| 21. |
- Back, Christina
(författare)
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The Legal Process in Child Sexual Abuse : Difficulties in confirming evidence and providing support
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall purpose of this thesis was to study the situation of such children in the legal process. In depth-interviews were carried out on ten children aged 8-18 years old. The interviews focused on the children´s experiences and perceptions of meeting with various professionals in the legal process. In-depth interviews were also conducted with nine parents of children who had been sexually abused and who had entered into a legal process. Parents described how they experienced the situation for their children as victims, but also their experiences as parents whose children participated in a legal process. Seven prosecutors with experience of cases where children were plaintiffs were also interviewed in this study.The interviews were analysed using Interpretative Phenomenological Analysis (IPA). This is an appropriate method to explore the participants´ life-world/personal-world and the individuals´ personal perceptions of objects or events, as opposed to an attempt to produce an objective account. In the first study (study I) on the children, five major themes emerged through the analysis: not being believed, making child sexual abuse visible, need for support, sanctions for offenders and lack of respect for the child´s integrity. Almost all of the children had a feeling of not being believed.In the study (study II) on the parents, three superordinate themes emerged from an analysis of the data: stigmatization, need for support in the parental role and transforming consequences to reality.Three themes emerged from prosecutors study (study III) difficulties with the evidence of crime, children´s special needs and children´s dependence on adults. The informants´ descriptions of how they perceived the children in the legal process were associated with their experience of the difficulty of finding proof of the crime.The aim of study IV was to identify and describe the obstacles that can prevent children from talking about sexual abuse in a police interview. Data consisted of 28 investigative interviews with children and 12 police interrogations with non-offending parents. Data interpretation and analysis were based on content analysis. The following categories were identified: not being believed/telling the truth, need for support and dependence on adults, guilt and shame, fear and difficulty in spatial and temporal characterization.The main conclusion of the thesis is that there are difficulties in confirming evidence when children who have suffered sexual abuse are involved in a legal process. It is also concluded that there is an absence of models with the aim to support children and parents going through the process.
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| 22. |
- Backteman, Karin, 1960-
(författare)
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T Cells and NK Cells in Coronary Artery Disease : Longitudinal and methodological studies in humans
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Coronary artery disease (CAD) is the leading cause of death worldwide and most often due to atherosclerosis. Atherosclerosis is a chronic inflammatory process that involves the arteries, inclouding those that supply blood to the heart muscle. Although inflammation is an important contributing factor to atherosclerosis, the mechanisms are not fully understood. One mechanism contributing to atherogenesis may involve some infectious microorganisms such as cytomegalovirus (CMV). In atherosclerosis, the arterial wall becomes infiltrated with lipids followed by different types of leukocytes and inflammatory mediators (atherogenesis). Leukocytes recirculate continuously between the blood and lymphoid organs, such as lymph nodes, where the adaptive immune response is started and regulated.The general aim of this thesis was to increase the understanding of associations between lymphocyte populations and different conditions of CAD (unstable and stable). To assess changes over time, a longitudinal follow up design was mostly used. Therefore, also perspectives of longitudinal variation were included in the thesis.Paper I showed that flow cytometric evaluation of lymphocyte populations is a robust technique that can be used in longitudinal studies, both in clinical and research settings. It was also shown that the time of sampling over the year did not have a major impact on the findings.In paper II, thoracic lymph nodes were investigated to assess whether CAD-associated changes were more prominent in comparison with blood. As expected, there were several major differences in lymphocyte composition between lymph nodes and blood. However, the analysis of thoracic lymph nodes did not reveal any further changes that were not detected in blood. Thus, blood is still the most reliable compartment for studies of lymphocyte populations in CAD since it is not possible to examine the local findings in the artery wall.Natural killer (NK) cells are innate lymphocytes with both regulatory and effector functions. In paper II and III we confirmed previous findings that CAD patients have lower proportions of NK cells in blood. However, the NK subtype and cytokine profile (paper III, measured by subtype markers and intra-cellular cytokine staining) did not differ between patients and controls. During a 12-month follow-up, the proportions of NK cells increased, although not in all patients. Failure to reconstitute NK cell levels was associated with several components of the metabolic syndrome and with a persistent low-grade inflammation as measured by plasma IL-6 levels. The findings support the notion of a protective role for NK cells in inflammation.CD4+ but not CD8+ T cells were significantly increased in patients with both unstable and stable conditions compared with healthy individuals (paper IV). Subpopulations of CD4+ T cells (CD4+CD28null) have previously been associated with CAD. However, we show that CD28null and CD28null57+ cells within the CD4+ and CD8+ T cell populations were similar in CAD patients and healthy controls. Instead, CMV seropositivity was the major determinant of expanded CD28null and CD57+ T cell fractions in both patients and healthy individuals. During the 1 year follow up the proportion of CD4+CD28null and CD8+CD28null cells increased in patients, which may reflect an accelerated immunological ageing occurring after the cardiac event.
