| 51. |
- Andersson, Ulrika, 1963-
(författare)
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Experimental studies in brain tumours : with special regard to multidrug resistance and the ErbB-family
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Primary brain tumours, and especially the most common form malignant gliomas, usually display a pronounced resistance to other treatment modalities when surgery fails to cure. Growth factors, such as EGF and its receptor, frequently amplified and overexpressed in malignant gliomas, and factors associated with multidrug resistance have been suggested to at least partially explain the poor outcome. The aim of this thesis was to characterise factors in primary brain tumours associated with the development of resistance with focus on the epidermal growth factor receptor (ErbB) family, and multidrug resistance (MDR). Influences of irradiation on the expression and activity of P-glycoprotein (Pgp) in malignant gliomas was evaluated. The effects showed that irradiation increased the efflux activity of Pgp in rat brain vascular endothelial cells, but not in glioma cells. In the intracranial BT4C glioma model, Pgp was detected in the capillary endothelium in the tumour tissue but not in glioma cells. Expression of several factors coupled to MDR (Pgp, MRP1, LRP, and MGMT) in primary brain tumours were analysed and correlated to clinical data. In gliomas, Pgp and MRP1 were predominantly observed in capillary endothelium and in scattered tumour cells, whereas LRP occurred only in tumour cells. In meningiomas, expression of the analysed markers was demonstrated in the capillary endothelium, with a higher expression of Pgp and MRP1 in transitional compared to meningothelial meningiomas. A pronounced expression of MGMT was found independently of the histopathological grade or tumour type. Survival analysis indicated a shorter overall survival for patients suffering from low-grade gliomas with high expression of Pgp. To explore the importance of the epidermal growth factor receptor (EGFR), expression levels of the family members (EGFR, ErbB2-4) were analysed and their relations to various clinical parameters were evaluated in gliomas and meningiomas. In gliomas, the highest EGFR expression was observed in high-grade tumours, while ErbB4 expression was most pronounced in low-grade tumours. In meningiomas, expression of EGFR, ErbB2, and ErbB4 was observed in the majority of the tumours. An intriguing observation in low-grade gliomas was a significantly decreased overall survival for patients with high EGFR protein expression. The effects of different time schedules for administration of the selective EGFR inhibitor ZD1839 in relation to irradiation of glioma cells were analysed. The analyses showed a heterogeneity in the cytotoxic effects of ZD1839 between cell lines, and it was obvious that some of the cell lines showed sensitivity to ZD1839 despite no or low expression of EGFR. The study also demonstrated the importance of timing of ZD1839 administration when this agent is combined with irradiation. In conclusion, in order to enhance the efficacy of radiotherapy by various drugs in malignant gliomas it may be essential to inhibit drug efflux activity in endothelial cells and to deliver drugs in an optimal timing in relation to radiotherapy. The heterogeneity in expression of drug resistance markers, as well as the ErbB family reflects the complexity in classification of primary brain tumours, and indicates that subgroups of patients with low-grade gliomas expressing Pgp and EGFR might benefit from more aggressive and individualised treatment.
