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  • 1.
    Akner, G.
    et al.
    School of Health and Medical Sciences, Örebro University, 70185 Örebro, Sweden.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Personalized geriatric medicine2014Ingår i: European Geriatric Medicine, ISSN 1878-7649, E-ISSN 1878-7657, Vol. 5, nr 3, s. 145-146Artikel i tidskrift (Övrigt vetenskapligt)
  • 2.
    Andersson, Britta
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap.
    Manipulation of potassium ion fluxes to induce apoptosis in lung cancer cells2007Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Apoptosis is a special form of cell death that if non-functional may lead to diseases such as cancer. A reduction of the intracellular potassium ion (K+) content is necessary for activating enzymes important for the execution of apoptosis. Pharmacological modulation of K+ fluxes to reduce intracellular K+ in cancer cells might therefore force the cells into apoptosis and decrease tumour cell mass.

    Human malignant pleural mesothelioma (MPM) is a form of cancer often caused by asbestos exposure. Although asbestos has been banned in the Western World, the incidence of MPM is expected to increase. Cisplatin is the first-line chemotherapy for MPM, but acquired resistance to the drug is a clinical problem.

    This thesis is mainly based on work with the human malignant pleural mesothelioma cell line (P31 wt) and a cisplatin-resistant sub-line (P31 res). The aim was to first characterize K+ fluxes in P31 wt and P31 res cells, and then manipulate them in order to reduce intracellular K+ and induce apoptosis with K+ manipulation alone or in combination with cisplatin.

    Characterization of K+ fluxes in P31 wt cells showed that: 1) ouabain, a digitalis-like drug, and specific blocker of the Na+, K+, ATPase pump, effectively inhibited K+ uptake, 2) bumetanide, a diuretic, and an inhibitor of the Na+, K+, 2Cl-¬-cotransporter, had a transient effect on K+ uptake, and 3) the antifungal drug amphotericin B stimulated K+ efflux.

    In order to determine intracellular K+ content, the potassium-binding fluorescent probe PBFI-AM was used in a 96-well plate assay. After a 3-h incubation with ouabain, with or without bumetanide, combined with amphotericin B, the intracellular K+ content was reduced in P31 wt cells but not in P31 res cells.

    Ouabain induced apoptosis in both P31 wt and P31 res cells. P31 res cells were sensitized to cisplatin by ouabain, since 10 mg/L cisplatin in combination with ouabain induced about the same percentage of apoptotic cells as 40 mg/L cisplatin. Apoptosis was executed via caspase-3 activation in both P31 wt and P31 res cells. Amphotericin B enhanced ouabain-induced apoptosis in P31 wt cells via caspase-9 activation, with increased caspase-3 activation and DNA fragmentation as consequences. Ouabain-induced apoptosis in P31 res cells was executed via increased expression of pro-apoptotic Bak. The combination of cisplatin with ouabain and amphotericin B was stressful to both P31 wt and P31 res cells, since SAPK/JNK a known factor in stress-induced apoptosis was activated.

    In conclusion, K+ flux manipulation with clinical used drugs can induce apoptosis per se and also enhance cisplatin-induced apoptosis in P31 wt and P31 res cells.

  • 3.
    Andersson, Frida
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Logopedi.
    Karlsson, Olivia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Logopedi.
    Nationella bedömningsstödet i läsutveckling för årskurs 1: Ett värdefullt verktyg för pedagoger?2019Självständigt arbete på avancerad nivå (magisterexamen), 240 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Bakgrund 

    I svensk skola är ett av målenatt tidigt identifiera elever med nedsatt läsförmåga. För att underlätta identifieringen har ett nationellt bedömningsstöd arbetats fram. Nedsatt läsförståelse beror på nedsatt avkodningsförmåga eller nedsatt språkförståelse. Svårigheter med avkodning respektive språkförståelse kräver olika insatser i skolan.  

    Syfte 

    Syftet med studien var att undersöka om nationella bedömningsstödet för läsutvecklingi årskurs 1 identifierar andraelever änstandardiserade och normerade screeningtest genomfördai årskurs 2. Syftet var vidareatt undersöka om de elever som identifierats med nedsatt läsförmåga på nationella bedömningsstödet även uppvisar språkliga svårigheter samt hur pedagogerna använder resultatet på nationella bedömningsstödet för planering av vidare insatser. 

    Metod

    Studien omfattade 41 elever i årskurs 2 som genomfört nationella bedömningsstödet i årskurs 1 och DLS läsförståelse i årskurs 2. Eleverna testades med avkodningstesten Vilket är rätt?och Vilket låter rätt?och språkförståelsetestet TROG-2.Studien inkluderade även en intervju med 4 pedagoger som har ansvar för genomförandet av nationella bedömningsstödet.

    Resultat

    Nationella bedömningsstödet identifierade 13 elever med nedsatt läsförmåga i årskurs 1, screeningtesten DLS läsförståelseVilket är rätt?och Vilket låter rätt?identifierade 16 elever i årskurs 2. Screeningtesten identifierade 7 elever (44%) som inte identifierats på nationella bedömningsstödet. Nationella bedömningsstödet identifierade 2 elever med nedsatt språkförståelse. Samtliga pedagoger använder resultatet från nationella bedömningsstödet för planering av insatser. 

    Slutsatser

    Nationella bedömningsstödet fungerar till viss del i skolor där det utförs av pedagoger som är utbildade i nationella bedömningsstödet. Däremot identifierar nationella bedömningsstödet färre elever än standardiserade och normerade screeningtest och är mer tidskrävande. 

  • 4.
    Andersson, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Adipose tissue as an active organ:  blood flow regulation and tissue-specific glucocorticoid metabolism2011Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: Despite advances in the treatment of atherosclerosis, cardiovascular disease is the leading cause of death worldwide. With the population getting older and more obese, the burden of cardiovascular disease may further increase. Premenopausal women are relatively protected against cardiovascular disease compared to men, but the reasons for this sex difference are partly unknown. Redistribution of body fat from peripheral to central depots may be a contributing factor. Central fat is associated with hyperlipidemia, hyperglycemia, hypertension, and insulin resistance. Two possible mediators of these metabolic disturbances are tissue-specific production of the stress hormone cortisol and adipose tissue blood flow (ATBF). The aim of this thesis was to determine the adipose tissue production of cortisol by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and to investigate the regulation of ATBF.

    Materials and Methods: Cortisol release was estimated by labeled cortisol infusions and tissue-specific catheterizations of subcutaneous and visceral adipose tissue (VAT) in men. We investigated ATBF by 133Xe-washout and its relation to autonomic activity, endothelial function, adipose tissue distribution, and adipokines in different groups of women. We further investigated the effect of two diets and of weight loss on ATBF in women.