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| 23. |
- Bagheri, Maryam
(författare)
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Neuroprotective Effect of Genistein : Studies in Rat Models of Parkinson’s and Alzheimer’s Disease
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parkinson’s disease (PD) and Alzheimer’s disease (AD) are neurodegenerative disorders that mainly affect the elderly population. It is believed that oxidative stress is involved in development of both these diseases and that estrogen deficiency is a risk factor for development of AD. Genistein is a plant-derived compound that is similar in structure to estrogen and has anti-oxidative properties. The general objective of the present research was to evaluate the effects of genistein on neurodegeneration in rat models of PD and AD.Using a rat model of PD, we found that a single intraperitoneal dose of genistein 1 h before intrastriatal injection of 6-hydroxydopamine (6-OHDA) attenuated apomorphine-induced rotational behavior and protected the neurons of substantia nigra pars compacta against 6-OHDA toxicity.To produce an animal model of AD, we injected Aβ1–40 into the hippocampus of rats. Using groups of these Aβ1–40-lesioned animals, the involvement of estrogen receptors (ERs) was evaluated by intracerebroventricular injection of the estrogen receptor antagonist fulvestrant, and the role of oxidative stress was studied by measuring levels of malondialdehyde (MDA), nitrite, and superoxide dismutase (SOD) activity. The results showed that intrahippocampal injection of Aβ1–40 caused the following: lower spontaneous alternation score in Y-maze tasks, impaired retention and recall capability in the passive avoidance test, and fewer correct choices and more errors in a radial arm maze (RAM task), elevated levels of MDA and nitrite, and a signiHcant reduction in SOD activity in the brain tissue. Furthermore, hippocampus in theses rats exhibited Aβ1–40 immunoreactive aggregates close to the lateral blade of the dentate gyrus (DGlb), extensive neuronal degeneration in the DGlb, high intracellular iNOS+ and nNOS+ immunoreactivity, and extensive astrogliosis.Genistein pretreatment ameliorated the Aβ-induced impairment of short-term spatial memory, and this effect occurred via an estrogenic pathway and through attenuation of oxidative stress. Genistein also ameliorated the degeneration of neurons, inhibited the formation of Aβ1–40-positive aggregates, and alleviated Aβ1–40-induced astrogliosis in the hippocampus.
