| 1. |
- Bäckström, Josefin, 1977-
(författare)
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Family Members of Patients with Burns : Experiences of a Distressful Episode
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A severe burn is a trauma associated with long lasting consequences, not only for the survivor but also for the family. Although it is recognized that family members are central in providing social support for the patients, previous research has not focused extensively on this group. The aims of this thesis were to increase knowledge about psychological symptoms and health-related quality of life (HRQoL) in family members of patients with burns, as well as to explore their experiences of burn care and rehabilitation. The research questions were approached using quantitative and qualitative methods.The results showed that most family members demonstrate normal to mild levels of psychological symptoms, while one third demonstrate moderate to severe symptoms during care. The symptoms decreased over time and could be predicted to a certain degree by early symptoms.Further, family members’ report of HRQoL is similar to that of the general population. An improvement is seen over time and HRQoL could be predicted in part by earlier life events and psychological symptoms.Family members’ experiences were explored in an interview study. Qualitative content analysis revealed that the time in hospital is stressful, although there were experiences of a positive character. Family members might benefit from being cared for in a more individualized way. The communication between health care providers and the family members could be improved.Finally, a qualitative content analysis revealed that family members’ experiences and views concerning support is highly individual. There were experiences of sufficient support as well as lack of professional support. Treatment of family members should be modified according to personal circumstances, and it is important to actively include family members in the care process, both before and after discharge.In summary, being a family member of a burn survivor is a distressful experience, not only during care but in many cases also after discharge. The treatment of family members within burn care should be individualized. Some persons are more vulnerable than others and it might be possible to identify those in need of support while care is still ongoing.
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| 2. |
- Fredriksson, Camilla, 1969-
(författare)
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Keratinocytes in tissue engineering of human skin: invitro and in vivo studies
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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. 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.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.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.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.
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| 3. |
- Hakelius, Malin, 1965-
(författare)
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Interactions between Malignant Keratinocytes and Fibroblasts : Studies in Head and Neck Squamous Cell Carcinoma
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Carcinoma growth requires a supportive tumor stroma. The concept of reciprocal interactions between tumor and stromal cells has become widely acknowledged and the connective tissue activation seen in the malignant process has been likened to that of a healing wound. Little is, however, known about the specific characteristics of these interactions, distinguishing them from the interplay occurring between epithelial and stromal cells in wound healing. In order to study differences in the humoral effects of malignant and benign epithelial cells on fibroblasts, we used an in vitro coculture model with human oral squamous cell carcinoma cells (SCC) or normal oral keratinocytes (NOK) on one side of a semi-permeable membrane and fibroblasts seeded in gels on the other. Pro-collagens α1(I) and α1(III) were more downregulated in NOK cocultures compared to SCC cocultures. IL-1α was identified as a major keratinocyte-derived soluble factor behind the effects observed. We concluded that SCC are less antifibrotic compared to NOK. There was also a differential expression among enzymes involved in ECM turnover. The urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) were both upregulated by NOK, but not by SCC. Here, rIL-1ra caused further upregulation of PAI-1. Global gene expression in fibroblasts was assessed using Affymetrix™ arrays. In total, 82 transcripts were considered differentially expressed; 52 were up- and 30 were downregulated in SCC compared to NOK cocultures. Among the differentially expressed genes there was an enrichment of genes related to collagens and to a nonspecific, innate-type response. The innate response marker pentraxin (PTX3) was upregulated by keratinocyte-derrived IL-1α in both NOK and SCC cocultures. We observed a considerably higher IL-1α / IL-1ra quotient in SCC cocultures, however, while PTX3 mRNA upregulation was higher in SCC cocultures, there was no difference in the level of PTX3 secreted protein. Taken together, we concluded that NOK and SCC regulate genes important for ECM composition and for the innate immune-response differentially. IL-1α was identified as one important mediator of the observed effects. In general, SCC appeared to be more profibrotic in their effects on fibroblasts.