    Results: We demonstrated significant cortisol release from subcutaneous adipose tissue in humans. Splanchnic cortisol release was accounted for entirely by the liver. Cortisol release from VAT (to the portal vein) was not detected. ATBF decreased according to increasing weight and postmenopausal status, and the level of blood flow was associated with nitric oxide (NO) activity and autonomic activity. ATBF was also highly associated with leptin levels and both subcutaneous adipose tissue and VAT areas. After 6 months of diet and weight reduction, a significant difference in ATBF was observed between diet groups.

    Conclusions: Our data for the first time demonstrate the contributions of cortisol generated from subcutaneous adipose tissue, visceral tissues, and liver by 11β-HSD1. ATBF is linked to autonomic activity, NO activity, and the amount of adipose tissue (independent of fat depot). Postmenopausal overweight women exhibited a loss of ATBF flexibility, which may contribute to the metabolic dysfunction seen in this group. Weight loss in a diet program could not increase the ATBF, although there were ATBF differences between diet groups. The results will increase understanding of adipose tissue biology and contribute to the development of treatment strategies targeting obesity and obesity-related disorders.

  • 5.
    Andersson, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Karpe, Fredrik
    NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK.
    Sjöström, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Association of adipose tissue blood flow with fat depot sizes and adipokines in women2012Ingår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 36, nr 6, s. 783-789Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To explore possible associations between adipose tissue (AT) blood flow (ATBF), AT depot sizes and adipocyte-derived hormones (adipokines) in women.

    Subjects: In all, 43 healthy women were divided into four groups: normal-weight (n=11) and obese (n=11) pre-menopausal women and normal-weight (n=10) and obese (n=11) post-menopausal women.

    Methods: Fasting levels of adipokines were obtained, and a single-slice computed tomography scan at the level of L4-L5 was used to estimate fat depot sizes. ATBF was assessed by xenon washout while in a fasting state and after oral glucose load. We also measured glucose, insulin and non-esterified fatty acids.

    Results: Total, subcutaneous and visceral AT areas strongly correlated with ATBF (all P<0.001). Circulating leptin levels strongly and inversely correlated with ATBF (P=0.001), but this association did not remain after adjustment for body mass index. Adiponectin was not associated with blood flow.

    Conclusion: ATBF is closely linked to subcutaneous and visceral AT size. Further analyses are needed to determine possible mediators of this association, including mechanistic studies to assess a putative role for leptin as a significant modulator of blood flow. International Journal of Obesity advance online publication, 26 July 2011; doi:10.1038/ijo.2011.152.

  • 6.
    Andersson, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sjöström, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wiklund, Urban
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Centrum för medicinsk teknik och fysik (CMTF).
    Karpe, Fredrik
    NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK..
    Lindahl, Bernt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Long term effects of a diet intervention on adipose tissue blood flow, heart rate variability and endothelial function: a randomized controlled trialManuskript (preprint) (Övrigt vetenskapligt)
  • 7.
    Andersson, Jonas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sjöström, Lars-Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Karlsson, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hultin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Karpe, Fredrik
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Dysregulation of subcutaneous adipose tissue blood flow in overweight postmenopausal women2010Ingår i: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 17, nr 2, s. 365-371Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: A putative link between abdominal obesity and metabolic-vascular complications after menopause may be due to a decreased adipose tissue blood flow (ATBF). The present work aimed to analyze possible changes in ATBF with being overweight and menopausal and its putative link to endothelial dysfunction and autonomic nervous system balance.

    METHODS: Forty-three healthy women were classified into four groups according to weight and menopause status. The ATBF was measured by xenon washout while fasting and after oral glucose intake. The nitric oxide synthase inhibitor asymmetric dimethylarginine was used as a marker of endothelial function and heart rate variability-estimated autonomic nervous system activity.

    RESULTS: Fasting ATBF was decreased in both overweight groups (P = 0.044 and P = 0.048) versus normal-weight premenopausal women. Normal-weight and overweight postmenopausal women exhibited lower maximum ATBF compared with normal-weight premenopausal women (P = 0.015 and P = 0.001, respectively), and overweight postmenopausal women exhibited lower maximum ATBF compared with normal-weight postmenopausal women (P = 0.003). A negative correlation was found between fasting ATBF and asymmetric dimethylarginine (P = 0.015), whereas maximum ATBF was negatively associated with sympathetic-parasympathetic nervous system balance (ratio of the power of the low frequency to the power of the high frequency; P = 0.002).

    CONCLUSIONS: Loss of ATBF flexibility in overweight postmenopausal women may contribute to the metabolic dysfunction seen in this group of women.

  • 8.
    Andersson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Asthma in school age: prevalence, incidence and remission in relation to environmental determinants. The Obstructive Lung Disease in Northern Sweden (OLIN) Studies, Thesis XI2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background In the past half-century, the prevalence of asthma among children and adolescents has risen and asthma has become an important public health challenge in Sweden as well as in many other countries, necessitating further studies on this complex disease and its risk factor pattern. The studies included in this thesis aimed to investigate the clinical expression of childhood asthma over time, to describe the determinants of new-onset and remission of asthma, and to evaluate possible environmental risk factors in northern Sweden.

    Methods As the result of a repeated questionnaire survey among primary school children aged 7-8 years in three municipalities in the north of Sweden, two pediatric cohorts were formed, one in 1996 (n=3430) and one in 2006 (n=2585). The cohort created in 1996 was followed annually until the age of 19 years. Skin prick testing was performed on children in both cohorts. Lung function and bronchial hyperreactivity testing were carried out in children with asthma in the first cohort. The study participation and retention rates were very high in both cohorts. Among children in the second cohort living in Luleå, the home addresses were assigned to coordinates in a geographical information system (GIS) to evaluate the impact on respiratory health of living near roads with much traffic, which was measured as the number of vehicles daily. We used a validated reported diagnosis of asthma and International Study of Asthma and Allergies in Childhood (ISAAC) questions were incorporated into the questionnaire. A cross-sectional study of children of the same age ten years apart, longitudinal studies on asthma incidence and remission as well as a cross-sectional study on vehicle traffic were performed.

    Results While children aged 7-8 years in 2006 more often had a physician-diagnosed asthma compared to children of the same age in 1996 (7.4% vs 5.7%, p<0.001), they had less asthma symptoms, especially severe symptoms. In parallel, a more beneficial environment and a more intense treatment with inhaled corticosteroids (ICS) were observed. The explanation for this change in clinical expression probably includes also an increased awareness and diagnosing of asthma. From age 12 years to age 19 years, the cumulative incidence of physician-diagnosed asthma was 7.2% and of current wheeze 22.0%. The risk of new-onset asthma in adolescence was increased among girls, sensitized and those with heredity for asthma. Smoking and home dampness increased the risk for incident wheeze. The risk for both incident asthma and wheeze was inversely related to number of siblings. Among children with current asthma at age 7-8 years, 21% were in remission, 38% had periodic asthma and 41% had persistent asthma at a follow-up at age 19 years. Subjects in remission and with periodic asthma had significantly less airway obstruction and showed less bronchial hyperreactivity compared to subjects with persistent asthma. The probability of asthma remission from childhood to early adulthood was significantly increased by absence of allergic sensitization, male gender and a low asthma severity scoring at age 7-8 years. Sensitization to furred animals was more important as a determinant of both incidence and remission than sensitization to pollen. Living close to roads with high traffic flows, especially with heavy vehicles, was associated with an increased risk for current wheeze. Stratified analyses showed that the effect of traffic on asthma and wheeze was restricted to non-sensitized subjects.

