| 11. |
- Andersson, Kennet, 1979-
(författare)
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Assessment of cerebrospinal fluid system dynamics : novel infusion protocol, mathematical modelling and parameter estimation for hydrocephalus investigations
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients with idiopathic normal pressure hydrocephalus (INPH) have a disturbance in the cerebrospinal fluid (CSF) system. The treatment is neurosurgical – a shunt is placed in the CSF system. The infusion test is used to assess CSF system dynamics and to aid in the selection of patients that will benefit from shunt surgery. The infusion test can be divided into three parts: a mathematical model, an infusion protocol and a parameter estimation method. A non-linear differential equation is used to mathematically describe the CSF system, where two important parameters are the outflow conductance (Cout) and the Pressure Volume Index (PVI). These are used both for clinical and research purposes. The analysis methods for the non-linear CSF system have limited the infusion protocols of presently used infusion investigations. They come with disadvantages such as long investigation time, no estimation of PVI and no measure of the reliability of the estimates.The aim of this dissertation was to develop and evaluate novel methods for infusion protocols, mathematical modelling and parameter estimation methods for assessment of CSF system dynamics.The infusion protocols and parameter estimation methods in current use, constant pressure infusion (CPI), constant infusion and bolus infusion, were investigated. The estimates of Cout were compared, both on an experimental set-up and on 20 INPH patients. The results showed that the bolus method produced a significantly higher Cout than the other methods. The study suggested a method with continuous infusion for estimating Cout and emphasized that standardization of Cout measurement is necessary.The non-linear model of the CSF system was further developed. The ability to model physiological variations that affect the CSF system was incorporated into the model and it was transformed into a linear time-invariant system. This enabled the use of methods developed for identification of such systems. The underlying model for CSF absorption was discussed and the effect of baseline resting pressure (Pr) in the analysis on the estimation of Cout was explored using two different analyses, with and without Pr.A novel infusion protocol with an oscillating pressure pattern was introduced. This protocol was theoretically better suited for the CSF system characteristics. Three new parameter estimation methods were developed. The adaptive observer was developed from the original non-linear model of the CSF system and estimated Cout in real time. The prediction error method (PEM) and the robust simulation error (RSE) method were based on the transformed linear system, and they estimated both Cout and PVI with confidence intervals in real time. Both the oscillating pressure pattern and the reference CPI protocol were performed on an experimental set-up of the CSF system and on 47 hydrocephalus patients. The parameter estimation methods were applied to the data, and the RSE method produced estimates of Cout that were in good agreement with the reference method and allowed for an individualized and considerably reduced investigation time.In summary, current methods have been investigated and a novel approach for assessment of CSF system dynamics has been presented. The Oscillating Pressure Infusion method, which includes a new infusion protocol, a further developed mathematical model and new parameter estimation methods has resulted in an improved way to perform infusion investigations and should be used when assessing CSF system dynamics. The advantages of the new approach are the pressure-regulated infusion protocol, simultaneous estimation of Cout and PVI and estimates of reliability that allow for an individualized investigation time.
