| 71. |
- Amirhosseini, Mehdi
(författare)
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Aseptic Loosening of Orthopedic Implants : Osteoclastogenesis Regulation and Potential Therapeutics
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aseptic loosening is the main cause of failure of orthopedic prostheses. With no pharmaceuticals to prevent or mitigate periprosthetic bone degradation, a surgery to replace the loose implant with a new one is the only choice to restore patients’ function. Most studies on mechanisms for aseptic loosening investigate wear debris particle-induced osteolysis. However, pathological loading conditions around unstable implants can also trigger osteoclast differentiation and bone loss.In the first study, global gene expression changes induced by mechanical instability of implants, and by titanium particles were compared in a validated rat model for aseptic loosening. Microarray analysis showed that similar signaling pathways and gene expression patterns are involved in particle- and instability-induced periprosthetic osteolysis with an early onset innate immune response as a hallmark of osteolysis induced by mechanical instability.Further, effects of potential therapeutics on restriction of excessive osteoclast differentiation were evaluated. Wnt signaling pathway is known to regulate bone remodeling. In the second study, effects of inactivation of glycogen synthase kinase 3 beta (GSK-3β), a negative regulator of canonical Wnt signaling, on instability-induced periprosthetic osteolysis were examined using our rat model for aseptic loosening. Inhibition of GSK-3β led to a decrease in osteoclast numbers in the periprosthetic bone tissue exposed to mechanical instability while osteoblast perimeter showed an increase. This was accompanied by higher bone volume fraction (BV/TV) in animals treated with the GSK-3β inhibitor.In the third study, potential beneficial effects of two selective inhibitors of cyclindependent kinase 8/19 (CDK8/19) on bone tissue were evaluated. CDK8/19 is a Mediator complex-associated transcriptional regulator involved in several signaling pathways. CDK8/19 inhibitors, mainly under investigation as treatments for tumors, are reported to enhance osteoblast differentiation and bone formation. We show in this study, for the first time, that inhibition of CDK8/19 led to marked suppression of osteoclast differentiation from bone marrow macrophages in vitro through disruption of the RANK signaling. In mouse primary osteoblasts downregulation of osteopontin mRNA, a negative regulator of mineralization, together with increased alkaline phosphatase activity and calcium deposition indicated that osteoblast mineralization was promoted by CDK8/19 inhibition. Moreover, local administration of a CDK8/19 inhibitor promoted cancellous bone regeneration in a rat model for bone healing.These studies contribute to better understanding of mechanisms behind mechanical instability-induced periprosthetic osteolysis and propose potential therapeutics to restrict bone loss with effects on both osteoclasts and osteoblasts.
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| 72. |
- Andén, Annika, 1950-
(författare)
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Outcomes from GPs' Consultations
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims. Patients’ consultations with GPs can deal with a wide range of conditions and problems. Generally, consultation outcomes have been considered in evaluations but outcome has a meaning for elaboration of care beyond the graduating role of quality and other evaluation instruments. Knowledge about outcomes is needed for understanding and development. The aim of this thesis was to investigate outcomes of GPs’ consultations as directly experienced by patients and GPs and to investigate connections between clinical strategies and presumed patient outcomes.Methods. First, concepts describing outcomes from patients’ and GPs’ viewpoints were developed from interviews in groups and individually. Secondly, based on this, questionnaires about the consultation outcomes were formulated. Then, patients and GPs answered questionnaires regarding the same recent consultation. The numbers of the different outcomes were counted and the experiences of outcomes from the same consultations were compared. Finally, another questionnaire including both the GP outcome questions and questions about the clinical situation and decisions made was answered by GPs.Results. Concepts describing consultation outcomes were brought forward. Cure/symptom relief, reassurance, patient understanding and satisfaction were used by both patients and GPs to describe outcome of consultations. Only patients described as outcomes a confirmation of their ideas and a change in self-perception. GPs, but not patients, described the patient outcomes in terms of check-up and coping. Besides this, GPs also described other outcomes that concerned relationship-building, a change of surgery routines and self-evaluation. Selfevaluation was related to a perceived collegial consensus about right and wrong. The concordance between GPs and patients assessing the same consultations was high for satisfaction, intermediate for patient understanding and low for belief in cure/symptom relief. Clinical strategies were linked to outcomes. Immediate problem solving was registered in about half the consultations. When immediate problem solving was registered the patients were supposed to be more reassured, satisfied and coped better than after gradual problem solving. With increasing psychosocial content of the consultation the GPs registered more dissatisfaction both for themselves and their patients.Conclusions. Change in self- perception was a prominent patient outcome. GPs’ self-evaluations ought to have the inherent possibility to serve as a basis for development of general practice.The entire map of the encountered outcome concepts can serve as a basis for further research and development. The mapping of concepts can be of help when prioritising. Knowledge about the total picture of consultation outcomes can help the GP to understand the patients’ worlds better. It can also contribute to a realistic picture of possible consultation outcomes. The GPs seemed to adjust their problem solving (immediate or gradual) to the registered problem and furthermore adjust the immediate problem solving, focusing either on the problem or on the patient as a person.
