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61.
  • Asayesh, Amir, 1977- (författare)
  • Spleno-pancreatic development assessed by 3D molecular imaging
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The development of different organs and tissues along the gastrointestinal tract, including the pancreas, depends on signalling between the endoderm and the adjacent mesenchyme. The Nkx gene Bapx1 is involved in spatial control of organ-positioning in the spleno-pancreatic region, and deficiency in this gene results in unacceptable proximity of the splenic mesenchyme to the pancreas. This permits agitating signals from the splenic mesenchyme to induce an in vivo (and in vitro) transformation of pancreatic epithelium to a cystic structure with gut like features. Also, wild type splenic mesenchyme is competent to induce a similar transformation. These findings illustrate the importance for strict control of organ positioning during spleno-pancreatic development. Several growth factors and receptors involved in pancreatic development are activated by protease processing. Some of these growth factors have been implicated as substrates for members of the A Disintegrin And Metalloprotease (ADAM) family. The ADAMs 9, 10, and 17 are expressed during pancreatic development and in the adult pancreas, suggesting a possible role for these ADAMs in pancreatic development and function. Animal model systems are widely used to investigate gene function during development and disease. However, spatial, molecular, and quantitative phenotype screening in animals is a time consuming effort. Optical Projection Tomography is a 3-dimensional imaging technique that, in combination with improvements in sample preparation and computer processing, can be used to visualize and quantify characteristics of intact adult mouse organs such as the total β-cell content in the pancreas.
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62.
  • Asklund, Ina, 1978- (författare)
  • A mobile app for self-management of urinary incontinence : treatment effect and user experience
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background Urinary incontinence affects 25-45% of all women. The most common type is stress urinary incontinence, which is the leakage of urine on physical exertion. Pelvic floor muscle training is an effective first-line treatment for this condition but many women do not seek help from their ordinary health care service. There is a need to evaluate new methods to offer effective treatment, and internet-based treatment has previously been found to be effective for women with stress urinary incontinence.Aim To evaluate the mobile app Tät® which has a self-management program focused on pelvic floor muscle training for women with stress urinary incontinence, with respect to treatment effect, factors associated with successful treatment, user experience and use by pregnant and postnatal women.Methods Papers I, II and III are based on the same study population from a randomized controlled trial (RCT). We recruited adult women who had stress urinary incontinence at least weekly via our website. In total, 123 women  were randomized to the app group (n=62) or the control group (n=61). The app included information about incontinence, the pelvic floor and lifestyle factors associated with incontinence, pelvic floor muscle training exercises and functions for reminders and training statistics. Treatment outcome after three months was evaluated using validated questionnaires assessing incontinence symptoms, quality of life, subjective improvement and a leakage diary. Outcomes were compared between the two groups. Factors associated with a successful outcome in the app group were further analysed using logistic regression. We strategically selected 15 women who had used the app and interviewed them about their experiences of using the app. The interviews were analysed according to Grounded Theory. After closing the RCT we made the app freely available and continued to follow its use on a larger scale by incorporating an anonymous questionnaire that appeared within the app upon download and after three months. The data from these questionnaires is used in paper IV.  Results Participants in the RCT had a mean age of 44.7 years (range 27-72) and 120 of the 123 women had moderate/severe incontinence. The app group reported significant improvements in the primary outcomes, the incontinence symptom score (mean ICIQ-UI SF reduction 3.9, 95% CI 3.0-4.7) and the quality of life score (mean ICIQ LUTSqol reduction 4.8, 95% CI 3.4-6.2), and the difference between the groups was significant. The app group also reduced their number of leakages and use of incontinence aids compared to the control group. At follow-up 92% of women in the app group experienced subjective improvement and 56% had improved “much” or “very much” and were classified as having a successful treatment outcome.Factors associated with a successful outcome were higher expectations of treatment effect (OR 11.38, 95% CI 2.02-64.19), weight control (OR 0.44 per kg gained, 95% CI 0.24-0.79), and self-assessed improvement of pelvic floor muscle strength (OR 35.54, 95% CI 4.96-254.61).The main finding from the interviews was that women experienced that the app “enabled their independence”. They described that the app was “something new” that helped with “keeping motivation up” although they sometimes wondered whether their training efforts were “good enough”.The freely available app was downloaded by 10,456 pregnant and postnatal women during a period of ten months (41% of all users). At inclusion 51% experienced incontinence and their mean ICIQ-UI SF score was 6.7 (SD 3.45). After three months, 1,805 women answered the follow-up. The majority of women with incontinence at inclusion experienced improvement with greater improvement in the postnatal group than in the pregnant group.Conclusion The mobile app Tät® offers a new, easily accessible and effective self-management program for women with stress urinary incontinence. Women appreciated that the app enabled them to manage their pelvic floor muscle training independently. Once the app was freely released it reached a large population with many pregnant and postnatal women. We believe that the app could be useful for the prevention of urinary incontinence among pregnant women. We also believe that the app could be used both as a stand-alone treatment and as a complement to other treatments provided by the ordinary health care service.
