt? – Hur påverkas intresse av estetisk kirurgi av att minst en person gett stöd och varit älskande under uppväxt? – Hur påverkas intresse av estetisk kirurgi av ouppnådda familjefunktioner? – Hur påverkas intresse av estetisk kirurgi av en upplevd familjekris? Metod Denna uppsats har använts sig av en kvantitativ forskningsmetod med enkät. En egen enkät komponerades och delades ut i Stockholms län. 60 enkäter delades ut, varav 58 av dessa besvarades. Enkäterna hanterades anonymt och sammanställdes först i Excel-ark för att sedan analyseras i SPSS genom Mann-Whitney och Chi-2 test, samt logistisk regression. Resultat Prediktorer för intresse för estetisk kirurgi är föräldrar som pratat om att utföra estetisk kirurgi (P=0,049), lägre skattning av psykisk närvaro av mamma (P=0,029), lägre skattning av psykisk närvaro av pappa (P=0,042), lägre skattning av att pappa ingivit respekt kring den egna personens värde (P=0,001) och vid lägre skattning av att familj gett en god grund för en stabil och harmonisk uppväxt (P=0,003). Ingen av dessa kunde enskilt förklara den beroende variabelns variation, utan alla samvarierade. Genom att stegvis exkludera prediktorer i en logistisk regression kunde den viktigaste prediktorn till intresse av estetisk kirurgi identifieras, vilket var, den sistnämnda. Slutsats Slutsatsen är att vissa subjektiva upplevelser runt familj påverkar intresse av estetisk kirurgi medan påverkan av andra inte gett signifikanta skillnader. / Aim The purpose of this study is to explain how subjective experiences around the family affect interest in esthetic surgery. Specific questions were made to investigate this: - How is the interest in esthetic surgery affected by family members who has been talking about undergoing or have been undergoing esthetic surgery? - How is the interest in esthetic surgery affected by the experience of divorce during childhood and growing up with a single parent? - How is the interest in esthetic surgery affected by physical or psychological absence of mother or father, during childhood? - How is the interest in esthetic surgery affected by at least one person who has been supported and loving, during childhood? - How is the interest in esthetic surgery affected by family functions that are unmet? - How is the interest in esthetic surgery affected by the experience of a family crisis? Method This thesis has used a quantitative research method, with a survey. An own survey was made, and handed out in Stockholm. 60 surveys was handed out, of which 58 was answered. The survey was managed anonymously, and at first consolidated in spreadsheets of Excel and then analyzed in SPSS, trough Mann-Whitney and Chi-2 test, and also logistic regression. Results The predictors of interest in esthetic surgery are parents who talked about undergoing esthetic surgery (P = 0.049), lower estimates of mental presence of the mother (P = 0.029), lower estimates of mental presence of father (P = 0.042), lower estimate of that the father has given respect of the own person´s value (P = 0.001) and lower estimation of that the family have provided a good basis for a stable and harmonious childhood (P = 0.003). None of these could individually explain the dependent variable's variation, but all of them interacted. By gradually exclude the predictors in a logistic regression, the main predictor of interest in esthetic surgery was identified, which was the last one mentioned. Conclusions The conclusion is that certain subjective experiences around the family affect interest in cosmetic surgery, while the influence of others has shown no significant differences.

<p>A severe burn is a trauma fraught with stress and pain and may change the entire course of life. This thesis focuses on care utilisation, care experiences and patient satisfaction after a severe burn.</p><p>The patients studied were treated at the Burn Unit at Uppsala University Hospital between 1980 and 2006. Burn-related health was examined using the Burn Specific Health Scale-Brief (BSHS-B), personality traits with the Swedish universities Scales of Personality (SSP), psychological symptoms using the Hospital Anxiety and Depression scale (HADS), symptoms of posttraumatic stress with the Impact of Event Scale-Revised (IES-R) and satisfaction with care using the Patient Satisfaction-Results and Quality (PS-RESKVA) questionnaire.</p><p>Those utilising care years after injury reported poorer functioning on three of the BSHS-B subscales. Personality traits had a greater impact on care utilisation than injury severity.</p><p>Social desirability was lower among care utilisers and was associated with burn-related health aspects.</p><p>The participants reported a low level of negative care experiences, the most common of which was Powerlessness.</p><p>Most patients were satisfied with care, more with quality of contact with the nursing staff, and less with treatment information. Multiple regressions showed that the BSHS-B Interpersonal relationships subscale was an independent variable related to all measured aspects of patient satisfaction. The highest adjusted R² was 0.25.</p><p>In a prospective assessment with multiple regression analyses, Age and Education, the personality traits of Stress susceptibility, Trait irritability, Detachment and Social desirability, in addition to the post-traumatic stress symptoms Intrusion and Hyperarousal, were predictors of satisfaction with care. The highest adjusted R² was 0.19.</p><p>The thesis has pointed out that interpersonal factors are related to care utilisation as well as satisfaction with care. However, satisfaction with care was only moderately associated with health and individual characteristics, which may imply that the care itself is of major importance.</p>