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| 73. |
- Ander, Stefan
(författare)
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Preservation of parathyroid function in thyroid and parathyroid surgery
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Preservation of normal parathyroid function and calcium homeostasis after operations on the thyroid and parathyroid glands is a difficult assignment in endocrine surgery, and it is crucial to minimise the risks of permanent postoperative hypoparathyroidism. The aim of this thesis was to study the vascular supply of the parathyroid glands and the revascularisation, growth, and function of transplanted parathyroid tissue, in order to add new information about parathyroid preservation.The microcirculation and blood supply of normal, hyperplas~c and adenomatous parathyroid glands were studied with laser Doppler flowmetry in 103 patients during operations on the thyroid and parathyroid glands. In normal parathyroid glands the blood flow was higher compared with that in hyperplastic glands and adenomas. Occlusion of the main trunks of the inferior and superior thyroid arteries reduced the blood flow by 35% and 25%, respectively. The reduction was similar in normal, hyperplastic, and adenomatous parathyroid glands. In 12 patients with single parathyroid adenomas, the increased concentration of parathyroid hormone (PTH) remained mainly unchanged despite appreciable reduction in blood flow. In 16 patients the microcirculation and macroscopic appearance of normal parathyroid glands located anteriorly on the thyroid lobe were analysed before and after dissection for in situ preservation. There was a poor correlation between reduction in blood flow and macroscopic appearance of the glands. Laser Doppler flowmetry (LDF) showed that the disturbed microcirculation often recovered 30-60 minutes after dissection for preservation.Parathyroid tissue obtained from 47 patients operated on for hyperparathyroidism was implanted subcutaneously in athymic mice. The processes of revascularisation, morphology, cell proliferation, and function of normal, hyperplastic, and adenomatous parathyroid tissue were studied at 2 and 4 days and 1, 4, 7 and 12 weeks after transplantation. Vessels were detected by monoclonal antibodies specific for mouse and human endothelial cells. The transplanted tissues were examined by light and electron microscopy and by autoradiography after continuous infusion of tritiated thymidine. The relative amount of viable tissue was assessed with a computer image-analysing program. Graft function was judged by measuring human iPTH in mouse serum.Over 90% of the transplants took and the original structure of the tissue was well preserved. Confluent areas of parathyroid tissue could be seen in 80% of the transplants. The mean loss of viable tissue in all three groups was 45%.Immunohistochemical examination showed ingrowth of vessels from the host into the transplant. The sprouts matured gradually into vessels with thin endothelial linings and capillary fenestrations in adenomatous and hyperplastic transplants but not in transplants of normal tissue.In normal parathyroid tissue the proliferation of parathyroid parenchyma! cells increased only slightly in contrast to the advancing proliferative capacity in adenomatous tissue. In contrast to adenomas, parenchyma! cell proliferative capacity in hyperplastic tissue decreased at 12 week.Concentrations of iPTH were raised at one week in hyperplastic and adenomatous tissue. Twelve weeks after transplantation iPTH concentrations in relation to the amount of transplanted tissue and relative area of viable tissue were comparable in all three groups of transplanted tissue.We conclude that, LDF is a feasible method to study physiological blood flow in human parathyroid glands. Parathyroid blood supply is not as dependent on the inferior thyroid artery as was previously suggested. LDF showed that blood flow recovered in parathyroid glands dissected for in situ preservation and any decision about autografting should be delayed until the end of the operation. Parathyroid transplants re vascularise from host vessels and this is more pronounced and proceeds faster in hyperplastic and adenomatous tissue than in normal transplants. In contrast to nonnal and hyperplastic transplants, adenomatous tissue has a greater and increasing proliferative capacity. The iPTH concentration as an expression of parathyroid function correlates poorly with parenchyma! cell proliferation.