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63.
  • Aspholm, Marina, 1972- (författare)
  • Adaptation of Helicobacter pylori Adherence Properties in Promotion of Host Tropism and Inflammatory Disease
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Being among the most prevalent of persistent infectious agents in humans worldwide, Helicobacter pylori induces chronic inflammation (gastritis), which may progress to peptic ulceration and stomach cancer. The ability to adhere to the gastric mucosa is considered to be both a colonization and virulence property of H. pylori. For adherence, H. pylori expresses surface-located attachment proteins (adhesins) that bind to specific receptors in the gastric mucosa. The best characterized H. pylori adhesin-receptor interaction is that between the blood group antigen binding adhesin (BabA) and the fucosylated blood group antigens, which are glycans highly expressed in the gastric mucosa. Our recent results have changed the view of the blood group antigen-specific binding mode of H. pylori. We have tested clinical isolates of H. pylori from human populations worldwide for their ability to bind to ABO blood group antigens. The results revealed that more than 95% of isolates from Sweden, Germany, Spain, Japan and Alaska that bind fucosylated blood group antigens, bind both the Lewis b antigen (Leb) (of blood group O) and the blood group A-related antigen A-Lewis b, i.e. they exhibit a generalist type of binding mode. In contrast, the majority of strains (62%) from South American Amerindians bound best to Leb, i.e. they exhibit a specialist blood group “O antigen” binding mode. This specialization in binding coincides with the unique predominance of blood group O in the South American Amerindian populations. Furthermore, we also showed that H. pylori could switch from specialist to generalist binding modes by chromosomal integration of foreign babA gene fragments. A mutant strain lacking the babA gene turned out to adhere to inflamed gastric epithelium, despite the fact that it did not bind Leb. We identified the receptor to which the mutant binds to as the sialyl-dimeric-Lewis x antigen (sdiLex) and found its expression to be associated with persistent H. pylori infection and chronic inflammation, both in humans and Rhesus monkeys. The cognate sialic acid binding adhesin (SabA) was identified by our ReTagging technique. Deletion of sabA caused loss of H. pylori binding to sialylated glycans, and screening of single colony isolates revealed a high frequency of spontaneous on⇒off phase variation in sLex binding. Using erythrocytes as a model for sialyl dependent cell adhesion, we could show that SabA is the sought-after H. pylori sialyl-dependent hemagglutinin. Swedish clinical H. pylori isolates were analyzed for sialyl-dependent hemagglutination (sia-HA), and the sia-HA titers were found to be highly correlated to the levels of sLex binding. Clinical isolates were shown to exhibit several distinct binding modes for sialylated glycans, which suggest that SabA exhibit polymorphism in binding. We also found that SabA binds to sialylated glycans on neutrophil surfaces by mechanisms involving “selectin mimicry”, and that SabA plays an important role in nonopsonic activation of neutrophils. In the human stomach, H. pylori is exposed to selective pressures such as immune and inflammatory responses, and this is reflected by changes in mucosal glycosylation patterns. The high mutation and recombination rates of H. pylori in combination with bio selection will continuously generate clones that are adapted to changes in individual gastric mucosa. Such adaptive selection contributes to the remarkable diversity in binding modes and to the extraordinary chronicity of H. pylori infections worldwide.