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| 4. |
- Kiwanuka, Elizabeth, 1983-
(författare)
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CCN2 – Keratinocyte Interactions In Vitro and In Vivo
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cutaneous wound healing is a complex process involving the migration of inflammatory cells to the wound site, deposition of extracellular matrix, and the reestablishment of an intact epithelial barrier. Re-epithelialization depends on the proliferation and directional migration of keratinocytes from the wound edges. Initially, keratinocytes migrate over a provisional wound matrix that is rich in fibronectin, and as the wound heals the provisional matrix becomes replaced by one consisting of collagen and proteoglycans. Re-epithelialization is tightly regulated by a variety of peptides such as growth factors, cytokines and proteases, and abnormalities may result in chronic non-healing wounds or hypertrophic scars. CCN2 (Connective Tissue Growth Factor) is a multifunctional protein with effects on cells and their interactions with the connective tissue. CCN2 is expressed in a variety of cell types and regulates numerous cell functions including proliferation, differentiation, adhesion, migration and stimulation of collagen production. While the importance of CCN2 for the fibrotic response has been well studied, its involvement in keratinocyte function has not yet been fully explored. Using an in vivo wound model, the expression of CCN2 was captured at the leading keratinocyte edge during re-epithelialization. In vitro, exogenous addition of CCN2 to human keratinocyte cultures promoted keratinocyte migration. Subsequently, integrin a5b1 was identified as an important mediator of CCN2 enhancement of keratinocyte adhesion to fibronectin. CCN2 activated the FAK-MAPK signaling pathway, and pretreatment with MEK1 specific inhibitor PD98059 markedly reduced CCN2-promoted keratinocyte migration. In vitro, CCN2 expression was induced by TGF-β1. Compared with inhibiting the SMAD pathway, blocking MAPK was more effective in reducing TGF-β1-induced CCN2 mRNA and protein expression. In addition, CCN2-induced keratinocyte spreading required FAK. Treatment with CCN2 led to actin disassembly and altered the activity of the Rho proteins and p190RhoGAP in keratinocytes. Furthermore, Cdc42 mediated CCN2-induced cell polarity. In conclusion, using in vivo and in vitro models, CCN2 was shown to regulate keratinocyte function by promoting keratinocyte adhesion, spreading and migration. A complete understanding of CCN2 expression in keratinocytes is crucial in order to develop novel therapies for wound healing.
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| 5. |
- Lindahl, Andreas, 1974-
(författare)
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Neuroendocrine Stress Response after Burn Trauma
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Some aspects of the stress response during acute intensive care for severe burns are described and quantified by measuring hormonal and neuroendocrine patterns and relating these to organ function in the short term. This includes an assessment of whether there are markers for the severity of stress that are better than conventional descriptors of the severity of a burn in predicting failing organ function.P-CgA after a major burn injury is an independent and better predictor of organ dysfunction assessed as SOFA score than the traditionally used TBSA% burned. The results also suggest that the extent of neuroendocrine activation is related to organ dysfunction, and this motivates a more extensive effort to evaluate P-CgA as a prognostic marker with respect to mortality and long-term outcome.P-NT-proBNP exhibited a complex pattern with considerable inter-individual and day-to-day variations. Values of P-NT-proBNP were related to size of burn, water accumulation and systemic inflammatory response. A considerable covariation with trauma response and SOFA scores was observed in day by day analyses, but with weight change only on day 2.Maximum P-NT-proBNP showed a stronger correlation with SOFA score on day 14, with mortality, and with LOS, than did age and TBSA% burned. High values were also independent predictors of all subsequent SOFA scores up to two weeks after injury.P-NT-proBNP and NT-proANP reflect and predict organ function after burn injury similarly, notwithstanding a significantly larger intra-individual variability for P-NT-proBNP. P-NT-proBNP, but not NT-proANP, reflects the systemic inflammatory trauma response.Free cortisol concentration was related to the size of burns, as was the circadian cortisol rhythm. This effect of burn size was, at least in part, related to its effect on organ function.This thesis points to the fact that the stress response is richly interwoven, and cannot be adequately assessed by one biomarker only. All biomarkers studied here can be viewed as representing efferent limbs of the stress reaction, and they would need to be supplemented by biomarkers representing individual physiologic responses that follow the stress signaling.