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| 74. |
- Andersen, Pia, 1958-
(författare)
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Physical activity on prescription with access to counsellor support implemented in routine care : Healthcare and patient perspectives
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The Swedish PAP (physical activity on prescription) programme FaR®, introduced in 2001, has been adopted by all Swedish regions, which are responsible for provision of healthcare in Sweden. Several studies have shown positive outcomes of the Swedish PAP on patients’ physical activity and other health-related outcomes. There are no guidelines for best practises of the Swedish PAP, which has led to the development of different organizational structures for its delivery. This thesis project was developed with the ambition of providing knowledge for further development of PAP in clinical practise.Aim: The overall aim was to investigate and generate improved understanding of a structure for physical activity on prescription with access to physical activity counsellors, implemented in routine healthcare.Methods: To address the overall aim, four real-world studies with different design and analysis methods were carried out. The study population consisted of patients 18 years or older prescribed PAP in primary and secondary care in Region Kronoberg’s healthcare organization. Study I investigated characteristics of healthcare delivery of PAP over a four-year period, including all patients prescribed PAP in these years. Study II explored factors that influenced patient’s long-term engagement in physical activity after prescription. Study III investigated differences in physical activity and health-related quality of life (HRQoL) at one-year follow-up between patients who used versus patients who did not use counsellor support after prescription. Study IV investigated factors associated with patients increase in physical activity at one-year follow-up. Data sources for the studies were electronic medical records (Studies I, II, III and IV), individual interviews (Study II) and a baseline and a follow-up questionnaire (Studies III and IV). Different statistical analyses were performed in Studies I, III and IV. Study II used qualitative content analysis based on an approach including both inductive and deductive analysis. The final study samples of PAP recipients were N = 4,879 (Study I), n = 13 (Study II), n = 400 (Study = III) and n = 355 (Study IV).Results: Study I: 4,879 PAP recipients were identified, one-third had used the offer of counsellor support. PAP recipients had a high frequency of diagnosis and healthcare consumption prior to PAP. Counsellor users had higher frequency of multiple diagnoses and healthcare visits than non-counsellor users. The main prescriber of PAP was physicians and the main prescribing setting was primary care. Study II: PAP recipients’ long-term engagement with physical activity was influenced by the determinants of capability, opportunity, and motivation. Receiving a prescription of physical activity, and professional counselling and follow up from a physical activity counsellor, and adaption of PAP to the individual’s capacity were important for patients change of physical activity. Study III: Counsellor users had better outcomes in both physical activity and HRQoL than non-users of this support. Study IV: Nearly half of the PAP recipients had increased physical activity one year after prescription. Increased physical activity was positively associated with lower baseline activity, counsellor use, and positive perception of given support after PAP.Conclusions: Patients who were prescribed PAP had a high frequency of diagnoses and high healthcare consumption in the year prior to the prescription. Due to the positive findings regarding patient outcomes on physical activity, and patient experiences of counsellor support, it could be suggested that individualized counselling and follow up by a physical activity counsellor is of importance for patients’ engagement in physical activity, especially for patients with lower baseline activity. Since increased activity was also seen among nonusers of counsellor support, a general recommendation for physical activity counsellor support for all PAP recipients could not be suggested.