    Conclusion Asthma onset in adolescence was more common among girls and remission was more common among boys. Children sensitized to furred animals and children with a more severe asthma were risk groups for persistence of asthma. Environmental factors such as smoking and dampness were associated to onset of asthma symptoms during adolescence, and vehicle traffic was associated with asthma symptoms among children also in a small city with relatively low traffic flows. Preventive measures like smoking reduction programs, improvement of damp housing conditions and separation of areas where many children live from heavily trafficked roads could prove to be beneficial.

  • 9.
    Arvidsson, Sandra
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Cardiac function in hereditary transthyretin amyloidosis: an echocardiographic study2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    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.

  • 10.
    Asplund, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Percutaneous Balloon Compression for the Treatment of Trigeminal Neuralgia2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    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.

     

  • 11.
    Asplund, Pär
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Linderoth, Bengt
    Lind, Göran
    Winter, Jaleh
    Bergenheim, A. Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    One hundred eleven Percutaneous Balloon Compressions for Trigeminal Neuralgia in a Cohort of 66 Patients with Multiple Sclerosis2019Ingår i: Operative neurosurgery, ISSN 2332-4252Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Trigeminal neuralgia associated with multiple sclerosis (MS-TN) is comparatively rare and larger series of percutaneous balloon compression (PBC) in such cases are few in the literature.

    OBJECTIVE: To evaluate the results after PBC for MS-TN with regards to therapeutic effect, side effects, and complications.

    METHODS: One hundred eleven procedures with PBC performed in 66 cases of MS-TN were analyzed. Therapeutic effect was measured as postoperative time to pain recurrence without medication. All complications were compiled and the sensory function was evaluated in a subgroup of cases.

    RESULTS: The initial pain free rate was 67% and the median time to pain recurrence was 8 mo. Thirty-six patients were treated with PBC only, and among them, the results were worse if treated 3 to 4 times before, compared to first treatment (P = .009-.034). Patients who had several PBCs had worse results already after the first surgery (P < .001). A significant number of patients had impaired sensation to light touch directly after surgery, which was normalized at the late follow-up. Sensimetric testing showed raised thresholds for perception and pain directly after surgery (P = .004-.03), but these were also normalized at the late follow-up.

    CONCLUSION: PBC is a treatment that can be effective for many patients with MS-TN. Repeated previous surgeries is a risk factor for an unsatisfactory outcome. However, the patients with multiple surgeries had less satisfactory results already at the first procedure, indicating that a therapy resistant disease can be predicted after the first two PBCs. Postoperative sensory deficits were common but not lasting.

  • 12.
    Bengtsson, Samuel
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Comorbidity of psychological distress in patients with chronic pain, with focus on burnout, a pilot study2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 13.
    Bergemalm, Daniel
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Mutant superoxide dismutase-1-caused pathogenesis in amyotrophic lateral sclerosis2010Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is a devastating disease that affects people in their late mid-life, with fatal outcome usually within a few years. The progressive degeneration of neurons responsible for muscle movement (motor neurons) throughout the central nervous system (CNS) leads to muscle wasting and paralysis, and eventually affects respiratory function. Most cases have no familial background (sporadic) whereas about 10% of cases have relatives affected by the disease. A substantial number of familial cases are caused by mutations in the gene encoding superoxide dismutase-1 (SOD1). Since the initial discovery of this relationship about 17 years ago, numerous workers have tried to identify the pathogenicity of mutant SOD1 but without any final agreement or consensus regarding mechanism. The experiments in this thesis have been aimed at finding common pathogenic mechanisms by analyzing transgenic mouse models expressing mutant SOD1s with widely different properties.

        Mitochondrial pathology and dysfunction have been reported in both ALS patients and murine models. We used density gradient ultracentrifugation for comparison of mitochondrial partitioning of SOD1 in our transgenic models. It was found that models with high levels of mutant protein, overloaded mitochondria with high levels of SOD1-protein whereas models with wild type-like levels of mutant protein did not. No significant association of the truncation mutant G127X with mitochondria was found. Thus, if mitochondrial dysfunction and pathology are fundamental for ALS pathogenesis this is unlikely to be caused by physical association of mutant SOD1 with mitochondria.

        Density gradient ultracentrifugation was used to study SOD1 inclusions in tissues from an ALS patient with a mutant SOD1 (G127X). We found large amounts in the ventral horns of the spinal cord but also in the liver and kidney, although at lower levels. This showed that such signs of the disease can also be found outside the CNS.

        This method was used further to characterize SOD1 inclusions with regard to the properties of mutant SOD1 and the presence of other proteins. The inclusions were found to be complex detergent-sensitive structures with mutant SOD1 reduced at disulfide C57-C146 being the major inclusion protein, constituting at least 50% of the protein content. Ten co-aggregating proteins were isolated, some of which were already known to be present in cellular inclusions. Of great interest was the presence of several proteins that normally reside in the endoplasmic reticulum (ER), which is in accordance with recent data suggesting that the unfolded protein response (UPR) has a role in ALS.

        To obtain unbiased information on the pathogenesis of mutant SOD1, we performed a total proteome study on spinal cords from ALS transgenic mice. By multivariate analysis of the 1,800 protein spots detected, 420 (23%) were found to significantly contribute to the difference between transgenic and control mice. From 53 proteins finally identified, we found pathways such as mitochondrial function, oxidative stress, and protein degradation to be affected by the disease. We also identified a previously uncharacterized covalent SOD1 dimer.

       In conclusion, the work described in this thesis suggests that mutant SOD1 affects the function of mitochondria, but not mainly through direct accumulation of SOD1 protein. It also suggests that SOD1 inclusions, present in both the CNS and peripheral tissues, mainly consist of SOD1 but they also trap proteins involved in the UPR. This might be deleterious as motor neurons, unable to renew themselves, are dependent on proper protein folding and degradation.