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| 52. |
- Andréen, Lotta, 1961-
(författare)
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Allopregnanolone and mood : studies of postmenopausal women during treatment with progesterone
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction. Allopregnanolone and pregnanolone (neuroactive metabolites of progesterone) act as positive modulators of the GABAA receptor system which is the major inhibitory system in CNS. Contradictory results on the effect of GABAA receptor modulators are reported. Beneficial properties such as anaesthesia, sedation, and anxiolysis are reported as well as adverse, anxiogenic and aggressive effects. It has been suggested that GABAA receptor agonists have bimodal effects. Low concentrations increase an adverse, anxiogenic effect, whereas higher concentrations show beneficial, calming properties. Aims. To investigate if progesterone treatment induces adverse mood in postmenopausal women and if the severity in mood symptoms is related to progesterone, allopregnanolone or pregnanolone serum concentrations. To evaluate differences in steroid concentrations induced by different doses and routes of administration of progesterone. Methods. Two randomised, placebo-controlled, double-blind crossover studies of postmenopausal women were performed. Subjects were treated with estradiol continuously. Different doses of progesterone, given vaginally or orally, were added sequentially during the last 14 days of each treatment cycle. Daily symptom ratings were kept using a validated rating scale. Blood samples for progesterone, allopregnanolone and pregnanolone analyses were collected during each treatment cycle. A study regarding the pharmacokinetics after ingestion of low-dose oral progesterone was conducted with postmenopausal women. Blood samples for the analyses of progesterone, allopregnanolone and pregnanolone were collected and pharmacokinetic parameters were calculated. Results. Certain postmenopausal women on sequential HT with vaginal and oral progesterone experience mood deterioration during the progesterone phase while on a low dose of progesterone but not on higher doses or the placebo. Negative mood symptoms occurred when the serum concentration of allopregnanolone was similar to endogenous luteal phase levels, whereas lower and higher concentrations had no effect on mood. Pharmacokinetic analyses show that low-dose oral progesterone can be used as a prodrug to allopregnanolone when the aim is to achieve physiological concentrations of allopregnanolone. Conclusions. A bimodal association between allopregnanolone concentration and adverse mood is observed in postmenopausal women treated with progesterone. The addition of low-dose progesterone to estradiol induces adverse mood in postmenopausal women, whereas higher doses and placebo have no mood-deteriorating effect.
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| 53. |
- Anticona Huaynate, Cynthia, 1983-
(författare)
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Lead exposure in indigenous children of the Peruvian Amazon : seeking the hidden source,venturing into participatory research
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction. In 2006, a Peruvian environmental agency reported the presence of elevated blood lead levels (BLLs) in indigenous communities of the Corrientes river basin. This is a territory in the Peruvian Amazon where oil activity has been associated with serious environmental effects, with impact on an ongoing social conflict. This PhD project aimed to determine the lead sources, risk factors and pathways in children of these communities and to suggest control and prevention strategies. Given the arguments attributing the lead source to the oil activity pollution, the second objective was to clarify any potential connection between the two. This project was conducted by a collaborative research partnership with the regional health authorities and the community-based organization. The third objective was to characterize the challenges, facilitating factors and the lessons learned from the research process.Methods. Two epidemiological studies were conducted. Study I (2009) was carried out in three communities and study II (2010) in six communities with different levels of exposure to oil activity. The participants were children 0–17 years old. Data collection included: determination of BLLs, hemoglobin levels and anthropometric indicators, a risk factor questionnaire, an environmental assessment and a risk map. Data analysis included univariate, bivariate and multivariate logistic regression. Data for the third objective came from field notes, documents, interviews and a process of collective reflection.Results. Study I (n= 221) found no significant difference in the geometric mean(GM) BLLs between the communities exposed and not exposed to oil activity. Older age and being a boy were found as risk factors for BLLs ≥ 10 μg/dL. In study II (n= 346), age stratified logistic regression models indicated that children 0–3 years whose mothers had BLLs ≥ 10 μg/dL, children 0–6 years who played with pieces of lead and children 7–17 years who fished 3 times or more per weekor chewed pieces of lead to manufacture fishing sinkers had a significant increased risk of having BLLs ≥ 10 μg/dL. Children who lived in communities near oil battery facilities also had a significant increased risk of having BLLs ≥ 10 μg/dL. In both studies, environmental samples showed lead concentrations below reference levels. The challenges and facilitating factors identified focused on five interrelated themes: i) mutual trust, ii) multiple agendas, iii) equal participation, iv) competing research paradigms and v) complex and unexpected findings.Conclusions. Metal lead appeared to be the main source of exposure. Playing with pieces of lead and chewing pieces of lead to construct fishing sinkers appeared to be pathways of exposure for children aged 0–6 years and 7–17 years, respectively. Mothers’ BLLs > 10 μg/dL was a risk factor for BLLs > 10 μg/dL in children aged 0–3 years. Living in a community with high exposure to oil activity was a risk factor for BLLs > 10 μg/dL. The identified connection with oil activity was the proximity of communities to oil battery facilities and thus greater access to lead from cables and other industrial waste. Despite the numerous challenges, participatory research appears to be the most appropriate approach for this type of context. The study findings led us to recommend:i) a comprehensive community-based lead control and prevention plan,ii) the introduction of substitute non-harmful material(s) for fishing sinkers and iii) secure containment of the oil company’s waste deposits.