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64.
  • Asplund, Pär, 1974- (författare)
  • Percutaneous Balloon Compression for the Treatment of Trigeminal Neuralgia
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background. Trigeminal neuralgia (TN) is a paroxysmal unilateral facial pain condition. That it is rather rare is of little comfort to those who are affected, as TN is often described as one of the worst pains known to mankind. Advanced age and multiple sclerosis (MS) are risk factors for developing TN. The first line of treatment is medical, primarily with carbamazepine. When medical treatment fails, as it does in many patients, there are several surgical options. One of the minimally invasive options, suitable for patients with comorbidity, is percutaneous balloon compression (PBC). Despite its introduction in the early 1980s, PBC is arguably the least well studied of the minimally invasive procedures for the treatment of TN.Aims. The aim of this thesis was to evaluate the efficacy of PBC, both overall and in MS-TN patients specifically. Further, it intended to identify and evaluate pre- and intraoperative parameters associated with the efficacy of PBC. It also investigated changes in sensory function after PBC, and identified side effects and complications associated with PBC. Finally, it sought to evaluate how efficacy, side effects and complications differed between PBC and another minimally invasive technique; percutaneous retrogasserian glycerol rhizotomy (PRGR).Methods. Cohorts of patients treated with PBC in Umeå and Stockholm, and with PRGR in Umeå, were followed retrospectively. Data from an existing database was combined with data from medical records, radiographs and telephone interviews.Results. After PBC, 90 % of the patients were completely pain free without medication for TN. The median time to recurrence of pain was 28 months. In patients with concurrent MS, the initial success rate was 67 % and the median time to recurrence was 8 months. In patients without MS, who had not previously been treated surgically, the initial success rate was 91 % and the median time to recurrence was 48 months. The procedure could, however, be repeated with good results. A good compression, indicated by a pear-shaped balloon as seen on intraoperative lateral radiograph, was crucial to achieve good pain relief. Postoperative hypoesthesia was present in the majority of patients, but after 3-6 months, sensibility was partly or fully normalized in most patients. Severe complications were rare, but included transient cardiac arrest, meningitis and dysesthesia. The side effects profile was favorable to that of percutaneous retrogasserian glycerol rhizotomy, in that the latter produced more cases of dysesthesia and decreased corneal sensibility. The efficacy of the two treatments were, however, not significantly different.Conclusions. PBC is an effective and relatively safe treatment option for patients with TN refractory to medical treatment. It deserves its place among the standard treatments for TN, and could be considered for those patients eligible for surgery for which open surgery is a less suitable option. 
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65.
  • Asplund, Sofia, 1982- (författare)
  • Work-related stress among municipal employees in rural northern Sweden
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Many rural municipalities in Sweden are facing challenges like depopulation, decreased economy, and difficulties in recruiting staff. Living and working in rural areas may involve adverse working conditions and higher risks of ill-health. Work is generally good for employee health, but various physical and psychosocial aspects of work can also be hazards and cause work-related stress, health problems, reduced productivity, and long-term sick leave. Leadership by managers in the organisation is important for the work environment, work performance, and occupational health of employees. The Swedish municipal sector employs almost 20% of employees in the labour market, where school, preschool and care of older people are the dominating areas. Previous research has shown that there are adverse psychosocial working conditions in Swedish municipal organisations. The municipal sector has the highest rate of long-term sick leave compared to other sectors in the labour market, mainly due to stress-related disorders, such as exhaustion disorder (ED). Therefore, it is important to focus on organisational and psychosocial work environments, work-related stress, and health in the municipal sector of rural northern Sweden.Aim: The overall aim was to explore organisational and psychosocial work environments, work-related stress, and health among municipal employees in rural northern Sweden.Methods: Both quantitative and qualitative methods were used to collect data. Study I and II had a quantitative approach, a cross-sectional design, and used a questionnaire for collecting data. Participants were employees (n =1093) in the municipal sector in two municipalities in rural northern Sweden. The questionnaire was constructed to contain instruments