  • 14.
    Bergemalm, Daniel
    et al.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Forsberg, Karin
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Srivastava, Vaibhav
    Sveriges lantbruksuniversitet.
    Graffmo, Karin S.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Andersen, Peter M.
    Umeå universitet, Medicinsk fakultet, Farmakologi och klinisk neurovetenskap, Neurologi.
    Brännström, Thomas
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Wingsle, Gunnar
    Sveriges lantbruksuniversitet.
    Marklund, Stefan L.
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Klinisk kemi.
    Superoxide dismutase-1 and other proteins in inclusions from transgenic amyotrophic lateral sclerosis model miceManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Mutant superoxide dismutase-1 (SOD1) causes amyotrophic lateral sclerosis (ALS) through a cytotoxic mechanism of unknown nature. A hallmark in ALS patients and transgenic mouse models carrying human SOD1 (hSOD1) mutations are hSOD1-immunoreactive inclusions in spinal cord ventral horns. The hSOD1 inclusions may block essential cellular functions or cause toxicity through sequestering of other proteins. Inclusions from 4 different transgenic mouse models were examined after density gradient ultracentrifugation. The inclusions are complex structures with heterogeneous densities and are disrupted by detergents. The aggregated hSOD1 was mainly composed of subunits that lacked the native stabilizing intrasubunit disulfide bond. A proportion of subunits formed hSOD1 oligomers or was bound to other proteins through disulfide bonds. Dense inclusions could be isolated and the protein composition was analyzed using proteomic techniques. Mutant hSOD1 accounted for half of the protein. Ten other proteins were identified. Two were cytoplasmic chaperones, 4 were cytoskeletal proteins, and 4 were proteins that normally reside in the endoplasmic reticulum (ER). The presence of ER proteins in inclusions containing the primarily cytosolic hSOD1 further supports the notion that ER stress is involved in ALS.

  • 15.
    Bergman, Frida
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mattson-Frost, Tove
    Jonasson, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Chorell, Elin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sörlin, Ann
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Fysioterapi.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Öhberg, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Ryberg, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Levine, James
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR).
    Installing treadmill workstations in offices does little for cognitive performance and brain structure, despite a baseline association between sitting time and hippocampus volumeManuskript (preprint) (Övrigt vetenskapligt)
  • 16.
    Björklund, Nikolina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Physical activity, sedentary behaviour and quality of life - the Northern Sweden MONICA Study 20142017Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 17.
    Blad, Nathalie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Does prediagnostic feacal calprotectin associate to tumor characteristics in patients with colorectal cancer?2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 18.
    Blomfeldt, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Medical students’ views on and attitude towards prevention and health promotion in health care2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 19.
    Bobacken, Linn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Logopedi.
    Carlin, Cornelia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Logopedi.
    Kvalitativ utvärdering av steg IV i Swe-LARSP2017Självständigt arbete på avancerad nivå (magisterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Bakgrund: Language Assessment, Remediation and Screening Procedure, LARSP, är ett kliniskt verktyg för att utföra grammatiska analyser av spontantal hos barn med språkliga svårigheter. Än så länge finns inget normerat och standardiserat verktyg för bedömning av spontantal inom svensk logopedisk verksamhet, men en första anpassning av LARSP-protokollet har nyligen gjorts till svenska, Swe-LARSP (Rosenberg & Mellenius, 2016). Swe-LARSP bygger på tidigare empirisk forskning kring typisk språkutveckling hos svenskspråkiga barn, men har ännu inte utvärderats och testats mot spontantal hos svenska barn.

    Syfte: Denna studies syfte var att kvalitativt utvärdera steg IV i Swe-LARSP samt att praktiskt utvärdera användandet av Swe-LARSP.

    Metod: Spontantalsdata samlades in genom inspelningar av 8 normalspråkiga barn i åldern 2;5–3;0 år på fyra olika förskolor i Umeå kommun. Materialet transkriberades och genomgick en grammatisk analys enligt riktlinjer för LARSP. Vidare jämfördes strukturerna i Swe-LARSP-protokollet mot strukturerna som framkom i barnens yttranden.

    Resultat: Resultatet av den grammatiska analysen visade på sju frekvent förekommande strukturer som inte finns placerade i Swe-LARSP samt fyra redan befintliga strukturer med låg förekomst bland barnen. Resterande strukturer på steg IV yttrades av en majoritet av barnen. En struktur, placerad i steg V, förekom även hos en majoritet av barnen i studien.

    Slutsatser: LARSP är ett tidskrävande verktyg och kräver relativt djupgående förkunskaper, men ger en tydlig profil över barnets grammatiska förmåga. Strukturerna i steg IV i Swe-LARSP, som första anpassning, stämmer överens med barnens språk till stor del. Studien har visat att ytterligare strukturer kan behöva läggas till och några av de befintliga tas bort, alternativt placeras om i det befintliga protokollet för att bättre ringa in centrala grammatiska drag i språket hos svenska barn i åldern 2;6–3;0 år.

  • 20.
    Bryntesson, Tobias
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Does electrical neurostimulation of the dorsal root ganglia for pain reduction also influence the perceived temperature detection thresholds? - A pilot study2017Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 21.
    Carlson, Linnéa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Logopedi.
    Upplevda tal- och sångröstproblem: - en jämförelse mellan blivande musikalartister och amatörsångare2018Självständigt arbete på avancerad nivå (magisterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Sammanfattning

    Bakgrund

    Musikal är dans, teater och sång integrerat. De röstkrav musikalartisten har får anses exceptionellt höga. Nästan oavsett rösthälsa förväntas musikalartisten prestera under långa föreställningar med krav på röstkvalitet där både tal- och sångrösten belastas. Musikalakademien i Umeå är en treårig folkhögskoleutbildning med ambitionen att skapa förutsättningar för studenterna att möta de hårda krav som kommer att ställas i yrkeslivet. Detta till trots har både yrkesprofessionella och blivande musikalartister en högre förekomst av röstproblem jämfört med flera andra yrkesgrupper. 

    Syfte

    Föreliggande studie syftade till att undersöka musikalstudenters upplevelse av sin tal- och sångröst i jämförelse med amatörsångares upplevelser av sin röst. Utöver detta avsåg även studien att bidra med kunskap om användbarheten av RHI och RHI-s för respektive grupp.

    Metod

    Studien hade två deltagargrupper; interventionsgruppen vilken bestod av tretton musikalstudenter (7 kvinnor, 6 män) från Musikalakademien i Umeå och kontrollgruppen vilken utgjordes av 13 amatörsångare (10 kvinnor, 3 män) från körer i Umeå och Linköping. Samtliga deltagare bedömde sin röst utifrån validerade självskattningsformulär för talröst (RHI) och sångröst (RHI-s). Utfallen studerades och jämfördes på grupp- och individnivå.

    Resultat

    Samtliga deltagare upplevde större problem med sångrösten än talrösten. Amatörsångarna upplevde mer tal- och sångröstproblem än musikalartisterna.

    Slutsatser

    Studien visade att skolade musikalstudenter upplever lägre grad av röstproblem i jämförelse med oskolade amatörsångare. Sångröstproblem förekom i högre utsträckning än talröstproblem hos båda grupperna. Det validerade självskattningsformuläret RHI-s (för sångröst) bör användas för att studera professionella sångare. Det likvärdiga formuläret RHI (för talröst) är att föredra vid klinisk röstbedömning av amatörsångare.