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| 75. |
- Anderson, Emma S., 1975-
(författare)
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The type IV Oligodendrocyte : experimental studies on chicken white matter
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In mammals, islet amyloid polypeptide (IAPP) is co-produced with insulin in pancreatic ß-cells. In the chicken, the expression of IAPP in the brain is more than 10-fold higher than in the pancreas. We made the fortuitous finding that a polyclonal rabbit antiserum raised against chicken IAPP did not recognise the immunogen, but labelled a subpopulation of oligodendroglia! cells in chicken white matter. The hitherto unknown antigen was called T4-O (Type 4 Oligodendrocyte) since it was localised to the Schwann cell-like Type IV oligodendrocyte of Del Rio-Hortega (1928). This formed a starting point for the present thesis, which is centred on the Type IV oligodendrocyte in chicken white matter.Biochemical analysis of chicken spinal cord showed that the T4-O molecule is a protein with a molecular weight of approximately 100 kDa and an isoelectric point of about 4. Further characterisation has not yet been possible.Immunohistochemical studies on frozen sections revealed that the white matter oligodendrocytes exhibit subpopulations expressing T4-O immunoreactivity strongly, weakly or not at all. Strongly T4-O immunoreactive (IR) oligodendrocytes are co-localised with thick myelinated fibres in the ventral (VF) and lateral funiculi of the spinal cord. A corresponding T4-O immunoreactivity is not found in the fish, the frog, the turtle, the rat and the rabbit.To find out when the T4-0 antigen first appears during development we examined sections from embryonic and post-hatching chicken spinal cords by immunohistochemistry. This showed that the T4-O molecule is first expressed in the VF at embryonic day (E)15, after which the number of IR cells increases with age. Oligodendrocytes cultivated in vitro without or with neurons do not develop a T4-O IR phenotype.These findings called for a closer analysis of the structural development of chicken VF white matter. Electron microscopic (EM) examination revealed a developmental sequence of events principally similar to the development of mammalian white matter, but with a more rapid time course. As seen in the electron microscope the first compact myelin has appeared by E12, when most oligodendrocytes are multipolar. By E15 it seems that these cells have developed a Type IV phenotype, possibly by eliminating some sheaths.Histochemical analysis of Vibratome sections showed that Marchi-positive myelinoid bodies are enriched in white matter areas containing many T4-O IR oligodendrocytes and many large myelinated axons.Examination of the three-dimensional (3D) anatomy of early VF oligodendrocytes in Vibratome slices after 04 labelling or after intracellular injection of a fluorescent dye revealed that these units indeed are Schwann cell-like, with a start length of around 50 µm. We also found that these sheaths expand very rapidly, reaching lengths exceeding 200 µm in three days (E12- E15). The 3D data conformed to our EM evidence that the early oligodendrocytes develop a unipolar Schwann cell-like Type IV anatomy through elimination of some sheaths.To my knowledge the present observations represent the first evidence for an oligodendroglia! heterogeneity in the chicken spinal cord. Differences among oligodendrocytes might, conceivably, explain why inherited disorders of myelin metabolism such as Krabbe's disease, affect some CNS areas more than others.
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| 76. |
- Andersson, A. Christer
(författare)
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Acute anterior cruciate ligament injuries : evaluation of surgical och non-surgical treatment
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study comprising 6 separate papers is concerned with the treatment of patients with acute anterior cruciate ligament (ACL) injury. The aim was to compare primary surgical and non-surgical ACL treatment. Treatment was, therefore, instituted at random in all consecutive patients (n = 293) with ACL injury.Initially all patients were investigated by arthroscopy and examined under anesthesia.After 4 years patients treated by ACL repair with combined intraarticular and extraarticular augmentation had a better stability, fewer knee symptoms and a higher level of activity than patients treated by nonaugmented ACL repair or by repair of the associated injuries alone. The patients in the latter group commonly developed instability symptoms and ACL reconstruction was required in 20"7o ofthem. Also they frequently had subsequent meniscal injuries, and an impaired knee function at one-leg-hop tests for distance. Running tests, however, was not correlated to ACL treatment.Another group of patients with acute ACL injury did not have any primary ligamentous repair. At one year 200Jo of the patients needed reconstructive surgery. Moreover, anteriorposterior laxity at one year was increased compared to the initial measurements. The greatest initial laxity was found in patients with an associated tear of the medial collateral ligament (MCL). The patients with combined ACL and MCL injuries had the worst prognosis.In patients with combined injuries who had primary repair of grade 2-3 MCL tears the outcome was similar as for patients with isolated ACL lesion.A simple device for static measurements of anterior-posterior knee displacement was valuable for evaluating the results of ACL treatment. lt can also be used as an aid in the diagnosis of acute knee injury.