measuring the organisational and psychosocial work environments, perceived stress, self-rated exhaustion disorder (s-ED), and physical activity. Quantitative data were analysed using logistic regression in Study I, and partial least squares regression in Study II. Studies III and IV had a qualitative approach. In Study III, semi-structured individual interviews were conducted with 15 municipal employees with high self-reported stress. In Study IV, semi-structured individual interviews were conducted with 15 managers at different levels in the municipal sector. All qualitative data were analysed using inductive qualitative content analysis.Results: In Study I, results showed that 21.5 % of the municipal employees reported s-ED.Cognitive problems, sleep problems,depressiveivsymptoms, high stress, poor self-rated health, and stomach problems were the health-related factors most strongly associated with s-ED. In Study II, results showed that there were significant differences between the s-ED and the non–s-ED group in all but one of the 32 organisational and psychosocial environmental work factors. Various demands—i.e., quantitative, emotional, intellectual—and work conflicts were important factors associated with s-ED. Social support, resources, and time for work and reflection were important factors associated with non–s-ED. Findings from Study III showed that the employees with high self-reported stress experienced feelings of suffering through endless chaos when they worked in an organisation with high demands and low resources, control, and support. They also experienced feelings of insufficiency, and negative effects on health and family life. Findings from Study IV showed that managers in the municipal sector experienced feelings of striving for stability on shaky ground. They struggled inside slimmed-down organisations with a substitute shortage and reduced means, were burdened by conflicting demands, and experienced health and family life impairments. Managers expressed the importance of motivation, social support, and coping strategies.Conclusion: This thesis illuminates adverse psychosocial working conditions among municipal employees in two municipalities in the rural context of northern Sweden, where a stressful work environment, s-ED and health impairments are relatively common.It also provides important insights of municipal employee’s experiences of work-related stress, the importance of acknowledging suffering, and managers’ experiences of working in municipal organisations with shrinking resources, as in addition to a work–family imbalance. It seems important that organisations in the municipal sector have supportive and effective leadership, and allow employees control over their work. Furthermore, it seems important that various demands are balanced by sufficient resources; such as staff, social support, and economic resources in order to prevent work-related stress. Findings from this thesis can contribute to future interventions, aiming to prevent work-related stress and improve occupational well-being and work performance. They also have value for development work in municipal organisations.
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66.
  • Athanassiadis, Tuija, 1971- (författare)
  • Neural circuits engaged in mastication and orofacial nociception
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • A deeper understanding of both movement control and the effects of nociceptor inputs on our motor systems is critical for proper clinical diagnosis of musculo-skeletal dysfunctions and for development of novel rehabilitation schemes. In the jaw system, masticatory movements are produced by a central pattern generator (CPG) located in the brainstem. Considerable efforts have been made in deciphering this neuronal network. The present thesis contributes towards an increasingly detailed understanding of its essential elements, and presents a hypothesis of how deep somatic pain (i.e. muscle pain) may be evoked and interferes with the masticatory CPG circuitry. In Paper I, the expression of c-Fos-like protein was used as a molecular marker to visualize brainstem neurons that were active during induced fictive mastication in the anesthetized and paralyzed rabbit. Our findings provide a previously lacking detailed record of the neuronal populations that form the masticatory motor pattern. Certain cells were located in brainstem areas previously suggested to be involved in the masticatory CPG. However, it was a new finding that neurons in the dorsal part of the trigeminal main sensory nucleus (NVsnpr-d) may belong to this circuitry. Paper II focused on the discovered neurons in NVsnpr in an in vitro slice preparation from young rats.  