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| 24. |
- Barrenäs, Fredrik, 1981-
(författare)
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Bioinformatic identification of disease associated pathways by network based analysis
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many common diseases are complex, meaning that they are caused by many interacting genes. This makes them difficult to study; to determine disease mechanisms, disease-associated genes must be analyzed in combination. Disease-associated genes can be detected using high-throughput methods, such as mRNA expression microarrays, DNA methylation microarrays and genome-wide association studies (GWAS), but determining how they interact to cause disease is an intricate challenge. One approach is to organize disease-associated genes into networks using protein-protein interactions (PPIs) and dissect them to identify disease causing pathways. Studies of complex disease can also be greatly facilitated by using an appropriate model system. In this dissertation, seasonal allergic rhinitis (SAR) served as a model disease. SAR is a common disease that is relatively easy to study. Also, the key disease cell types, like the CD4+ T cell, are known and can be cultured and activated in vitro by the disease causing pollen.The aim of this dissertation was to determine network properties of disease-associated genes, and develop methods to identify and validate networks of disease-associated genes. First, we showed that disease-associated genes have distinguishing network properties, one being that they co-localize in the human PPI network. This supported the existence of disease modules within the PPI network. We then identified network modules of genes whose mRNA expression was perturbed in human disease, and showed that the most central genes in those network modules were enriched for disease-associated polymorphisms identified by GWAS. As a case study, we identified disease modules using mRNA expression data from allergen-challenged CD4+ cells from patients with SAR. The case study identified and validated a novel disease-associated gene, FGF2 using GWAS data and RNAi mediated knockdown.Lastly, we examined how DNA methylation caused disease-associated mRNA expression changes in SAR. DNA methylation, but not mRNA expression profiles, could accurately distinguish allergic patients from healthy controls. Also, we found that disease-associated mRNA expression changes were associated with a low DNA methylation content and absence of CpG islands. Specifically within this group, we found a correlation between disease-associated mRNA expression changes and DNA methylation changes. Using ChIP-chip analysis, we found that targets of a known disease relevant transcription factor, IRF4, were also enriched among non CpG island genes with low methylation levels.Taken together, in this dissertation the network properties of disease-associated genes were examined, and then used to validate disease networks defined by mRNA expression data. We then examined regulatory mechanisms underlying disease-associated mRNA expression changes in a model disease. These studies support network-based analyses as a method to understand disease mechanisms and identify important disease causing genes, such as treatment targets or markers for personalized medication.
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| 25. |
- Bastami, Salumeh, 1967-
(författare)
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Practical and clinical use of opioids
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pain is a common symptom of a number of conditions including cancer and one of the most frequent reasons for seeking healthcare. Acute and chronic pain result in considerable discomfort with a detrimental impact on the quality of life. Opioids are the mainstay of pain management for many patients with severe pain. Opioids are, unfortunately, also commonly abused drugs, and are well-represented in forensic toxicology investigations.Side effects related to the central nervous system are the major reasons fordiscontinuation of opioid treatment. In this thesis, we tested the hypothesis that local analgesic treatment by opioids, without the usual opioid-related side effects, could be a potential alternative to systemic opioid treatment. We examined the analgesic effect of topically applied morphine in a randomized, double blind, cross over study in patients with painful leg ulcers. Significant reduction of pain was obtained after application of both morphine and placebo gel. Morphine reduced pain more than placebo but the difference was not statistically significant. However, morphine could reduce pain considerably more than placebo in those cases where VAS (Visual analog scale) was higher initially.Another issue with opioid therapy is the substantial individual variability in response to opioids including morphine and tramadol. We investigated the significance of UGT2B7, CYP2D6, OPRM1 and ABCB1 polymorphisms for pharmacokinetic and pharmacodynamic properties of morphine and tramadol. We showed that genetic variants in CYP2D6 and UGT2B7 have an important role in the metabolism of tramadol and morphine respectively. While the role of SNPs in ABCB1 remained unclear, genetic variants in OPRM1 gene were correlated with the required dose of morphine. Taken together, these findings suggest that genotypes should be taken into consideration when interpreting clinical pharmacology and forensic toxicology results.Opioids, besides their analgesic properties, have other pharmacological effects including effects on immune system. We evaluated potential differences between commonly used opiates with regard to their effect on the immune system. We found an inhibition of cytokine release, in the order of potency as follows: tramadol > ketobemidone >morphine >fentanyl. All opioids with the exception of fentanyl were capable of inhibiting production of mRNAs for TNF-alpha and IL-8. Further studies are needed to understand the clinical implications of the observed immunosuppressive effects of opioids and to improve opioid treatment strategies in patients with cancer.Here, we have found that individual genotype matters and affects the individual response. Further research is warranted to tailor individualized treatment. Personalized medicine has increased in importance and will hopefully in the near future become standard procedure to improve and predict the outcome of treatment by opioids.