  • 22.
    Dahlgren, Karl
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Effects of hyperinsulinemia on plasma amyloid beta 42 in patients with type-2 diabetes2015Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 23.
    Danielsson Meiling, Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Risk factors for delirium and mortality in old people after hip fracture2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 24.
    Danielsson, Nora
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Understanding the epidemiology and basic characteristics of hereditary transthyretin amyloidosis in Sweden2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 25. Dorfmeister, B
    et al.
    Zeng, W W
    Dichlberger, A
    Nilsson, Stefan K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Schaap, F G
    Hubacek, J A
    Merkel, M
    Cooper, J A
    Lookene, Aivar
    Putt, W
    Whittall, R
    Lee, P J
    Lins, L
    Delsaux, N
    Nierman, M
    Kuivenhoven, J A
    Kastelein, J J P
    Vrablik, M
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Schneider, W J
    Heeren, J
    Humphries, S E
    Talmud, P J
    Effects of six APOA5 variants, identified in patients with severe hypertriglyceridemia, on in vitro lipoprotein lipase activity and receptor binding2008Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 28, nr 10, s. 1866-1871Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The purpose of this study was to identify rare APOA5 variants in 130 severe hypertriglyceridemic patients by sequencing, and to test their functionality, since no patient recall was possible.

    METHODS AND RESULTS: We studied the impact in vitro on LPL activity and receptor binding of 3 novel heterozygous variants, apoAV-E255G, -G271C, and -H321L, together with the previously reported -G185C, -Q139X, -Q148X, and a novel construct -Delta139 to 147. Using VLDL as a TG-source, compared to wild type, apoAV-G255, -L321 and -C185 showed reduced LPL activation (-25% [P=0.005], -36% [P<0.0001], and -23% [P=0.02]), respectively). ApoAV-C271, -X139, -X148, and Delta139 to 147 had little affect on LPL activity, but apoAV-X139, -X148, and -C271 showed no binding to LDL-family receptors, LR8 or LRP1. Although the G271C proband carried no LPL and APOC2 mutations, the H321L carrier was heterozygous for LPL P207L. The E255G carrier was homozygous for LPL W86G, yet only experienced severe hypertriglyceridemia when pregnant.

    CONCLUSIONS: The in vitro determined function of these apoAV variants only partly explains the high TG levels seen in carriers. Their occurrence in the homozygous state, coinheritance of LPL variants or common APOA5 TG-raising variant in trans, appears to be essential for their phenotypic expression.

  • 26.
    Edin, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Could a specific feature of calcification at the carotid arteries on panorama radiography predict future risk of myocardial infarction or cardiovascular death?2017Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 27.
    Ejnestrand, Jennifer
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Are Swedish swingers a risk group for sexually transmitted infections?2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 28.
    Emdin, Stefan O.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi. Department of Pathology, University of Lund, Malmö General Hospital, Sweden.
    Myxine insulin: amino-acid sequence, three dimensional structure, biosynthesis, release, physiological role, receptor binding affinity, and biological activity1981Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The Atlantic hagfish, Myxlne. glutinosa,is the most primitive vertebrate extant, and it diverged from the main vertebrate evolutionary chain some 500 mi 11 ion years ago.

    The primary sequence of hagfish insulin shows that it contains the residues implemented for expression of activity and the residues stabi­lizing the insulin monomer and dimer, but not the hexamer. The primary sequence of hagfish preproinsulin, deduced from the mRNA-cDNA sequence shows little homology in sequence of the precursor parts of the molecule. However, the sequence contains the structural requirements for the tenta­tive functions, jL.z. vectorial discharge of the prohormone and a minimum over-all size of the precursor. The proinsulin converting enzyme(s) seems to have a specificity similar to that of all other vertebrates studied. The tertiary structure of hagfish insulin in the crystal is almost super­imposable on pig insulin's structure.

    The biological  activity of hagfish insulin is 5%   of that  of piginsulin and its receptor binding affinity   is 23% in isolated   rat fat  cells.Hagfish insulin was the first partial insulin antagonist on the rat fat cell insulin receptor. The change(s) in structure responsible for the reduction of acti­vity and binding are not known.

    Biosynthesis of hagfish insulin, In vXJyto, follows the pattern observed in higher vertebrates, although at a much slower rate. Unlike the situation in mammals, hagfish insulin biosynthesis is not stimulated by glucose.

    A radioimmunoassay for hagfish insulin was developed and the antiserum cross-reacted with       bovine insulin to only 0.01%. Theassay was used to study insulin release in vitro. Glucose  stimulates insulin release but, unlike the situation in higher vertebrates, amino acids do not.

    In vivo, hagfish insulin stimulated the incorporation of 14C-glucose and 14C-leucine into hagfish skeletal muscle glycogen and protein.

    The observed similari ties,between hagfish and higher vertebrates,with regards to insulin's structure, biosynthesis, release, receptor binding, and biological activity support the conclusion that, insulin and its processing and effector machineries were structurally and biologically well defined some 500 million years ago.

  • 29.
    Englund, Claire
    et al.
    Umeå universitet, Umeå universitetsbibliotek (UB), Universitetspedagogik och lärandestöd (UPL).
    Gustafsson, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Gallego, Gisselle
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi. School of Medicine, The University of Notre Dame, Australia, New South Wales 2010, Australia.
    Pharmacy Students' Attitudes and Perceptions of "Virtual Worlds" as an Instructional Tool for Clinical Pharmacy Teaching2017Ingår i: Pharmacy, ISSN 2226-4787, Vol. 5, nr 1, artikel-id 5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The objectives of this study were to explore pharmacy students’ perceptions and experiences of three-dimensional virtual worlds (3DVWs) as an instructional tool for clinical pharmacy teaching. Semi-structured interviews were carried out with Master of Science in Pharmacy students who had participated in communicative exercises in a 3DVW. Interviews were digitally recorded, transcribed and analyzed using thematic analysis. More than half of the students were positive to using 3DVWs for educational purposes and see the advantages of having a setting where communication can be practiced in an authentic but ‘safe’ environment available online. However, many students also reported technical difficulties in using the 3DVW which impacted negatively on the learning experience. Perceived ease of use and usefulness of 3DVWs appears to play an important role for students. The students’ level of engagement relates to not only their computer skills, but also to the value they place on 3DVWs as an instructional tool.