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| 54. |
- Antonsson, Helena, 1962-
(författare)
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Interaktion i särskilt boende för personer med utvecklingsstörning och utmanande beteende
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bakgrund: Många personer med utvecklingsstörning har kommunikativa svårigheter och har därför behov av att utveckla olika sätt att kommunicera för att kunna förstå andra och göra sig förstådda. Svårigheter i kommunikationen påverkar interaktionen mellan personer med utvecklingsstörning och deras vårdare. Detta ställer höga krav på vårdare att kunna tolka och förstå den enskilda individens sätt att uttrycka önskningar och behov. På samma sätt riskerar vårdares budskap att missförstås. Om vårdaren misslyckas att förstå den boendes kommunikation och vice versa, kan det leda till situationer med utmanande beteende exempelvis i form av vägran, verbal eller fysisk aggressivitet.Syfte: Det övergripande syftet med avhandlingen är att studera interaktion mellan vuxna personer med utvecklingsstörning och vårdare i gruppbostäder, samt att studera effekter av en utbildningsintervention för vårdare som arbetar i gruppbostäder.Metod: Avhandlingens samtliga delstudier har genomförts i gruppbostäder för personer med utvecklingsstörning bland boende och vårdare i ett län i norra Sverige. I studie I insamlades data kring 556 personer med utvecklingsstörning. I studie II och III deltog 16 vårdare och 11 personer med utvecklingsstörning. I studie IV deltog 7 vårdare. Studie I bygger på personalens skattningar av funktionsnivåer och förekomst av begränsningsåtgärder. I Studie II och III utgörs data av videoobservationer och narrativa intervjuer. I studie IV användes flera datainsamlingsmetoder i en mixed method design med både vårdarnas skattningar, med hjälp av instrument och semi-strukturerade intervjuer. Analys av materialet i studie II, III och IV har gjorts med kvalitativ innehållsanalys och i studie I och IV har data analyserats statistiskt.Resultat: I studie I framkom att av 556 boende hade 99 (18%) varit föremål för fysiska begränsningsåtgärder under den senaste veckan. Av dessa 99 hade nästan alla varit föremål för mer än en typ av begränsningsåtgärd. Den vanligaste begränsningsåtgärden var bälte i stol (74%). Användningen av begränsningsåtgärder var relaterade både till fysiska funktionsnedsättningar och till beteende.I studie II reflekterade vårdare över videoinspelad interaktion där vårdarna medverkat, både framgångsrik och misslyckad interaktion. Exempel på framgångsrik interaktion var att förstå tecken, kunna möta behov och hantera situationer med utmanande beteenden. Vårdarna reflekterade över att framgångsrik interaktion ledde till säkerhet, trygghet och självförtroende hos de boende. Vårdarna reflekterade även över de konsekvenser misslyckad interaktion fick i form av irritation, aggression och våld från de boende.I studie III studerades videoinspelad interaktion mellan 11 personer med utvecklingsstörning och 16 av deras vårdare. Verbal och icke-verbal interaktion identifierades. Fyra inspelade situationer valdes ut för att belysa framgångsrikt samspel. Resultatet visade att framgångsrikt samspel mellan personer med utvecklingsstörning och deras vårdare bland annat bygger på möjligheten att bekräfta varandra, dela vardagshändelser, ge tid och utrymme och på att använda ett kongruent och tydligt språk.I studie IV utvärderades effekterna av en web-baserad utbildningsintervention, vars syfte var att förbättra interaktionen mellan personer med utvecklingsstörning och vårdare samt att därmed reducera förekomsten av situationer med utmanande beteende. Resultatet visade att vårdarna hade förbättrat sin förmåga att hantera situationer med utmanande beteende och att förekomsten av utmanande beteende minskat. Vårdarna beskrev att den web-baserade utbildningen upplevts givande och möjlig att ta del av parallellt med arbetet.Slutsats: Fysiska begränsningsåtgärder förekommer i gruppbostäder för personer med utvecklingsstörning. Användningen av begränsningsåtgärder kan vara relaterade både till fysiska funktionsnedsättningar och till beteenden i samspelet mellan brukare och vårdare. Vårdare upplever användningen av fysiska begränsningsåtgärder svår och tröttande. Brott i kommunikationen mellan personer med utvecklingsstörning och deras vårdare kan leda till försvårad interaktion med risk för situationer med utmanande beteenden. När vårdare är framgångsrika i interaktionen med personer med utvecklingsstörning ger det tillfredsställelse både för de boende och vårdarna. Vårdarna upplever dock ofta hjälplöshet och osäkerhet i relation till hantering av situationer med utmanande beteende och efterfrågar utbildning. Web-baserad utbildning om interaktion med personer med utvecklingsstörning och utmanande beteende har i vår studie visat sig ge lovande effekter och bör vara möjlig att utveckla för både introduktion av nyanställda vårdare och för kompetensutveckling bland mer erfaren personal.