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| 6. |
- Lindqvist, Aron, 1964-
(författare)
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Hand Injury from Powered Wood Splitters
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this study on hand injury from powered wood splitters was to describe injury epidemiology and anatomy, to rate injury severity, to evaluate the outcome after injury and to describe factors of possible importance for the occurrence of injury.By searching a computerized patient registry, 131 patients injured by wood splitters from 1995 to 2001 were identified. Information was obtained from hospital records and radiographs, a written questionnaire and a structured telephone interview. Injury severity was rated according to the Hand Injury Severity Scoring System (HISS system) and the Injury Severity Score (ISS). Outcome was evaluated with the Disabilities of the Arm, Shoulder and Hand outcome questionnaire (DASH) and, in 26 of the most severely injured patients, with the Sollerman test.Forty-six percent of the injuries occurred during April or May. Wedge splitters caused 82 % of all injuries and most often injured the index finger, while screw splitters caused 18 % of all injuries and most often injured the metacarpus. Screw splitters caused palmar perforation and thumb avulsion. Sixty-three percent of all patients had an amputation or devascularising injury. The reliability of HISS rating was good. The mean Hand Injury Severity Score (HISS) was 63 which is equivalent to a severe hand injury. The mean ISS was 3.7. Nineteen percent of patients had minor, 31 % had moderate, 23 % had severe and 27 % had major injury according to the HISS system. Children had more severe injuries than adults. There was no significant difference regarding HISS or DASH scores between wedge and screw splitter injuries. The mean DASH score was 15, indicating moderate residual sequelae, but patients without sequelae and patients with grave sequelae were found in all HISS severity grades. There was a weak but significant correlation between the HISS and DASH scores. The mean Sollerman score in the injured hand was 66, indicating significantly impaired hand function. Twenty-nine percent of splitters were home-made. Very few machines had the safety measures required by European Standards. Children were present during splitting in at least 15 % of cases. Not being alone at the machine was one cause of wedge splitter injury. Glove use was one cause of screw splitter injury.Hand injury from powered wood splitters is a significant problem. Many of the injuries are severe, and cause long term sequels and impairment of hand function. Prevention is essential and should focus on unsafe machines and dangerous patterns of use.
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| 7. |
- Kouppis, Efthymios, 1982-
(författare)
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Mortality in women with personality disorders : Relationship to childbearing, ADHD and injuries treated in healthcare
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Personality disorders (PDs) constitute a significant global health problem, with approximately 8% of the population fulfilling diagnostic criteria for one or more PDs. PDs influence various healthcare aspects of an affected person’s life, leading to impaired functioning, suffering, and a lower quality of life. Persons with one or more PDs die earlier than the background population of natural and unnatural causes. They also consume a proportionately large amount of healthcare services and suffer more often from comorbid conditions. Furthermore, persons with PDs are prone to different injuries, such as accidents, self-inflicted injuries, and abuse. Women with PDs have a higher frequency of perinatal complications and problems in child rearing than the background population. Borderline PD (BPD), one of the most frequently diagnosed PDs, is much more often diagnosed in women than men despite the similar prevalence rates in both sexes.This thesis aimed to elucidate the effect of parity, comorbidity with ADHD, and the accumulated number of injuries treated in healthcare on mortality in women diagnosed with PD, all based on data from high-quality Swedish healthcare registers.Study I is a validation study of the Swedish National Patient Register (NPR) on the accuracy of registered PD diagnoses by scrutinizing records for patients diagnosed with PD. It was concluded that the NPR has good validity for diagnosing PD.Study II investigates the effect of childbearing on all-cause mortality in women with any PD. The study demonstrated that women with PD who have given birth have a lower all-cause mortality than those who did not.Study III assesses the effect of comorbid ADHD on mortality in women with BPD. No significant effects were detected.Study IV reports a positive association between the number of injuries and intoxications that required inpatient care, on the one hand, and death due to natural and unnatural causes, on the other, in women with PD.This thesis shows that register data from the NPR can assess the consequences of having PD for diverse aspects of life. Specifically, it revealed the beneficial association between being parous for the risk of death, the indifferent association of having a comorbid ADHD, and the aggravating association between death risk and being prone to repeated injuries requiring inpatient healthcare.