A severe burn is a trauma fraught with stress and pain and may change the entire course of life. This thesis focuses on care utilisation, care experiences and patient satisfaction after a severe burn. The patients studied were treated at the Burn Unit at Uppsala University Hospital between 1980 and 2006. Burn-related health was examined using the Burn Specific Health Scale-Brief (BSHS-B), personality traits with the Swedish universities Scales of Personality (SSP), psychological symptoms using the Hospital Anxiety and Depression scale (HADS), symptoms of posttraumatic stress with the Impact of Event Scale-Revised (IES-R) and satisfaction with care using the Patient Satisfaction-Results and Quality (PS-RESKVA) questionnaire. Those utilising care years after injury reported poorer functioning on three of the BSHS-B subscales. Personality traits had a greater impact on care utilisation than injury severity. Social desirability was lower among care utilisers and was associated with burn-related health aspects. The participants reported a low level of negative care experiences, the most common of which was Powerlessness. Most patients were satisfied with care, more with quality of contact with the nursing staff, and less with treatment information. Multiple regressions showed that the BSHS-B Interpersonal relationships subscale was an independent variable related to all measured aspects of patient satisfaction. The highest adjusted R2 was 0.25. In a prospective assessment with multiple regression analyses, Age and Education, the personality traits of Stress susceptibility, Trait irritability, Detachment and Social desirability, in addition to the post-traumatic stress symptoms Intrusion and Hyperarousal, were predictors of satisfaction with care. The highest adjusted R2 was 0.19. The thesis has pointed out that interpersonal factors are related to care utilisation as well as satisfaction with care. However, satisfaction with care was only moderately associated with health and individual characteristics, which may imply that the care itself is of major importance.

Tissue engineering applies principles of biology and engineering to the development of functional substitutes for damaged or lost tissues. Tools for the neo-generation of tissue in tissue engineering research include cells, biomaterials and soluble factors. One main obstacle in tissue engineering is the limited availability of autologous tissue specific progenitor cells. This has led to interest into using autologous cells with stem cell plasticity. Bone marrow derived stem cells were the first adult stem cells shown to have multilineage potential. Since, several reports have been published indicating that cells from other tissues; fat, muscle, connective tissue e.g., possess potential to differentiate into lineages distinct from their tissue of origin. The optimal cell type for use in tissue engineering applications should be easy to obtain, cultivate and store. The human dermal fibroblast is an easily accessible cell source, which after routine cell expansion gives a substantial cell yield from a small skin biopsy. Hence, the dermal fibroblast could be a suitable cell source for tissue engineering applications.The main aim of this thesis was to investigate the differentiation capacity of human dermal fibroblasts, and their possible applications in bone and cartilage tissue engineering applications. Human dermal fibroblasts were shown to differentiate towards adipogenic, chondrogenic, and osteogenic phenotypes upon subjection to specific induction media. Differentiation was seen both in unrefined primary cultures and in clonal populations (paper I). Fibroblasts could be used to create three-dimensional cartilage- and bone like tissue when grown in vitro on gelatin microcarriers in combination with platelet rich plasma (paper II). 4 weeks after in vivo implantation of osteogenic induced fibroblasts into a fracture model in athymic rats, dense cell clusters and viable human cells were found in the gaps, but no visible healing of defects as determined by CT-scanning (paper III). After the induction towards adipogenic, chondrogenic, endotheliogenic and osteogenic lineages, gene expression analysis by microarray and quantitative real-time-PCR found several master regulatory genes important for lineage commitment, as well as phenotypically relevant genes regulated as compared to reference cultures (paper IV). In conclusion, results obtained in this thesis suggest an inherent ability for controllable phenotype alteration of human dermal fibroblasts in vitro. We conclude that dermal fibroblasts could be induced towards adipogenic, chondrogenic, endotheliogenic or osteogenic novel phenotypes which suggest a genetic readiness of differentiated fibroblasts for lineage-specific biological functionality, indicating that human dermal fibroblasts might be a suitable cell source in tissue engineering applications.