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| 55. |
- Appelblad, Micael, 1961-
(författare)
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Fat contamination of pericardial suction blood in cardiac surgery : clinical and experimental studies in perspectives of transfusion logistics
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: During cardiac surgery aided by cardiopulmonary bypass (CPB) the autotransfusion of pericardial suction blood (PSB) is regarded mandatory to limit allogeneic blood exposure. PSB is however proposed as a source of lipid microemboli and to contribute to brain damage. This thesis addresses the logistics of allogeneic blood transfusion during coronary artery bypass grafting (CABG), the embolic potential of reinfused PSB, and means to reduce PSB fat contamination, investigated both clinically and experimentally. Methods: Study I) Patients undergoing CABG surgery (n=2469) were included in a database study. The magnitude of surgical bleeding versus blood transfusion was analyzed to extract a subgroup of patients (n=982) in whom transfusions were independent from bleeding. Study II) PSB and venous-blood samples were collected from patients undergoing routine CABG (n=20). The in vitro capillary-flow properties of blood subcomponents and the effects of routine screen filtration were tested. PSB fat contamination was evaluated by imprint microscopy. Study III) Heat extracted liquid human fat or soya oil were mixed with mediastinal drain blood (n=20) and incubated in a temperature controlled column, to evaluate spontaneous density separation of fat. Study IV) The findings from study-III were applied to develop a fat-reducing system (FRS) using two stacked compartments. The FRS was experimentally tested (n=12), with similar methods as in study-III, and clinically evaluated (n=10). A single-chamber blood bag (n=10) served as reference. Results: Study I) A surgical bleeding of less than 400 mL showed no correlation to blood transfusion, although 64 of 982 patients still received allogeneic blood. The strongest predictors for this kind of transfusion were; female gender, weight ≤70 kg, CPB time ≥90 minutes, CPB temperature ≤32 ºC, and advanced age (P<.001 - .038). Study II) The capillary-flow profile of PSB plasma was highly impaired compared to venous plasma (P<.001). Conversely, blood-cell components showed no difference between PSB and venous blood. Routine screen filtration showed no ameliorating effect on capillary-flow resistance. Fat debris was detected on imprints in all PSB samples in contrast to venous plasma (P<.05). Study III) After 10-min of incubation had 77% of added soya oil separated and found contained in the top 20% fraction of blood (P<.001), aimed to be discarded. The density separation of human fat was less efficient compared to soya oil (P=.011). Fat also adsorbed to surface which was more pronounced at low temperature (P<.001). The overall reduction of human fat was 70%. Study IV) PSB contained 1.5 mL fat suspended in 418 mL PSB. Of this fat was 24% surface-bound. Experimental analysis of the proposed FRS revealed an 83% fat-reduction which was clinically confirmed, suggesting 80% reduction (P=.001). The FRS also gave a small but significant erythrocyte-concentrating effect. Conclusions: Transfusion of allogeneic blood during CABG surgery appeared associated with an institutional, individual, and technical bias of an anticipated need and not only used to compensation for surgical bleeding. In part may this reflect a non-compliant CPB methodology and hemodilution. It was confirmed that PSB plasma contained fat, with a suggested embolic potential. Human fat was significantly reduced from mediastinal drain blood by spontaneous density separation and surface adsorption. The prototype FRS used for PSB incubation during CPB allowed an efficient fat reduction.