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| 26. |
- Bendrik, Christina, 1964-
(författare)
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Angiogenesis regulation in hormone dependent breast- and ovarian cancer
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Angiogenesis is a key event in tumor progression and a rate-limiting step in the establishment of a clinical cancer disease. The net balance of pro- and anti-angiogenesis mediators in the tissue dictates the angiogenic phenotype of a tumor. Matrix metalloproteinases (MMPs) are major regulators of extracellular matrix turnover and have for long been associated with pro-tumorigenic activities due to their tissue degradation capacities. However, broad-spectra MMP inhibitors as anti-tumor therapy in clinical trials have failed, and it has now become evident that several MMPs may induce biological activities beneficial to the host, such as suppressed angiogenesis. In this thesis the protective role of specific MMPs in breast and ovarian tumor tissues was further demonstrated.The process of angiogenesis is essential for physiological functions in the female reproductive tract, where sex steroids regulate new blood vessel formation and regression in each cycle. Despite progress made during the past years, our knowledge in sex steroid regulation of angiogenesis in hormone-dependent tumor tissues remains limited. Tamoxifen is a cornerstone in the treatment of estrogen receptor (ER)-positive breast cancer. The therapeutic value of tamoxifen in the treatment of ER-positive ovarian cancer is to date less investigated. The results presented in this thesis suggest that tamoxifen may induce anti-tumorigenic responses in ER-positive ovarian cancer by means of both anti-proliferative and anti-angiogenic mechanisms. In experimental models of human ovarian cancer in vitro and in vivo, tamoxifen treatment increased extracellular levels of MMP-9 and enhanced generation of the angiogenesis inhibitor endostatin which resulted in significantly decreased angiogenesis and tumor growth. Low levels of MMP-9 and endostatin in ascites collected from ovarian cancer patients suggest a possibility to therapeutically enhance MMP-9 by administration of tamoxifen, and thereby counteract angiogenesis in ovarian tumors by increased generation of anti-angiogenesis fragments, such as endostatin.The significance of enhanced MMP activities in tumor tissues was further investigated by experimental models of intratumoral MMP gene transfer to human breast tumor xenografts, which were assessed by using microdialysis. Treatment of tumors with MMP-9 or MMP-3 resulted in dose-dependent inhibition of tumor growth. Low dose of either MMP induced tumor stasis whereas a higher dose induced significant tumor regression. MMP-9 and tamoxifen exerted synergistic therapeutic effects on breast tumor angiogenesis and growth whereas gene transfer of the MMP-inhibitor TIMP-1 counteracted the beneficial effects induced by tamoxifen.Further on, we confirm the pro-angiogenic potential of estradiol by demonstrating a significant correlation between local levels of estradiol and the pro-angiogenic cytokine IL-8 in normal human breast tissues and in ER/PgR-positive breast cancers of women. Estradiol-induced IL-8 secretion was additionally confirmed in normal human whole breast biopsies in culture and in experimental human breast cancer in vitro and in vivo.In conclusion, the results of this thesis may hopefully increase the overall understanding of several mechanisms involved in angiogenesis regulation and may additionally be useful in the development of novel approaches for targeted therapy in the treatment of hormone-sensitive breast- and ovarian cancer.