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| 12. |
- Andersson, Therése, 1978-
(författare)
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Estrogen and Glucocorticoid Metabolism
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Cardiovascular disease (CVD) is the leading cause of death among women in Sweden. The risk of CVD increases rapidly after the menopause. A major contributing factor may be the redistribution of adipose tissue, from the peripheral to central depots, associated with menopause. This change in body composition is commonly attributed to declining estrogen levels but may also be affected by tissue-specific alterations in exposure to other steroid hormones, notably glucocorticoids – mainly cortisol in humans. Indeed, adipose tissue-specific overexpression of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) induces central obesity, insulin resistance and hypertension in mice. Interestingly, estrogen may regulate this enzyme. The aim of this thesis was to investigate putative links between estrogen and glucocorticoid activation by 11βHSD1. Materials and Methods: 11βHSD1 expression and/or activity in adipose tissue and liver, and adipose estrogen receptor α and β (ERα and ERβ) gene expression, were investigated in lean pre- and postmenopausal women and ovariectomized rodents with and without estrogen supplementation. In lean women measures of 11βHSD1 were correlated to risk markers for CVD. The association between adipose 11βHSD1 and ER mRNA expression was investigated in both lean women and rats and in an additional cohort of obese premenopausal women. In vitro experiments with adipocyte cell lines were used to explore possible pathways for estrogen regulation of 11βHSD1. Results: Subcutaneous adipose tissue transcript levels and hepatic activity of 11βHSD1 were higher in postmenopausal vs. premenopausal women. In rodents, estrogen treatment to ovariectomized rats decreased visceral adipose tissue 11βHSD1, resulting in a shift towards higher subcutaneous (vs. visceral) 11βHSD1 mRNA expression/activity. Increased adipose and hepatic 11βHSD1 were associated with increased blood pressure and a disadvantageous blood lipid profile in humans. We found significant positive associations between 11βHSD1 and ERβ transcript levels in adipose tissue. The in vitro experiments showed upregulation of 11βHSD1 mRNA expression and activity with estrogen or ERβ-agonist treatment at low (corresponding to physiological) concentrations. Conclusions: Our studies show for the first time increased local tissue glucocorticoid activation with menopause/age in women. This may contribute to an increased risk of CVD. Estrogen treatment in rodents induces a shift in 11βHSD1 activity towards the subcutaneous adipose tissue depots, which may direct fat accumulation to this metabolically “safer” depot. The in vitro studies suggest that low-dose estrogen treatment upregulates 11βHSD1 via ERβ. In summary, estrogen - glucocorticoid metabolism interactions may be key in the development of menopause-related metabolic dysfunction and in part mediate the beneficial effects of postmenopausal estrogen treatment on body fat distribution.
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| 13. |
- 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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| 14. |
- 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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| 15. |
- 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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| 16. |
- 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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| 17. |
- 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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| 18. |
- Axelsson, Birger, 1957-
(författare)
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Cardiac effects of non-adrenergic inotropic drugs : clinical and experimental studies
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Myocardial failure and dysfunction is not uncommon during critical illness and following cardiac surgery. For optimal treatment, a better understanding of the effects of inotropic drugs is needed. In this thesis, two non-adrenergic mediated inotropes, milrinone and levosimendan were studied in different models of myocardial dysfunction. The study aims were to assess the following: the effects of milrinone on blood flow in coronary artery bypass grafts during CABG surgery; the effects of milrinone on left ventricular diastolic function during post-ischaemic myocardial dysfunction; whether milrinone or levosimendan are protective or injurious during acute myocardial ischaemia, and if levosimendan potentiates myocardial function when added to milrinone in an experimental model of post-ischaemic (stunned) myocardium.Material and Methods: In Study I, 44 patients undergoing coronary artery bypass surgery(CABG) were included as subjects. Milrinone or saline was administrated in a single dose during cardio-pulmonary bypass (CPB) and coronary graft flow measurements were recorded after 10 and 30 min following CPB. In Study II; 24 patients undergoing CABG had estimations of peak ventricular filling rates made before and after CPB with administration of milrinone or saline as a single dose during CPB, performed by assessment of the rate of change in diastolic cross-sectional left ventricular area. In Study III, energy-metabolic effects of milrinone and levosimendan were measured in an anaesthetized porcine model during 45 minutes of regional myocardial ischemia. Microdialysis sampling of metabolites of local ischemic metabolism allowed assessment of glycolytic activity and the degree of myocardial calcium overload. In Study IV, in a porcine model of postischaemic myocardial stunning, ventricular pressure-volume relationships were analyzed when milrinone or a combination of milrinone and levosimendan were given together.Results: In Study I, there was a clear increase in non-sequential saphenous vein graft blood flow with milrinone at 10 minutes (64.5 ± 37.4 compared to placebo 43.6 ± 25.7 ml/min (mean ± SD).). A decreasing but still measureable flow increase was seen for milrinone at 30 minutes. In Study II, an increase in early left ventricular filling rate (ventricular cross-sectional area rate of change,dA/dt) was seen in the milrinone treated group. Pre-bypass milrinone group dA/dt 22.0 ± 9.5 changed to post-bypass values dA/dt 27.8 ± 11.5 cm2/sec). Placebo group pre-bypass dA/dt was 21.0 ± 8.7 and post-bypass 17.1 ± 7.1 cm2/sec. A milrinone effect was demonstrated in an adjusted regression model (p = 0.001). In Study III, neither milrinone nor levosimendan led to a change in energy-metabolic activity during ischemia as reflected by interstitial glucose, pyruvate, lactate orglycerol. Neither drug exacerbated the relative myocardial calcium overload during ischemia. In Study IV, milrinone improved active relaxation (tau) in post-ischemic stunned myocardium, but did not markedly improve systolic function by preload recruitable stroke work. Levosimendan added to milrinone showed minimal effect on active relaxation but a positive effect on systolic function in combination with milrinone.Conclusions: We conclude that milrinone treatment leads to an increase in blood flow in newly implanted coronary saphenous vein grafts, and improves ventricular relaxation post-cardiopulmonary bypass. Neither milrinone nor levosimendan, in this porcine model, negatively influence myocardial energy metabolism or calcium overload during acute ischaemia. Addition of levosimendan to milrinone treatment during post-ischaemic ventricular dysfunction may provide additive inotropic effects on systolic function but probably not for active relaxation.