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| 56. |
- Araya, Mesfin, 1954-
(författare)
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Postconflict internally displaced persons in Ethiopia : mental distress and quality of life in relation to traumatic life events, coping strategy, social support, and living conditions
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: There are about 23.7 million internally displaced persons worldwide today, still living in the low-income countries. Ethiopia has for the past four decades been ravaged by war and famine. A lengthy civil war resulted in Eritrea, formerly a part of Ethiopia, becoming an independent state in 1991. This war led to displacement of one million people, and currently there are about 55000 internally displaced Ethiopians in Addis Ababa, most of them living in temporary shelters. A minority resettled in a small town Debre Zeit south east of Addis Ababa, dispersed in the community. Objectives: To study the consequences of trauma and extreme stress among these displaced persons. Methods: A random sample of 1200 displaced persons was selected from the Kaliti and Kore shelters of Addis Ababa, aged between 18 and 60 years. They were interviewed by internationally validated instruments which were translated into the Ethiopian official language Amharic. Information thus obtained covered sociodemographics, childhood trauma, traumatic life events, and mental distress as assessed by the SCL-90-R, the four domains of quality of life assessed by WHOQOL-BREF, coping strategies, perceived social support, and basic living conditions. A sample of 120 subjects from the displaced persons living in Debre Zeit was similarly evaluated. A study comparing prevalence rates and risk factors for PTSD in four postconflict, low-income countries (Algeria, Cambodia, Ethiopia, Gaza) was also undertaken. Results: Men, compared to women, reported significantly higher experience of trauma, higher perceived social support, and higher task-oriented coping. Women reported higher emotion-oriented coping. In both genders, emotion-oriented coping was correlated with higher trauma events, and task-oriented coping was correlated with higher perceived social support. Mental distress increased and quality of life decreased with age. Mental distress mediated the effects of most trauma in reducing quality of life, and some trauma reduced quality of life directly. Living conditions were also significantly related to quality of life. Coping strategies and perceived social support influenced mental distress and quality of life directly as well as indirectly by moderation, in part gender specific. Placement in the community setting of Debre Zeit gave a better quality of life compared to placement in the shelters of Addis Ababa. This difference was accounted for by the difference in living conditions, particularly protection from animals (rodents) and insects (mosquitoes), for three domains of quality of life. For domain 3 (social relationships), however, several further factors accounted for the difference, like marital status, ethnic belonging and coping strategy. The comparative study of 4 postconflict countries contributes to the theory that trauma may be the direct cause of the onset of PTSD but that a multiplicity of other adverse events determine the development of this disorder. Conclusions: Using the same assessment methods, a wide range of rates of symptoms of PTSD were found among 4 low-income populations who have experienced war, conflict, or mass violence. In the Ethiopian context we also found gender differences in the trauma background, coping strategies and perceived social support. Mental distress mediated much of the effects of trauma on quality of life. Coping strategies and perceived social support were significant moderators in this process.