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| 27. |
- Berg, Katarina, 1959-
(författare)
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Patients’ perspectives on recovery from day surgery
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A large number of elective surgical patients in Sweden and elsewhere have their surgical procedure performed in a day surgery context. The surgical care event, with its postoperative surveillance, is brief at the surgery unit and patients are discharged home with the intention that they should manage postoperative recovery mainly themselves. However, several patients attest to being in an exposed situation when assuming responsibility for recovery at home. The overall aim of this thesis was to attain comprehensive knowledge of postoperative recovery following day surgery from a patient perspective.A questionnaire, the Post-discharge Surgical Recovery scale, was translated into Swedish and evaluated regarding its psychometric properties in a Swedish context. A sample of 607 day surgery patients who had undergone orthopaedic, general or gynaecological surgery self-rated their recovery at postoperative Days 1, 7 and 14 using the Post-discharge Surgical Recovery scale and the Quality of Recovery-23. Health-related quality of life was assessed before and 30 days after the surgical procedure, using the EQ-5D. In a second sample, 31 patients were interviewed in their homes regarding their recovery after day surgery. The interviews were conducted on postoperative Days 11-37, and focused on the meaning of recovery, self-care and perceptions of recovery. Data were explored by means of a phenomenographic analysis.The Post-discharge Surgical Recovery scale showed satisfactory psychometric properties when used among Swedish day surgery patients. Following discharge, recovery included both physical and emotional perspectives. Recovery varied, and influencing factors were found to be type of surgery, age, perceived health and emotional status on the first postoperative day. Orthopaedic patients had a more protracted recovery process compared to general surgery and gynaecological patients, along with more postoperative pain and lower health-related quality of life. Patients perceived that postoperative recovery comprised different internal and external factors and a large amount of responsibility regarding their recovery and surgical outcome. To be prepared for recovery at home, patients wanted knowledge and understanding about the normal range of recovery following their specific surgical procedure, and needed support from different sources in their surroundings.This thesis provides insight into day surgery patients’ postoperative situation. Based on the studies, individualized and well thought-out support appears favourable in order to have confident and well prepared patients at home. In contrast to smooth and easy patient care at the surgery unit, the postoperative phase seems to be a weak link in the day surgical continuity of patient care. Postoperative care needs to be further improved to increase quality and patients’ overall satisfaction with the day surgical experience. Attention should be paid to patients’ physical and emotional resources and needs.
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| 28. |
- Berg, Svante, 1953-
(författare)
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On Total Disc Replacement
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Low back pain consumes a large part of the community’s resources dedicated to health care and sick leave. Back disorders also negatively affect the individual leading to pain suffering, decreased quality-of-life and disability. Chronic low back pain (CLBP) due to degenerative disc disease (DDD) is today often treated with fusion when conservative treatment has failed and symptoms are severe. This treatment is as successful as arthroplasty is for hip arthritis in restoring the patient’s quality of life and reducing disability. Even so, there are some problems with this treatment, one of these being recurrent CLBP from an adjacent segment (ASD) after primarily successful surgery. This has led to the development of alternative surgical treatments and devices that maintain or restore mobility, in order to reduce the risk for ASD. Of these new devices, the most frequently used are the disc prostheses used in Total Disc Replacement (TDR).This thesis is based on four studies comparing total disc replacement with posterior fusion. The studies are all based on a material of 152 patients with DDD in one or two segments, aged 20-55 years that were randomly treated with either posterior fusion or TDR.The first study concerned clinical outcome and complications. Follow-up was 100% at both one and two years. It revealed that both treatment groups had a clear benefit from treatment and that patients with TDR were better in almost all outcome scores at one-year follow-up. Fusion patients continued to improve during the second year. At two-year follow-up there was a remaining difference in favour of TDR for back pain. 73% in the TDR group and 63% in the fusion group were much better or totally pain-free (n.s.), while twice as many patients in the TDR group were totally pain free (30%) compared to the fusion group (15%).Time of surgery and total time in hospital were shorter in the TDR group.There was no difference in complications and reoperations, except that seventeen of the patients in the fusion group were re-operated for removal of their implants.The second study concerned sex life and sexual function. TDR is performed via an anterior approach, an approach that has been used for a long time for various procedures on the lumbar spine. A frequent complication reported in males when this approach is used is persistent retrograde ejaculation. The TDR group in this material was operated via an extra-peritoneal approach to the retroperitoneal space, and there were no cases of persistent retrograde ejaculation. There was a surprisingly high frequency of men in the fusion group reporting deterioration in ability to have an orgasm postoperatively.Preoperative sex life was severely hampered in the majority of patients in the entire material, but sex life underwent a marked improvement in both treatment groups by the two-year follow-up that correlated with reduction in back pain.The third study was on mobility in the lumbar spinal segments, where X-rays were taken in full extension and flexion prior to surgery and at two-year follow-up. Analysis of the films showed that 78% of the patients in the fusion group reached the surgical goal (non-mobility) and that 89% of the TDR patients maintained mobility.Preoperative disc height was lower than in a normative database in both groups, and remained lower in the fusion group, while it became higher in the TDR group. Mobility in the operated segment increased in the TDR group postoperatively. Mobility at the rest of the lumbar spine increased in both treatment groups. Mobility in adjacent segments was within the norm postoperatively, but slightly larger in the fusion group.In the fourth study the health economics of TDR vs Fusion was analysed. The hospital costs for the procedure were higher for patients in the fusion group compared to the TDR group, and the TDR patients were on sick-leave two months less.In all, these studies showed that the results in the TDR group were as good as in the fusion group. Patients are more likely to be totally pain-free when treated with TDR compared to fusion. Treatment with this new procedure seems justified in selected patients at least in the short-term perspective. Long-term follow-up is underway and results will be published in due course.