Intracellular recordings allowed us to define two cell types based on their response to depolarizing current. Microstimulation applied to the trigeminal motor nucleus, its reticular border, the parvocellular reticular formation and the nucleus reticularis pontis caudalis, elicited postsynaptic potentials in 81% of the neurons tested. Responses obtained were predominately excitatory and sensitive to gluta-matergic antagonists DNQX or/and APV. Some inhibitory and biphasic responses were also evoked. Bicuculline methiodide or strychnine blocked the IPSPs indicating that they were mediated by GABAA or glycinergic receptors. About one third of the stimulations activated both types of neurons antidromically. Neurons in NVsnpr-d seem to gather all the conditions that can theoretically account for a role in masticatory rhythm generation. In Paper III, the masticatory model system was used to investigate the possible role of muscle spindle primary afferents in development of persistent musculoskeletal pain. Following intramuscular acidic (pH 4.0) saline injections of rat masseter muscles, in vitro whole cell recordings were done from jaw closing muscle spindle somata located in the trigeminal mesencephalic nucleus (NVmes). Compared to control neurons, the somata of afferents exposed to acid had more hyperpolarized membrane potentials, more hyperpolarized thresholds for firing, high frequency membrane oscillations and ectopic bursting of action potentials. These changes in membrane properties lasted for up to 35 days. Within the same time frame experi-mental animals showed hypersensitivity to touch on the skin covering the injected muscle. Similar saline injections also resulted in a significant increase of activity dependent c-Fos expression in NVmes neurons compared to controls. Immuno-fluorescence and lectin binding studies indicated that small-caliber muscle afferents containing known nociceptor markers (CGRP, SP, P2X3, TRPV1 and IB4) and expressing glutamate receptors are found close to the annulo-spiral endings of the NVmes afferents. Combined, our new observations support the hypothesis that excessive release of glutamate, within muscle spindles due to ectopically evoked antidromic action potentials, could lead to development of persistent musculoskeletal pain by activation and/ or sensitization of adjacent muscle afferent nociceptors.
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67.
  • Avican, Kemal, 1980- (författare)
  • Persistent infection by Yersinia pseudotuberculosis
  • 2015
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Enteropathogenic Yersinia species can infect many mammalian organs such as the small intestine, cecum, Peyer’s patches, liver, spleen, and lung and cause diseases that resemble a typhoid-like syndrome, as seen for other enteropathogens. We found that sublethal infection doses of Y. pseudotuberculosis gave rise to asymptomatic persistent infection in mice and identified the cecal lymphoid follicles as the primary site for colonization during persistence. Persistent Y. pseudotuberculosis is localized in the dome area, often in inflammatory lesions, as foci or as single cells, and also in neutrophil exudates in the cecal lumen. This new mouse model for bacterial persistence in cecum has potential as an investigative tool for deeper understanding of bacterial adaptation and host immune defense mechanisms during persistent infection. Here, we investigated the nature of the persistent infection established by Y. pseudotuberculosis in mouse cecal tissue using in vivo RNA-seq of bacteria during early and persistent stages of infection. Comparative analysis of the bacterial transcriptomes revealed that Y. pseudotuberculosis undergoes transcriptional reprogramming with drastic down-regulation of T3SS virulence genes during persistence in the cecum. At the persistent stage, the expression pattern in many respects resembles the pattern seen in vitro at 26°C. Genes that are up-regulated during persistence are genes involved in anaerobiosis, chemotaxis, and protection against oxidative and acidic stress, which indicates the influence of different environmental cues. We found that the Crp/CsrA/RovA regulatory cascades influence the pattern of bacterial gene expression during persistence. Furthermore, we show that ArcA, Fnr, FrdA, WrbA, RovA, and RfaH play critical roles in persistence. An extended investigation of the transcriptional regulator rfaH employing mouse infection studies, phenotypic characterizations, and RNA-seq transcriptomics analyses indicated that this gene product contributes to establishment of infection and confirmed that it regulates O-antigen biosynthesis genes in Y. pseudotuberculosis. The RNA-seq results also suggest that rfaH has a relatively global effect. Furthermore, we also found that the dynamics of the cecal tissue organization and microbial composition shows changes during different stages of the infection. Taken together, based on our findings, we speculate that this enteropathogen initiates infection by using its virulence factors in meeting the innate immune response in the cecal tissue. Later on, these factors lead to dysbiosis in the local microbiota and altered tissue organization. At later stages of the infection, the pathogen adapts to the environment in the cecum by reprogramming its transcriptome from a highly virulent mode to a more environmentally adaptable mode for survival and shedding. The in vivo transcriptomic analyses for essential genes during infections present strong candidates for novel targets for antimicrobials.