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| 57. |
- Árnadóttir, Guðrún, 1955-
(författare)
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Measuring the impact of body functions on occupational performance : validation of the ADL-focused occupation-based neurobehavioral evaluation (A-ONE)
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Among the instruments commonly used by occupational therapists working in the area of rehabilitation of persons with neurological disorders are evaluations of both occupation, such as activities of daily living (ADL), and body functions. While persons with neurological diagnoses typically have symptoms that represent diminished neurobehavioral functions, the resulting pattern of neurobehavioral impairments affecting ADL performance often differs among diagnostic groups. Usually, neurobehavioral impairments are evaluated in a context that is separate from and not natural for ADL task performance. The A-ONE is a unique instrument that can be used to evaluate both ADL performance (ADL scale) and, in the natural context of the ADL task performance, the underlying neurobehaviors that cause diminished ADL task performance among persons with neurological disorders (Neurobehavioral scale). The scales of the instrument are of ordinal type, and in their existing form, do not have measurement properties. Measurement properties are a requirement of evidence-based and quality assured rehabilitation services.The overall aim of this doctoral study was to further develop and validate the A-ONE. This included (a) internal validation to explore the potential for converting the ordinal scales of the instrument to interval scales, (b) examination of which of the neurobehavioral items would be most beneficial and clinically useful for constructing a new Neurobehavioral Impact (NBI) scale for evaluating persons with different neurological diagnoses, and (c) exploration of whether persons with right and left cerebrovascular accidents (RCVA, LCVA) differ in mean NBI measures. Methods: This thesis is comprised of four studies which all contribute in different ways to the validation of the scales of the A-ONE. In the first three studies, Rasch analyses, a widely accepted modern test theory methodology, was used to examine internal validity of the scales and the reliability of the A-ONE measures. In the fourth study, ANCOVA was used to explore between group differences, and Pearson correlation coefficients were used to explore relations between person measures from the different A-ONE scales.Results: The first study of 209 persons diagnosed with CVA and dementia provided support for converting the ordinal ADL scale to an interval scale that has potential to be used to measure change in ADL performance over time. The second and third studies, including 206 and 422 persons respectively, indicated that it is possible to construct several unidimensional versions of a new NBI scale from the neurobehavioral items of the instrument, each with different item content and hierarchical item structure. Further, some of these NBI scales could be used across different diagnostic groups. When exploring differences between 215 persons with RCVA and LCVA on the NBI scale developed for CVA, results of the ANCOVA (with ADL ability as a covariate) indicated that there is no significant difference between groups in their mean NBI measures, despite known differences in patterns of neurobehavioral impairments.Conclusions: The results of this thesis indicate that the A-ONE, although developed by traditional psychometric methods for the purpose of providing useful information for intervention planning, now also has the potential to be used to measure change and compare diagnostic groups. This additional feature will likely enhance both clinical and research potential of the instrument. In order to make the results of the study accessible for clinicians, conversion tables need to be developed.