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| 29. |
- Berglund, Björn, 1983-
(författare)
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Deliberations on the impact of antibiotic contamination on dissemination of antibiotic resistance genes in aquatic environments
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The great success of antibiotics in treating bacterial infectious diseases has been hampered by the increasing prevalence of antibiotic resistant bacteria. Not only does antibiotic resistance threaten to increase the difficulty in treating bacterial infectious diseases, but it could also make medical procedures such as routine surgery and organ transplantations very dangerous to perform. Traditionally, antibiotic resistance has been regarded as a strictly clinical problem and studies of the problem have mostly been restricted to a clinical milieu. Recently, non-clinical environments, and in particular aquatic environments, have been recognised as important factors in development and dissemination of antibiotic resistance. Elevated concentrations of antibiotics in an environment are likely to drive a selection pressure which favours resistant bacteria, and are also believed to promote horizontal gene transfer among the indigenous bacteria. Antibiotic resistance genes are often located on mobile genetic elements such as plasmids and integrons, which have the ability to disseminate among taxonomically unrelated species. The environmental bacteria can thus serve as both reservoirs for resistance and hot spots for the development of new antibiotic resistance determinants.There is still a lack of data pertaining to how high antibiotic concentrations are necessary to drive a selection pressure in aquatic environments. The aim of this thesis is to determine the effect of high and low concentrations of antibiotics on environmental bacterial communities from different aquatic environments. In the studies performed, antibiotics were measured using liquid chromatography-mass spectrometry. Bacterial diversity and evenness were assessed using molecular fingerprints obtained with 16S rRNA gene-based denaturing gradient gel electrophoresis, and antibiotic resistance genes and class 1 integrons were quantified using real-time PCR.Water and sediment samples were collected from different rivers and canals in Pakistan. The environments differed in anthropogenic exposure from undisturbed to heavily contaminated. A general trend could be observed of high concentrations of antibiotics correlating to elevated concentrations of antibiotic resistance genes and integrons. Extremely high concentrations of antibiotic resistance genes and integrons were found in the sediments downstream of an industrial drug formulation site, which likely correlated to the high load of antibiotics found in the water. Antibiotic and antibiotic resistance gene concentrations were also shown to increase downstream of Ravi river, which flows through Lahore, a city of more than 10 million inhabitants. Rivers not impacted by anthropogenic contamination were found to contain antibiotics and resistance gene concentrations of similar levels as in Europe and the U.S. Similar measurements were performed in the Swedish river Stångån. The concentrations of antibiotic resistance genes and class 1 integrons were shown to increase in the river after it had passed, and received urban wastewater effluent from the city of Linköping.A series of constructed wetlands were exposed to a mixture of different antibiotics at environmentally relevant concentrations over a few weeks. The antibiotic exposure did not observably affect the bacterial diversity or integron concentrations. Antibiotic resistance genes were found at low background concentrations, but the antibiotic exposure did not observably affect the concentrations. The constructed wetlands were also found to reduce most antibiotics at levels comparable to conventional wastewater treatment schemes, suggesting that constructed wetlands may be useful supplementary alternatives to conventional wastewater treatment.To investigate the effect of antibiotics on an uncontaminated aquatic environment in a more controlled setting, microcosms were constructed from lake water and sediments and subsequently exposed to varying concentrations of antibiotics (ranging from wastewater-like concentrations to 1,000 times higher). The water and sediments were gathered from the lake Nydalasjön, near Umeå, which is not exposed to urban waste. While antibiotic resistance genes and class 1 integrons were found in the