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| 8. |
- Low, Janina Francisca Aili, 1966-
(författare)
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It’s Not Just a Burn : Physical and Psychological Problems after Burns
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Survival after severe burns has improved in recent decades, but there is limited information on the course of recovery after surviving a burn and on factors that can affect recovery. The aims of this thesis were to investigate the occurrence of physical and psychological problems after burns, and to examine the consequences of psychological problems for the clinical management of burn patients. Three groups of consecutive patients who were treated at the Burn Unit at Uppsala University Hospital between 1980 and 2005 were included in the studies. The Burn Specific Health Scale (BSHS) was used for self-report of burn-specific aspects of health. Personality traits and coping strategies as psychological factors during recovery were examined with the Swedish universities Scales of Personality (SSP) and the Coping with Burns Questionnaire (CBQ). Presence of symptoms of posttraumatic stress were assessed with the Impact of Event Scale-Revised (IES-R), and the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) was used to determine the concurrent validity of the IES-R as a measure of Posttraumatic Stress Disorder (PTSD). Furthermore, the effect of pre-injury psychiatric morbidity on perceived health one year after injury was assessed. Both pruritus and nightmares were common problems after burns; 59% of the individuals in the study reported pruritus and 43% reported nightmares. Neuroticism-related personality traits and avoidant coping strategies were associated with an increased risk of having pruritus or nightmares. The presence of nightmares could be used as a screening tool for high scores in the IES-R. The IES-R was in turn shown to be a good, although overly inclusive, test for the diagnosis of PTSD. Pre-injury psychiatric morbidity predicted perceived outcome in six out of nine burn-specific health domains. These studies show that psychological factors and psychiatric morbidity affect outcome after burns.
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| 9. |
- Wikehult, Björn, 1950-
(författare)
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Use of Healthcare, Perceived Health and Patient Satisfaction in Patients with Burns
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 10. |
- Abu-Zidan, Fikri M.
(författare)
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Role of platelet-activating factor in sepsis and shock : an experimantal study
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To study the role of platelet-activating factor (PAF) on cardiovascular and pulmonary dysfunction in sepsis and shock.Design: Experimental study. Setting: Trauma research unit, university department of surgery, Sweden.Material: 76 juvenile domestic pigs. Interventions: The effects of a specific PAF receptor antagonist (BB-882) on haemodynamics and on PAF-induced haemodynamic changes were studied (n = 16). BB-882 was given as pretreatment in non-hypotensive Escherichia coli endotoxaemia (n = 9), during resuscitation after severe haemorrhagic shock (n = 7), hefore post-ischaemic shock which was induced by clamping the aorta above the coliac axis for 45 minutes (n = 8), and as pretreatment in post-haemorrhage septic shock: (n = 6). BB~882 groups were compared with controi groups having the same number of animals which received vehicle instead.Major outcome measures: Heart rate, intravascular pressures, cardiac output, pulmonary and systemic vascular resistance, arteriai blood gas tensions, lung thorax compliance, serum lactic acid and blood sugar concentrations, and packed cell volume.Results: BB-882 effectively counleracted the PAF-induced response on the mean systemic and pulmonary arteriai pressures. lt reduced the rise in pulmonary and systemic vascular resistance and improved the cardiac output in non-hypotensive and post-haemorrhage septic shock when given as pretreatment. lt reduced the hypertension in non-hypotensive sepsis and the hypotension in post-haemorrhage septic shock. BB-8B2 did not infiuence the endotoxin-induced hypoxia or reduced lung thorax compliance in non-hypotensive sepsis and post-haemorrhage septic shock. It did not improve the mean arterial pressure or the cardiac output in haemorrhagic shock alone but it reduced the systemic vascular resistanc'e and was associated with tachycardia and acidosis. It did not affect the post-ischaemic shock after clamping the aorta.Conclusion: PAF is a major mediator of the cardiovascular, but not pulmonary dysfunction in sepsis whether associated with shock or not, while its role on the cardiovascular dysfunction in haemorrhagic and post-ischaemic shock is small.
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