  • 30.
    Eriksson Ström, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Increased BALF NK cells associated with COPD, iNKT and NKT-like cells with current smoking2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 31.
    Falk, Hilda
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    How many patients had their colon investigated within five years prior colorectal cancer diagnosis?2017Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 32.
    Forsberg, Ulf
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Jonsson, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Air contamination during medical treatment results in deposits of microemboli in the lungs: an autopsy study2019Ingår i: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 42, nr 9, s. 477-481Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Microbubbles of air may enter into patients during conventional hemodialysis, infusions of fluids, or by injections. The aim of this study was to investigate whether the air that enters the patient during hemodialysis can be detected in the lungs after death, and if so, whether this may be related to tissue damage. Methods: The material consisted of lung tissue from five chronic hemodialysis patients who died either during (two) or after hemodialysis (range 10 min from start until 3333 min after the last hemodialysis session); as reference group tissue was taken from seven patients who died due to amyotrophic lateral sclerosis. The lung tissue was investigated by microscopy after autopsy using a fluorescein-marked polyclonal antibody against fibrinogen as a marker for clots preformed before death. Results: All five hemodialysis patients had microbubbles of air in the lung tissue, whereas two of seven amyotrophic lateral sclerosis patients had such findings (Fisher's test p = 0.0278, relative risk = 3.5, confidence interval: 1.08-11.3). There were more microbubbles of air/10 randomly investigated microscopic fields of tissue in the hemodialysis patients than the amyotrophic lateral sclerosis patients (Student's test, p < 0.05). All hemodialysis patients had a medium graded extent of pulmonary fibrosis that was not found in any of the ALS patients. The microbubbles of air were surrounded by fibrin as a sign of development of clots around the air bubbles while the patients were still alive. Conclusion: Exposure to microbubbles of air during various treatments such as hemodialysis may result in microemboli. Future studies should clarify whether microbubbles of air contribute to tissue scarring. We suggest preventive measures against the exposure to microbubbles of air during especially repeated exposures such as hemodialysis.

  • 33.
    Gaversjö, Malena
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Prevalence of obstetric anal sphincter injury following breech delivery2016Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 34.
    Gouveia-Figueira, Sandra
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Goldin, Kristina
    Hashemian, Sanaz A.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Lindberg, Agneta
    Persson, Monica
    Nording, Malin L.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Laurell, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap. Department of Neurology, Östersund Hospital, SE-83183 Östersund, Sweden.
    Fowler, Christopher J.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Plasma levels of the endocannabinoid anandamide, related N-acylethanolamines and linoleic acid-derived oxylipins in patients with migraine2017Ingår i: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 120, s. 15-24Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is evidence that patients with migraine have deficient levels of the endogenous cannabinoid receptor ligand anandamide (AEA). It is not known, however, if this is a localised or generalised phenomenon. In the present study, levels of AEA, related N-acylethanolamines (NAEs) and linoleic acid-derived oxylipins have been measured in the blood of 26 healthy women and 38 women with migraine (26 with aura, 12 without aura) who were matched for age and body-mass index. Blood samples were taken on two occasions: the first sample near the start of the menstrual cycle (when present) and the second approximately fourteen days later. For a subset of migraine patients, two additional blood samples were taken, one during a migraine attack and one approximately 1 month later (to be at the same stage in the menstrual cycle, when present). NAEs and oxylipins were measured by liquid chromatography coupled to mass spectrometry. Twenty-nine lipids were quantified, of which 16 were found to have a high reproducibility of measurement. There were no significant differences in the levels of AEA, the related NAEs stearoylethanolamide and oleoylethanolamide or any of the nine linoleic acid derived oxylipins measured either between migraine patients with vs. without aura, or between controls and migraine patients (after stratification to take into account whether or not the individuals had regular menstruation cycles) in either of the first two samples. Levels of linoleoylethanolamide were lower in the patients with vs. without aura on the second sample but not in the first sample, but the biological importance of this fording is unclear. Due to time-dependent increases in their concentrations ex vivo prior to centrifugation, AEA and oleoylethanolamide levels in the samples collected during migraine attacks were not analysed, but for the other fourteen lipids, there were no significant differences in plasma concentrations during migraine vs. one month later. It is concluded that migraine is not associated with a generalised (as opposed to localised) deficiency in these lipids.

  • 35.
    Grantén, Malte
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Diagnostic yield of small bowel capsule endoscopy2016Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 36.
    Grollmuss, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Identifying unmet rehabilitation needs in patients after stroke or transient ischemic attack at the sub-acute stage2017Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 37. Gu, Qiang
    et al.
    Kong, Yan
    Schneede, Jörn
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi. Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk farmakologi.
    Xiao, Ying-Bin
    Chen, Lin
    Zhong, Qian-Jin
    Wang, Xue-Feng
    Hao, Jia
    Chen, Bai-Cheng
    Chen, Jing-Jin
    VKORC1-1639G>A, CYP2C9, EPHX1691A>G genotype, body weight, and age are important predictors for warfarin maintenance doses in patients with mechanical heart valve prostheses in southwest China2010Ingår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 66, nr 12, s. 1217-1227Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There were great interindividual differences in warfarin maintenance dosage (ranging from 0.6 to 8.4 mg/day) among the 127 patients with mechanical heart valve prostheses. VKORC1-1639G>A, CYP2C9, EPHX1691A>G polymorphism, body weight, and age were found to affect the dose demands. Multiple linear regression models incorporating genetic polymorphisms of VKORC1, CYP2C9, EPHX1691A>G, and the nongenetic factors of age and body weight were developed, and explained up to 76.8% of the total variation (adjusted R (2) of 0.743) in warfarin maintenance doses in southwest Chinese patients with mechanical heart valve prostheses.

  • 38.
    Gustafsson, Patrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Crenshaw, Albert G.
    Edmundsson, David
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Toolanen, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Crnalic, Sead
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Ortopedi.
    Muscle oxygenation in Type 1 diabetic and non-diabetic patients with and without chronic compartment syndrome2017Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 12, nr 10, artikel-id e0186790Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Type 1 diabetic patients and non-diabetic patients were referred for evaluation for chronic exertional compartment syndrome (CECS) based on clinical examination and complaints of activity-related leg pain in the region of the tibialis anterior muscle. Previous studies using near-infrared spectroscopy (NIRS) showed greater deoxygenation during exercise for CECS patients versus healthy controls; however, this comparison has not been done for diabetic CECS patients. Methods: We used NIRS to test for differences in oxygenation kinetics for Type 1 diabetic patients diagnosed with (CECS-diabetics, n = 9) versus diabetic patients without (CON-diabetics, n = 10) leg anterior chronic exertional compartment syndrome. Comparisons were also made between non-diabetic CECS patients (n = 11) and healthy controls (CON, n = 10). The experimental protocol consisted of thigh arterial cuff occlusion (AO, 1-minute duration), and treadmill running to reproduce symptoms. NIRS variables generated were resting StO(2)%, and oxygen recovery following AO. Also, during and following treadmill running the magnitude of deoxygenation and oxygen recovery, respectively, were determined. Results: There was no difference in resting StO2% between CECS-diabetics (78.2 +/- 12.6%) vs. CON-diabetics (69.1 +/- 20.8%), or between CECS (69.3 +/- 16.2) vs. CON (75.9 +/- 11.2%). However, oxygen recovery following AO was significantly slower for CECS (1.8 +/- 0.8%/sec) vs. CON (3.8 +/- 1.7%/sec) (P = 0.002); these data were not different between the diabetic groups. StO2% during exercise was lower (greater deoxygenation) for CECS-diabetics (6.3 +/- 8.6%) vs. CON-diabetics (40.4 +/- 22.0%), and for CECS (11.3 +/- 16.8%) vs. CON (34.1 +/- 21.2%) (P<0.05 for both). The rate of oxygen recovery post exercise was faster for CECS-diabetics (3.5 +/- 2.6%/sec) vs. CON-diabetics (1.4 +/- 0.8%/sec) (P = 0.04), and there was a tendency of difference for CECS (3.1 +/- 1.4%/sec) vs. CON (1.9 +/- 1.3%/sec) (P = 0.05). Conclusion: The greater deoxygenation during treadmill running for the CECS-diabetics group (vs. CON-diabetics) is in line with previous studies (and with the present study) that compared non-diabetic CECS patients with healthy controls. Our findings could suggest that NIRS may be useful as a diagnostic tool for assessing Type 1 diabetic patients suspected of CECS.