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| 58. |
- Arnadottir, Solveig, 1968-
(författare)
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Physical activity, participation and self-rated health among older community-dwelling Icelanders : a population-based study
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The main objective of this study was to investigate older people’s physical activity, their participation in various life situations, and their perceptions of their own health. This included an exploration of potential influences of urban versus rural residency on these outcomes, an evaluation of the measurement properties of a balance confidence scale, and an examination of the proposed usefulness of the International Classification of Functioning, Disability and Health (ICF) as a conceptual framework to facilitate analysis and understanding of selected outcomes.Methods: The study design was cross-sectional, population-based, with random selection from the national register of one urban and two rural municipalities in Northern Iceland. There were 186 participants, all community-dwelling, aged 65 to 88 years (mean = 73.8), and 48% of the group were women. The participation rate was 79%. Data was collected in 2004, in face-to-face interviews and through various standardized assessments. The main outcomes were total physical activity; leisure-time, household, and work-related physical activity; participation frequency and perceived participation restrictions; and self-rated health. Other assessments represented aspects of the ICF body functions, activities, environmental factors and personal factors. Moreover, Rasch analysis methods were applied to examine and modify the Activities-specific Balance Confidence (ABC) scale and the ICF used as a conceptual framework throughout the study.Results: The total physical activity score was the same for urban and rural people and the largest proportion of the total physical activity behavior was derived from the household domain. Rural females received the highest scores of all in household physical activity and rural males were more physically active than the others in the work-related domain. However, leisure-time physical activity was more common in urban than rural communities. A physically active lifestyle, urban living, a higher level of cognition, younger age, and fewer depressive symptoms were all associated with more frequent participation. Rural living and depressive symptoms were associated with perceived participation restrictions. Moreover, perceived participation restrictions were associated with not being employed and limitations in advanced lower extremity capacity. Both fewer depressive symptoms and advanced lower extremity capacity also increased the likelihood of better self-rated health, as did capacity in upper extremities, older age, and household physical activity. Rasch rating scale analysis indicated a need to modify the ABC to improve its psychometric properties. The modified ABC was then used to measure balance confidence which, however, was found not to play a major role in explaining participation or self-rated health. Finally, the ICF was useful as a conceptual framework for mapping various components of functioning and health and to facilitate analyses of their relationships.Conclusions: The results highlighted the commonalities and differences in factors associated with participation frequency, perceived participation restrictions, and self-rated health in old age. Some of these factors, such as advanced lower extremity capacity, depressive symptoms, and physical activity pattern should be of particular interest for geriatric physical therapy due to their potential for interventions. While the associations between depressive symptoms, participation, and self-rated health are well known, research is needed on the effects of advanced lower extremity capacity on participation and self-rated health in old age. The environment (urban versus rural) also presented itself as an important contextual variable to be aware of when working with older people’s participation and physically active life-style. Greater emphasis should be placed on using Rasch measurement methods for improving the availability of quality scientific measures to evaluate various aspects of functioning and health among older adults. Finally, a coordinated implementation of a conceptual framework such as ICF may further advance interdisciplinary and international studies on aging, functioning, and health.
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| 59. |
- A'roch, Roman, 1959-
(författare)
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Left ventricular function's relation to load, experimental studies in a porcine model
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Loading conditions are recognized to influence ventricular function according to the Starling relationship for length/stretch and force. Many modern echocardiographic parameters which have been announced as describing ventricular function and contractile status, may be confounded by uncontrolled and unmeasured load. These studies aimed to measure the relation between four different types of assessments of ventricular dysfunction and degrees of load. Study examined the ‘myocardial performance index’ (MPI). Study II examined long axis segmental mechanical dyssynchrony. Study III examined tissue velocities, and Study IV examined ventricular twist. All studies aimed to describe the relation of these parameters both to load and to inotropic changes. Methods: In anesthetized juvenile pigs, left ventricular (LV) pressure and volume were measured continuously and their relationship (LVPVR) was analysed. Preload alterations were brought about by inflation of a balloon tipped catheter in the inferior vena cava (IVCBO). Inotropic interventions were brought about by either an overdose of anesthetic (combine intravenous pentobarbital and inhaled isoflurane, Study I), or beta blocker and calcium channel blocker given in combination (Studies III and IV). In one study (II), global myocardial injury and dysfunction was induced by endotoxin infusion. MPI measurements were derived from LVPVR heart cycle intervals for isovolumic contraction and relaxation as well as ejection time. Long axis segmental dyssynchrony was derived by analyzing for internal flow and time with segmental dyssynchronous segment volume change during systole, hourly before and during 3 hours of endotoxin infusion. Myocardial tissue velocities were measured during IVCBO at control, during positive and then later negative inotropic interventions. The same for apical and base circumferential rotational velocities by speckle tracking. Load markers (including end-diastolic volume) were identified for each beat, and the test parameters were analysed together with load for a relation. The test parameters were also tested during single apneic beats for a relation to inotropic interventions. Results: MPI demonstrated a strong and linear relationship to both preload and after-load, and this was due to changes in ejection time, and not the isovolumic intervals. Long axis segmental dyssynchrony increased during each hour of endotoxin infusion and global myocardial injury. This dysynchrony parameter was independent of load when tested by IVCBO. Peak systolic velocities were strongly load-independent, though not in all the inotropic situations and by all measurement axes. Peak systolic strain was load-dependent, and not strongly related to inotropic conditions. Peak systolic LV twist and untwist were strongly load-dependent. Conclusions: MPI is strongly load-dependent, and can vary widely in value for the same contractile status if the load is varied. Mechanical dyssynchrony measures are load-independen in health and also in early global endotoxin myocardial injury and dysfunction. Peak sytole velocities are a clinically robust parameter of LV regional and global performance under changing load, though peak systolic strain seems to be load-dependent. Left ventricular twist and untwist are load-dependent in this pig model.