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| 77. |
- Andersson, Anna-Maria, 1990-
(författare)
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Mycobacterium tuberculosis and HIV coinfection : Effects on innate immunity and strategies to boost the immune response
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tuberculosis (TB) still remains a big threat today, being the leading cause of death by a single infectious agent. The TB epidemic is fueled by HIV along with the increasing drug-resistance which prolongs the already long treatment duration and decreases the success rate for curing TB. In most cases an infection results in latency but HIV patients have a 20-30 times higher risk of developing active TB. There are around 36.9 million people living with HIV globally, with the highest burden in Africa. Although there are effective treatments against the disease, there is no cure for AIDS and the availability of the lifelong treatment is limited in low-income countries were the burden is highest. HIV infection causes an immunodeficiency characterized by the progressive loss of CD4 T cells which increases the risk of opportunistic infections, and infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB. Mtb spreads through aerosols from one person with active tuberculosis to a healthy person. Upon inhalation the bacteria are phagocytosed by alveolar macrophages that secrete cytokines and chemokines to recruit more cells, such as dendritic cells, macrophages and lymphocytes, leading to the formation of a granuloma. During a single TB infection the bacteria are usually contained within the granuloma, but HIV can disrupt the stable granuloma, causing a rupture and dissemination of Mtb. This inflammatory site is also beneficial to HIV since it promotes replication of the virus within infected cells. HIV and Mtb are two successful intracellular pathogens able to avoid immune defense mechanisms both of the innate and adaptive immunity in order to persist and replicate. Their virulence factors can manipulate or inhibit cell signaling, phagosome maturation, autophagy, ROS production, apoptosis and antigen presentation, to promote survival. Boosting of immune defenses with host-directed therapies (HDT) has been proposed as a treatment strategy against TB, either alone or adjunctive to the current regimen.In this thesis, ways to boost the innate immune responses in Mtb and HIV coinfected macrophages were investigated, along with studies of the effect of HIV on Mtb antigen presentation in coinfected dendritic cells. The initial hypothesis was that autophagy induction through inhibition of mammalian target of rapamycin (mTOR) could suppress Mtb growth in HIV coinfected macrophages. However, during a low grade infection, autophagy induction increased Mtb replication due to a decreased autophagic flux and acidification of Mtb phagosomes. A general autophagic flux was induced, although not localized to the Mtb phagosomes, thus not inducing a xenophagy (autophagy of intracellular pathogens). Other ways of inducing autophagy or boosting the response in coinfected macrophages might be more beneficial and therefore the effect of efferocytosis was investigated. Uptake of apoptotic neutrophils by coinfected macrophages did not induce autophagy but enhanced the control of Mtb by other means. Upon efferocytosis, the macrophages acquired active myeloperoxidase (MPO) from the neutrophils that suppressed Mtb growth. The coinfected macrophages also produced more ROS after efferocytosis. The inhibition of Mtb growth could thus be mediated by MPO and the increased ROS production either directly or indirectly.The possibility to boost the innate immunity could prove to be important during an HIV coinfection, when the adaptive immunity is deficient. In addition to the well-known decline in CD4 T cells during the course of HIV progression, we found that HIV infection of dendritic cells inhibited antigen presentation by suppressing the expression of HLA-DR and co-stimulatory molecules on coinfected dendritic cells. Furthermore, HIV reduced secretion of pro-inflammatory cytokines and suppressed antigen processing through inhibition of autophagy. This impaired antigen presentation in coinfected dendritic cells resulted in a decreased activation and response of Mtb-specific CD4 T cells.In conclusion, this thesis shows how HIV can manipulate antigen presentation in Mtb coinfected dendritic cells and subsequently inhibit the adaptive immune response. It also contributes to insights on how efferocytosis of apoptotic neutrophils can boost the innate immune responses during coinfection. Lastly, autophagy induction through mTOR inhibition does not enhance protection against TB. Induction of autophagy should therefore be handled with care, particularly during HIV coinfection.