  • 39.
    Gällstedt, Caroline
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Logopedi.
    Larsson, Matilda
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Logopedi.
    Upplevda röstbesvär: Hos lärarstudenter vid Umeå universitet2017Självständigt arbete på avancerad nivå (magisterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [sv]

    Sammanfattning

    Bakgrund

    Läraryrket är röstkrävande och lärare har en högre förekomst av röstbesvär jämfört med andra yrkesgrupper. Röstbesvär har även visats vanliga hos lärarstudenter. På Umeå universitet erbjuds en preventiv behandling för lärarstudenter som är viktig för att förbättra rösthälsan i läraryrket.

    Syfte

    Denna studie syftar till att undersöka förekomst av upplevda röstbesvär hos lärarstudenter vid Umeå universitet. Vi vill bidra med information om faktorer som kan påverka studenternas upplevda röstbesvär samt utveckla den preventiva behandlingsinsats som finns i dagsläget.

    Metod

    Autentisk data från lärarstudenter vid Umeå universitet har samlats in under 20 år i samband med ett förebyggande röstmoment i lärarutbildningen. Genom en databasforskning och en enkätundersökning för röstlogopeder i Västerbotten har upplevda röstbesvär och faktorer som kan påverka dessa undersökts.

    Resultat

    Aktuell studie har visat att av alla deltagande lärarstudenter under en 10-årsperiod var det 18,4% som upplevde röstbesvär. Det vanligaste symtomet bland studenterna var ansträngd eller trött röst. När inverkan på studenternas upplevda röstbesvär undersöktes i samband med verksamhetsförlagd utbildning syntes en signifikant ökning av upplevda röstbesvär hos hela gruppen. Röstlogopederna ansåg att röstbelastning var en betydande faktor gällande individers medvetna röstbesvär. Röstkrävande fritidsaktiviteter var även den enda protokollfaktor som var procentuellt högre hos studenter med upplevda röstbesvär.

    Slutsats

    Resultatet av denna studie har visat att verksamhetsförlagd utbildning har en inverkan på upplevda röstbesvär och styrker även tidigare teorier om detta. Aktuell studie vill därmed belysa vikten av den preventiva behandlingens placering då den med fördel bör ske i samband med att studenterna ökar sin röstbelastning under VFU-perioderna.

  • 40.
    Hedenskog, Pelle
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Prognostic importance of the position of the head in diagnostic CT scan in stroke patients.2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 41.
    Heldestad, Victoria
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurofysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Methodological aspects and usefulness of Quantitative Sensory Testing in early small fiber polyneuropathy: a clinical study in Swedish hereditary transthyretin amyloidosis patients2011Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Generalised polyneuropathy (PNP) is a common cause to neurological impairment, and may be an early symptom of a severe systemic disease. One such illness is hereditary transthyretin (TTR) amyloidosis (ATTR), a progressive fatal disorder caused by a mutation on the TTR gene. More than 100 such mutations have been found worldwide, of which Val30Met is the most common neuropathic variant with initial clinical manifestations indicating small fiber impairment. Differences in onset age, penetrance and phenotypes are present between endemic areas. Liver transplantation generally slows the progress of the symptom development, especially in patients with short disease duration. Ongoing research has also shown promising results with drug interventions. In any event, early diagnosis of PNP onset in ATTR patients is crucial to ensure early therapeutic interventions. Nerve conduction studies (NCS) and electromyography (EMG) provide the basis for evaluation of the functional state of the thick myelinated nerve fibres in patients with symptoms of PNP, but no such quantitative methods are available for the thin myelinated or unmyelinated fibers. Instead, a psychophysical method with thermal quantitative sensory testing (QST) can provide indirect information about the overall function in the afferent small fiber systems. The purpose of thesis was to evaluate the applicability of QST by the Method-of-limits (MLI) for early detection of PNP in Swedish ATTR patients with the Val30Met mutation.

    In healthy subjects the repeatability of the MLI was assessed, and reference values for thermal perception thresholds (TPT) in several body regions were determined. No significant differences in TPT or pain thresholds were found at repeated testing with MLI, indicating that the MLI is a reliable method. However, the results show that the arrangement of the testing order is of importance, as cold (CT) and warm (WT) perception thresholds were significantly elevated when tested after thermal pain assessments, instead of before. I general, the TPT was more elevated at lower parts of the body compared to the upper part, and with higher WT than CT, fully in accordance with the underlying anatomical and physiological prerequisites for QST. In biopsy verified ATTR patients lacking EMG and NCS abnormalities, significantly elevated TPT were found compared to controls. Furthermore, significantly more increased TPT were observed in patients with an early onset of the disease, compared those with a late onset. Finally, a combined detailed evaluation of QST and heart rate variability (HRV) analyses demonstrated correlations between QST and HRV abnormalities in patients with late onset, but not in those with early onset.

    The present thesis emphasizes the importance of incorporating QST early in the clinical evaluation of ATTR patients with a Val30Met mutation and with symptoms of thin fiber PNP. This is particularly indicated when patients report symptoms, or show signs, of neuropathic small fiber affection, but simultaneously exhibit normal EMG and NCS findings. The results furthermore underline the importance of performing both QST and HRV for a complete evaluation of both the thin somatic and autonomic nerve fibers, as both types of nerves may be affected early in the ATTR disease.

  • 42.
    Henein, Michael Y.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Suhr, Ole B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Arvidsson, Sandra
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Pilebro, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Westermark, Per
    Hörnsten, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis2018Ingår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, nr 1, s. 46-53Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Cardiac amyloidosis (CA) is a myocardial disease and commonly under-diagnosed condition. In CA patients, atrial fibrillation might occur in the absence of left atrial (LA) enlargement.

    OBJECTIVES: The aim of this study is to assess LA size and function, and its relationship with atrial arrhythmia in patients with hereditary transthyretin amyloidosis (ATTR).