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| 60. |
- Arvidsson, Sandra, 1986-
(författare)
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Cardiac function in hereditary transthyretin amyloidosis : an echocardiographic study
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Hereditary transthyretin amyloidosis (ATTR) is a lethal disease in which misfolded transthyretin (TTR) proteins accumulate as insoluble aggregates in tissues throughout the body. A common mutation is the exchange of valine to methionine at place 30 (TTR V30M), a form endemically found in the northern parts of Sweden. The main treatment option for ATTR amyloidosis is liver transplantation as the procedure halts production of mutated transthyretin. The disease is associated with marked phenotypic diversity ranging from predominant cardiac complications to pure neuropathy. Two different types of fibril composition – one in which both fragmented and full-length TTR are present (type A) and one consisting of only full-length TTR (type B) have been suggested to account for some phenotypic differences. Cardiac amyloidosis is associated with increased myocardial thickness and the disease could easily be mistaken for other entities characterised by myocardial thickening, such as sarcomeric hypertrophic cardiomyopathy (HCM). The aims in this thesis were to investigate echocardiographic characteristics in Swedish ATTR amyloidosis patients, and to identify markers aiding in differentiating ATTR heart disease from HCM. Another objective was to examine the impact of fibril composition and sex on the phenotypic variation in amyloid heart disease.Methods: A total of 122 ATTR amyloidosis patients that had undergone thorough echocardiographic examinations were included in the studies. Analyses of ventricular geometry as well as assessment of systolic and diastolic function were performed, using both conventional echocardiographic methods and speckle tracking technique. ECG analysis was conducted in study I, allowing measurement of QRS voltage. In study I and study II ATTR patients were compared to patients with HCM. In addition, 30 healthy controls were added to study II.Results: When parameters from ECG and echocardiography were investigated, the results revealed that the combination of QRS voltage <30 mm (<3 mV) and an interventricular/posterior wall thickness quotient <1.6 could differentiate cardiac ATTR amyloidosis from HCM. Differences in degree of right ventricular involvement were also demonstrated between HCM and ATTR amyloidosis, where ATTR patients displayed a right ventricular apical sparing pattern whereas the inverse pattern was found in HCM. Analysis of fibril composition revealed increased LV wall thickness in type A patients compared to type B, but in addition type A women displayed both lower myocardial thickness and more preserved systolic function as compared to type A males. When cardiac geometry and function were evaluated pre and post liver transplantation in type A and B patients, significant deterioration was detected in type A but not in type B patients after liver transplantation.Conclusions: Increasing awareness of typical cardiac amyloidotic signs by echocardiography is important to reduce the risk of delayed diagnosis. Our classification model based on ECG and echocardiography could aid in differentiating ATTR amyloidosis from HCM. Furthermore, the apical sparing pattern found in the right ventricle may pose another clue for amyloid heart disease, although it requires to be studied further. Furthermore, we disclosed that type A fibrils, male sex and increasing age were important determinants of increased myocardial thickness. As type A fibril patients displayed rapid cardiac deterioration after liver transplantation other treatment options should probably be sought for this group of patients.
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