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| 19. |
- Backman, Ludvig, 1983-
(författare)
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Neuropeptide and catecholamine effects on tenocytes in tendinosis development : studies on two model systems with focus on proliferation and apoptosis
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Achilles tendinopathy is a common clinical syndrome of chronic Achilles tendon pain combined with thickening of the tendon and impaired tendon function. Tendinopathy is often, but not always, induced by mechanical overload, and is frequently accompanied by abnormalities at the tissue level, such as hypercellularity and angiogenesis, in which case the condition is called tendinosis. In tendinosis, there are no signs of intratendinous inflammation, but occasionally increased apoptosis is observed. Tendinosis is often hard to treat and its pathogenesis is still not clear. Recently, a new hypothesis has gained support, suggesting a biochemical model based on the presence of a non-neuronal production of classically neuronal signal substances by the primary tendon cells (tenocytes) in tendinosis. The possible functional importance of these signal substances in tendons is unknown and needs to be studied. In particular, the neuropeptide substance P (SP) and catecholamines are of interest in this regard, since these substances have been found to be up-regulated in tendinosis. As both SP and catecholamines are known to exert effects in other tissues resulting in changes similar to those characteristic of tendinosis, it is possible that they have a role in tendinosis development. It is furthermore unknown what elicits the increased intratendinous neuropeptide production in tendinosis, but given that tendon overload is a prominent riskfactor, it is possible that mechanical stimuli are involved.The hypothesis of this thesis work was that intratendinous production of SP is up-regulated in response to load of Achilles tendons/tenocytes, and thatstimulation of the preferred SP receptor, the neurokinin-1 receptor (NK-1 R), aswell as stimulation of the catecholamine α2 adrenoreceptors, contribute to the hypercellularity seen in tendinosis, via increased proliferation and/or decreased apoptosis, and that SP stimulates tendon angiogenesis. The purpose of the studies was to test this hypothesis. To achieve this, two model systems were used: One in vivo (rabbit Achilles tendon overload model of tendinosis) and one in vitro (human primary Achilles tendon cell culture model).Results: In the rabbit Achilles tendon tissue, SP and NK-1 R expression was extensive in the blood vessel walls, but also to some extent seen in the tenocytes. Quantification of endogenously produced SP in vivo confirmed intratendinous production of the peptide. The production of SP by human tendon cells in vitro was furthermore demonstrated. The catecholamine synthesizing enzyme tyrosine hydroxylase (TH), as well as the α2A adrenoreceptor (α2A AR), were detected in the tenocytes, both in vivo in the rabbit tissue and in vitro in the human tendon cells. As a response to mechanical loading in the in vivo model, the intratendinous levels of SP increased, and this elevation was found to precede distinct tendinosis changes. The in vitro model demonstrated the same response to load, i.e. an increased SP expression, but in this case also a decrease in the NK-1 R expression. In the in vivo model, exogenously administered SP, as well as clonidine (an α2 AR agonist), accelerated tenocyte hypercellularity, an effect that was not seen when administrating a specific α2A AR antagonist. Exogenous administration of SP also resulted in intratendinous angiogenesis and paratendinous inflammation. In the in vitro model, both SP and clonidine had proliferative effects on the human tenocytes, specifically mediated via NK-1R and α2A AR, respectively; both of which in turn involved activation/phosphorylation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2). Exogenously administered SP, in Anti-Fas induced apoptosis of the tenocytes in vitro, confirmed SP to have an anti-apoptotic effect on these cells. This effect was specifically mediated via NK-1 R and the known anti-apoptotic Akt pathway.Conclusions: In summary, this thesis concludes that stimulation of NK-1 R and α2A AR on tenocytes, both in vitro and in vivo, mediates significant cell signalling effects leading to processes known to occur in tendinosis, including hypercellularity. The pathological role of the hypercellularity in tendinosis is still unclear, but it is likely to affect collagen metabolism/turnover and arrangement, and thereby indirectly tendon biomechanical function. Additional evidence is here provided showing that SP not only causes tenocyte proliferation, but also contributes to anti-apoptotic events. Furthermore, it was concluded that SP may be involved in the development of tendinosis, since its production is increased in response to load, preceding tendinosis, and since SP accelerates tendinosis changes, through some mechanistic pathways here delineated. These findings suggest that inhibition of SP, and possibly also catecholamines, could be beneficial in the reconstitution/normalization of tendon structure in tendinosis.