lake sediments, no increase in the concentrations of these genes could be observed due to the antibiotic additions.In conclusion, although antibiotic resistance genes and integrons are part of the environmental gene pool, low concentrations of antibiotics do not seem to immediately impact their prevalence. However, aquatic environments exposed to anthropogenic waste do exhibit elevated levels of antibiotic resistance genes and integrons. Aquatic environments heavily polluted with antibiotics also clearly display correspondingly high concentrations of antibiotic resistance genes and integrons. These results clearly indicate the necessity to keep down pollution levels as well as the need to establish the range of antibiotic concentrations which do promote resistance. This must be done in order to enable risk assessments and to establish acceptable levels of antibiotic pollution. It should also be stressed that more research is required to elucidate what effect low levels of antibiotic exposure has on environmental bacterial communities.
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| 30. |
- Bergstrand, Sara, 1978-
(författare)
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Preventing pressure ulcers by assessment of the microcirculation in tissue exposed to pressure
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to combine optical methods into a system with the ability to simultaneously measure blood flow changes at different tissue depths. The goal of such a system was to reveal vascular mechanisms relevant to pressure ulcer etiology under clinically relevant conditions and in relation to the evaluation of pressure-redistribution support surfaces.This thesis consists of four quantitative, cross-sectional studies measuring blood flow responses before, during, and after pressure exposure of the sacral tissue. Two optical methods – photoplethysmography and laser Doppler flowmetry – were combined in a newly developed system that has the ability to discriminate blood flows at different tissue depths. Studies I and II explored blood flow responses at different depths in 17 individuals. In Study I the blood flow was related to tissue thickness and tissue compression during pressure exposure of ≥ 220 mmHg. In Study II, the sacral tissue was loaded with 37.5 mmHg and 50.0 mmHg, and the variation in blood flow was measured. Studies III and IV included 42 healthy individuals < 65 years, 38 healthy individuals ≥ 65 years, and 35 patients ≥ 65 years. Study III included between-subject comparisons of blood flow and pressure between individuals in the three study groups lying in supine positions on a standard hospital mattress. Study IV added within-subject comparisons while the individual was lying on four different types of mattress. The studies explored the vascular phenomena pressure-induced vasodilation (PIV) and reactive hyperemia (RH).The most common blood flow response to tissue exposure in this thesis was PIV, although a decrease in blood flow (a lack of PIV) was observed in some individuals. The patients tended to have higher interface pressure during pressure exposure than the healthy groups but no differences in blood flow responses were seen. Our results showed that pressure levels that are normally considered to be harmless could have a significant effect on the microcirculation in different tissue structures. Differences in individual blood flow responses in terms of PIV and RH were seen, and a larger proportion of individuals lacked these responses in the deeper tissue structures compared to more superficial tissue structures.This thesis identified PIV and RH that are important vascular mechanisms for pressure ulcer development and revealed for the first time that PIV and RH are present at different depths under clinically relevant conditions. The thesis also identified a population of individuals not previously identified who lack both PIV and RH and seem to be particularly vulnerable to pressure exposure. Further, this thesis has added a new perspective to the microcirculation in pressure ulcer etiology in terms of blood flow regulation and endothelial function that are anchored in clinically relevant studies. Finally, the evaluation of pressureredistribution support surfaces in terms of mean blood flow during and after tissue exposure was shown to be unfeasible, but the assessment of PIV and RH could provide a new possibility for measuring individual physiological responses that are known to be related to pressure ulcer development.
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