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| 78. |
- Andersson, Bengt-Åke
(författare)
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Circulating Biomarkers in Patients with Head and Neck Cancer and the Influence of Cigarette Smoking
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Head and neck cancer (HNC) is a collective name for heterogeneous tumors located in the head and neck regions for which smoking, alcohol and human papillomavirus (HPV) are documented risk factors. The survival of HNC patients has only improved marginally during the last decade. The most important prognostic factors are tumor size, local spread and distant metastases, tumor node metastasis (TNM) staging. Prognostic biomarkers are needed as a complement to TNM staging.The aim for this thesis was to investigate rapid and low cost blood based biomarkers which could indicate the risk of HNC, recurrence of the disease or the survival of HNC patients. Furthermore, the aim was to examine how cigarette smoking influences the levels of biomarkers.In paper I, a possible role of plasma cytokines or proteins associated with immune response or inflammation, as biomarkers for the survival of HNC patients was investigated. Higher levels of C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-α) were detected in plasma of the patients compared with the levels in the controls. The elevated levels of these two biomarkers detected in patients were associated with decreased survival.In paper II, the influence of 45 single nucleotide polymorphisms (SNPs) located in 41 genes associated with cell cycle progression, cell death, DNA repair or immune response on cancer risk, tumor recurrence and survival in HNC patients were investigated. SNPs in immune response genes were associated with risk for HNC, an elevated risk for recurrence and a decreased survival in HNC patients.In paper III, the influence of cigarette smoking on levels of inflammatory cells, proteins or cytokines/chemokines, microRNAs (miRNAs) and SNPs was analysed in healthy smokers and non-smokers. Higher levels of total white blood cells (WBCs), neutrophils, monocytes, lymphocytes, neutrophil to lymphocyte ratio (NLR), CRP, monocyte chemoattractant protein- 1 (MCP-1) and interferon gamma (IFN-γ) were detected in smokers compared to non-smokers and indicate an inflammatory response. Also, a lower level of oncomiRNA miR-21was detected in smokers. This alteration, in combination with the elevated levels of IFN-γ in smokers could be a protective response to cigarette smoke. The higher levels of IFN-γ in smokers compared to non-smokers were however only detected in individuals with SNP rs2069705 genotype AG/GG. This indicates a genetic association of the levels of IFN-γ.In paper IV, the separate effects of cigarette smoking and HNC on inflammatory or immune biomarkers and the impact of high risk human papillomavirus, age and gender were investigated. Comparisons of circulating levels of WBCs and its subpopulations, plasma proteins or cytokines/chemokines between smoking and non-smoking patients, smoking and non-smoking controls and between the patient and control groups were analysed. Smoking had highest impact on elevated levels of WBCs, IFN-γ and MCP-1, and HNC had highest impact on elevated levels of neutrophils, monocytes, NLR, CRP, macrophage inflammatory protein 1 beta and TNF-α.In conclusion, host immune response associated parameters could be suitable as biomarkers for the risk of HNC, risk of recurrence or in predicting survival of HNC patients. This thesis show that HNC are associated with systemic inflammatory response and upregulated CRP and TNF-α is related to shorter survival in HNC patients. Additionally, SNPs in immune response genes such as rs1800629 in the TNF-α gene indicates a risk for HNC or an elevated risk for recurrence and a decreased survival in HNC patients. These rapid and low cost blood based biomarkers could be used in combination or as a supplement to established biomarkers in the clinic for a more personalized treatment modality.