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- Backteman-Erlanson, Susann, 1958-
(författare)
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Burnout, work, stress of conscience and coping among female and male patrolling police officers
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background. Police work is a stressful occupation with frequent exposure to traumatic events and psychological strain from work might increase the risk of burnout. This thesis focuses on patrolling police officers (PPO), who work most of their time in the community and have daily contact with the public. Since police work traditionally is a male coded occupation we assume that there are differences between women and men in burnout as well as experiences from psychosocial work environment.Aim. The overall aim of this thesis is to explore burnout, psychosocial and physical work environment, coping strategies, and stress of conscience when taking gender into consideration among patrolling police officers.Methods. This thesis employs both qualitative and quantitative methods. In Paper I a qualitative approach with narrative interviews was used where male PPO described experiences of traumatic situations when caring for victims of traffic accidents. A convenience sample of nine male PPO from a mid-sized police authority was recruited. Interviews were analyzed using qualitative content analysis. Papers II, III, and IV were based on a cross-sectional survey from a randomly selected sample stratified for gender from all 21 local police authorities in Sweden. In the final sample, 1554 PPOs were invited (778 women, 776 men), response rate was 55% (n=856) in total, 56% for women (n=437) and 53% for men (n=419). The survey included a self-administered questionnaire based on instruments measuring burnout, stress of conscience, psychosocial and physical work environment, and coping.Results. Findings from Paper I were presented in three themes; “being secure with the support system,” “being confident about prior successful actions,” and “being burdened with uncertainty.” Results from Paper II showed high levels of emotional exhaustion (EE), 30% for female PPOs and 26% for male PPOs. High levels of depersonalization (DP) were reported for 52 % of female PPO, corresponding proportions for male were 60%. Multiple logistic regression showed that stress of conscience (SCQ-A), high demand, and organizational climate increased the risk of EE for female PPO. For male PPO stress of conscience (SCQ-A), low control and high demand increased the risk of EE. Independent of gender, stress of conscience (SCQ-A) increased the risk of DP. Psychometric properties of the WOCQ were investigated with exploratory factor analysis and confirmatory factor analysis, a six-factor solution was confirmed. DIF analysis was detected for a third of the items in relation to gender. In Paper IV a block wise hierarchical multiple regression analysis was performed investigating the predictive impact of psychological demand, decision latitude, social support, coping strategies, and stress of conscience on EE as well as DP. Findings revealed that, regardless of gender, risk of EE and DP increased with a troubled conscience amongst the PPO.Conclusion. “Being burdened with uncertainty” in this male-dominated context indicate that the PPO did not feel confident talking about traumatic situations, which might influence their coping strategies when arriving to a similar situation. This finding can be related to Paper II and IV showing that stress of conscience increased the risk of both EE and DP. The associations between troubled conscience and the risk of experiencing both emotional exhaustion and depersonalization indicate that stress of conscience should be considered when studying the influence of the psychosocial work environment on burnout. Results from this study show that the psychosocial work environment is not satisfying and needs improvement for patrolling police officers in Sweden. Further studies including both qualitative and quantitative (longitudinal) methods should be used to improve knowledge in this area to increase conditions for preventive and rehabilitative actions.
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