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68.
  • Awad, Amar, 1988- (författare)
  • Functional brain imaging of sensorimotor dysfunction and restoration : investigations of discomplete spinal cord injury and deep brain stimulation for essential tremor
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The nervous system exists to generate adaptive behaviour by processing sensory input from the body and the environment in order to produce appropriate motor output, and vice versa. Consequently, sensorimotor dysfunction is the basis of disability in most neurological pathologies. In the current thesis, I explore two conditions with different types and degrees of sensorimotor dysfunction by means of functional magnetic resonance imaging (fMRI). In part 1, I assess residual sensory connections to the brain in clinically complete spinal cord injury (SCI) with seemingly complete loss of sensorimotor function below the injury level. In part 2, fMRI is combined with deep brain stimulation (DBS) to investigate interventional mechanisms of restoring dysfunctional sensorimotor control in essential tremor (ET).Part 1: SCI disrupts the communication between the brain and below-injury body parts, but rarely results in complete anatomical transection of the spinal cord. In studies I and II, we demonstrate somatosensory cortex activation due to somatosensory (tactile and nociceptive) stimulation on below-level insensate body parts in clinically complete SCI. The results from studies I and II indicate preserved somatosensory conduction across the spinal lesion in some cases of clinically complete SCI, as classified according to international standards. This subgroup is referred to as sensory discomplete SCI, which represents a distinct injury phenotype with an intermediate degree of injury severity between clinically complete and incomplete SCI.Part 2: ET is effectively treated with DBS in the caudal zona incerta, but the neural mechanisms underlying the treatment effect are poorly understood. By exploring DBS mechanisms with fMRI, DBS was shown to cause modulation in the activity of the sensorimotor cerebello-cerebral regions during motor tasks (study III), but did not modulate the functional connectivity during resting-state (study IV).fMRI is a valuable tool to investigate sensorimotor dysfunction and restoration in SCI and DBS-treated ET. There is evidence for sensory discomplete SCI in about half of the patients with clinically complete SCI. DBS modulates DBS modulation of the activity in the sensorimotor cerebello-cerebral circuit during motor tasks, but not during resting-state, is action-dependent.
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69.
  • Axelsson, Birger, 1957- (författare)
  • Cardiac effects of non-adrenergic inotropic drugs : clinical and experimental studies
  • 2013
  • 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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70.
  • Axelsson, Karin (författare)
  • Eating problems and nutritional status after stroke
  • 1988
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Eating problems and nutritional status were studied in a consecutive series of 104 stroke patients admitted to emergency hospital care. During their stay in hospital eating problems were observed in 46 patients. Certain common types of eating problems were identified: aberrant eating behaviour as regards chewing,lokalization or swallowing, eating small amounts, hoarding of food in the mouth, leakage of food from the mouth and unawareness of eating problems. Poor nutritional status occurred in 16 % of the patients on admission and in 22 % on discharge from the stroke unit.A subgroup of 32 patients hospitalized for 21 days or longer was studied for three weeks. On at least one occasion during these three weeks a poor nutritional status was observed in 18 patients, of whom 17 had eating problems.All subjects who had eating problems during their hospital stay, plus those patients without eating problems but with neurological deficits and those living in a nursing home one year after the stroke (n=36) were selected for a longitudinal study 18 months after the onset of stroke. Eating problems were identified in 23 of these patients during their hospital stay while 21 had such problems when they were followed up.Two patients who could not eat due to severe dysphagia (after a stroke) for three years and 18 months respectively, were successfully trained to eat normally. One patient exhibited impaired oral and hypopharyngeal function and the other impaired hypo- pharyngeal function and a spastic crico-pharyngeal muscle. In both patients training in swallowing was the main remedical measure and one of them also had a myotomy of the spastic muscle.
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