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| 79. |
- Andersson, Eva, 1946-
(författare)
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Vitamin A and ß-carotene metabolism and effects of UV irradiation in human keratinocytes and melanocytes
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Retinoids (vitamin A and its derivatives) are modulators of proliferation and differentiation. Both retinol (ROH) and its metabolite 3,4-didehydroretinol (ddROH) can be converted to retinoic acid (RA) and 3,4-didehydroretinoic acid (ddRA), ligands for the nuclear receptors, which induce gene transcriptions. A perturbed ROH metabolism is observed in several dermatoses and iu non-melanoma skin cancer. Dietary ß-carotene has been considered to play a critical role in the natural defence against cancer. Whether ß-carotene is converted to ROH in the skin has been debated.We have investigated ß-carotene and retinoid metabolism, retinoid binding proteins and retinoid receptors in human keratinocytes (KCs) and melanocytes (MCs) in vitro. Similar studies of vitamin A have been done in human malignant epithelial cells (HeLa) and malignant melanoma cells. The influence of ultraviolet radiation (UVR) on retinoid metabolism and receptor expression was specially focused upon this thesis. KCs and MCs contained high concentrations of ROH, ddROH, while HeLa- and melanoma cells contained lower levels. KCs contained the highest level of the retinoid-binding proteins CRBP I and CRABP II compared to MCs, HeLa and melanoma cells. High CRABP II levels showed a correlation with the ability to accumulate ddROH. In MCs, CRABP I was highly expressed, but in melanoma cells CRABP II dominated. The difference between MCs and melanoma cells in receptor levels was most pronounced for RARß, which was highly expressed in melanoma cells. Such dissimilarities between benign and malignant MCs might play a role in differentiation and growth regulation. The uptake of [3H]ROH, [3H]RA and ß-carotene was significantly higher in MCs than in KCs. We were able to demonstrate that [14C]ß-carotene was converted to [14C]ROH in both these cell types. This suggests that this local storage of ß-carotene might serve as au alternative supply for vitamin A in the skin.A moderate dose of UVR reduced the concentration of ROH, ddROH and [3H]RA in KCs and MCs by 20-50%. The concentration returned to starting levels in 1-2 days, and could be explained by a retarded metabolism of RA, the biologically most active metabolite. When KCs and MCs were exposed to UVR, the mRNA and protein levels of the three nuclear retinoid receptors (RARα, RARγ and RXRα) decreased rapidly. In MCs these levels were close to normal 3 days postirradiation. In KCs only the RARα mRNA and protein levels returned to baseline within 3 days. This thesis has increased our knowledge of the effects of UVR on retinoid metabolism and retinoid receptors in human cells. Further studies are needed to understand the role of ß-carotene and retinoid signaling in UV induced skin cancer.
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| 80. |
- Andersson, Inger S
(författare)
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Utveckling av metoder för mätning av vårdkvalitet : Med inriktning mot omvårdnad
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present thesis has its roots in the need to measure and evaluate quality of care, especially in times when resources allocated to health- and medical care are being limited. This is of concern for many groups in society, but perhaps mOst of all for patients, hospital staff and politicians.The main purpose of the thesis was to develop methods for measuring quality of care within nursing.The thesis has been organised in three main parts, the first of which deals with the principal concepts in this research,in addition to research and develop- ment in existing instruments for measuring quality of care. The second part contains the empirical study and its results. Finally, the third part deals with the development of variables for methods of measurement based on the empirical study: it also looks ahead, at visions and viewpoints governing future research and development work.Data collection was carried out by means of a thematic interview, and by measuring attitudes to quality of care on a modified attitude scale based on Osgood's semantic differential. The interview group comprised 128 people; 25 patients and 25 staff members at a local hospital, 25 patients and 27 staff members at a health centre, and 26 county council politicians. The interview material was analysed inductively using qualitative and quantitative content analysis. On analysing the three themes which dealt with the interviewees' perception of health, quality of life as a result of care received, the quality of selfcare as well as care goals, literature studies were added which dealt with the above-mentioned phenomena.The result of the interview study, and the literature studies included in the analysis phase, can be stated in brief, that the main focus in the perception of quality of care held by the patients, the staff and the politicians was on 1) the quality of the staff, with an emphasis on the characteristics and skills of the staff, 2) quality in implementing care, involving care measures of an affective nature and the quality of the patient- staff relationship, and 3) the patient-related quality of results, consisting of such changes in the patient's health status as a cure or a change in health; cognitively oriented results like better knowledge about one's condition; wellbeing as a result of care; satisfaction with the care and treatment provided, and with the staff.The result of the attitudes survey was that politicians were the most positive towards the quality of the care provided, while the personal at the health centre were the least positive. Of the various professional categories interviewed, physicians were the most positive. Other staff comprising paramedical groups were the least positive.Further groups of variables have been generated from the data collected and from the literature studies in order to extend the evaluation of the quality of nursing care. All of the variable groups developed in the present thesis have been named and grouped together in a system called the KISAAL system, after the initials of the author. The different groups of variables can be related to each other to facilitate a total assessment of the quality of nursing care, and its management.
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