    METHODS: Forty-six patients with confirmed ATTR amyloidosis on abdominal biopsy were studied. Assessment with 2D echocardiography and 2D strain showed 31 patients had increased LV wall thickness (LVWT) (septal thickness >12 mm), and 15 had normal LVWT. In addition to conventional measurements, LV and LA global longitudinal strain (GLS%) and strain rate (SR) were obtained. Western blot analysis was done to assess fibril type. ATTR patients with increased LVWT were compared with 23 patients with hypertrophic cardiomyopathy (HCM) and 31 healthy controls. ATTR amyloidosis patients also underwent 24 hour Holter monitoring to determine the presence of atrial arrhythmia.

    RESULTS: Atrial deformation during atrial systole was reduced in ATTR amyloidosis patients with increased LVWT independent of LA size and in contrast to HCM. Twenty of the ATTR amyloidosis patients (54%) had ECG evidence of significant atrial arrhythmic events. LA strain rate, during atrial systole, was the only independent predictor of atrial arrhythmia (β = 3.28, p = .012).

    CONCLUSION: In ATTR cardiomyopathy with increased LVWT, LA myocardial function is abnormal, irrespective of atrial cavity size. Reduced LA myocardial SR during atrial systole, irrespective of cavity volume, E/e' and LV deformation, is also a strong predictor for atrial arrhythmic events.

  • 43.
    Hovstadius, Henrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Do patients with elevated fecal calprotectin levels but normal colonoscopy develop significant gastrointestinal disease? - A prospective study.2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 44.
    Imamović, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    The Effect of Licorice on Late-night Salivary Cortisol2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 45.
    Ingermarsson, Johanna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Leptin levels – as a risk factor for cardiovascular disease A study based on the Northern Sweden MONICA Project2017Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 46.
    Jallow, Tim
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Diurnal, weekly, and seasonal variation in out-of-hospital cardiac arrest in northern Sweden - A MONICA Myocardial Infarction Registry study2016Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 47.
    Janson, Veronica
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap.
    Cisplatin-resistance and cell death in malignant pleural mesothelioma cells2008Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Malignant pleural mesothelioma (MPM) is an aggressive, treatment-resistant tumour. Cisplatin (cis-diamminedichloroplatinum (II)) is the best single-agent chemotherapy for MPM, but platinum-based combination therapies give the best overall response rates. However, cisplatin use is limited by resistance and severe side effects. This thesis has increased the knowledge concerning cisplatin-induced cell death in MPM by describing a novel potential therapeutic target, and three novel phenotypes of cisplatin-resistance in a human MPM cell line (P31) and its cisplatin-resistant sub-line (P31res1.2).

    The novel potential therapeutic target, and one of the novel phenotypes, was cisplatin-resistant pro-apoptotic BH3-only proteins. In the P31 cells, cisplatin transiently increased pro-apoptotic BH3-only proteins during 6 h of exposure. This response was almost completely abrogated in the P31res1.2 cells. De-regulated caspase activity and activation was the second novel phenotype identified. The P31res1.2 cells had earlier, possibly mitochondria-independent, caspase-3 activation, increased basal caspase-3 activity and increased basal cleavage of caspase-8 and -9. Despite these differences, 6-h equitoxic cisplatin exposures rendered 50-60% of the cells apoptotic in both cell lines. The third novel phenotype was abrogated Na+K+2Cl--cotransporter (NKCC1) activity. Although NKCC1 activity was dispensable for cisplatin-induced apoptosis, balanced potassium transport activity was essential for P31 cell survival. Finally, the survival signalling protein Protein Kinase B (PKB or Akt) isoforms α and γ were constitutively activated in a PI3K-independent manner in P31 cells. In the P31res1.2 cells, PKBα and γ activities were increased, and there was PI3K-dependent activation of PKBβ. However, this increase in PKB isoform activity was not strongly associated to the cisplatin-resistance of the P31res1.2 cells.

  • 48.
    Johansson, David
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap.
    Bacterial toxins for cancer treatment2008Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Even though anti‐cancer chemotherapy has been continuously improved during the last decades. problems with adverse effects and drug resistance still constitutes a considerable obstacle and sets a demand for new effective treatment options. Tissue homeostasis in multi‐cellular organisms is maintained through intrinsic cell death, apoptosis, which removes unwanted or damaged cells. Disrupted apoptosis is an important factor in tumorgenesis and drug resistance, therefore induction or restoration of apoptotic pathways is also important for the treatment of cancer. Several naturally occurring bacterial toxins have the ability to induce apoptosis and could thus be candidates to complement or improve the therapeutic effect of other anticancer drugs.

    The bacterial toxins, adenylate cyclase (AC) toxin from Bordetella pertussis, α‐toxin from Staphylococcus aureus and verotoxin‐1 (VT‐1) from Escherichia coli were investigated for their ability to induce apoptosis in different tumor cell lines. Toxin induction of cell death was investigated by cell viability assays, end‐stage apoptosis induction by DNA‐fregmentation (TUNEL) assay. Toxin receptor expression and signal transduction pathways to apoptosis were investigated by flow cytometry, caspase enzyme activity assays and western blot. Immunohistochemistry was used for identification of toxin receptor expression in tumor tissue samples.

    AC‐toxin was cytotoxic and induced apoptosis in cultured malignant plural mesothelioma (MPM) and small‐cell lung cancer (SCLC) cells. Low‐toxic concentrations of AC‐toxin enhanced cisplatin cytotoxicity and apoptosis in both cell lines.

    MPM‐cells with acquired cisplatin resistance were more sensitive to α‐toxin than the less resistant parental MPM cell line. A low‐toxic concentration of α‐toxin re‐sensitized resistant MPM cells to cisplatin cytotoxicity by apoptosis induced through the mitochondrial pathway without detectable activation of common up‐stream apoptosis signalling proteins.

    VT‐1 was highly cytotoxic and induced apoptosis in globotriosylceramide (Gb3) ‐expressing glioma, breast cancer and non‐small‐cell lung cancer (NSCLC) cells but was not cytotoxic to non‐Gb3‐expressing cells. PPMP, an inhibitor of glucosylceramide synthesis which makes exposed cells unable to synthesize Gb3 rendered Gb3‐expressing cells resistant to VT‐1. MPM cells with acquired‐cisplatin resistance expressed Gb3 in contrast to the absent of expression in the less resistant parental cell line. Gb3, could however be up‐regulated by cisplatin in Gb3‐negative MPM‐cells. Presence of a low‐toxic concentration of VT‐1 potentiated cisplatin‐induced cytotoxicity and apoptosis in the cisplatin‐resistance MPM cell line. VT‐1 was a potent inducer of apoptosis, probably via stress‐induced Mitogen‐activated protein kinase (MAPK)‐signaling involving c‐Jun N‐terminal kinase (JNK) and p38, leading to disruption of the mitochondrial membrane integrety, activation of caspase‐9 and ‐3, and ultimately DNA fragmentation and cell death. Gb3 expression was demonstrated in clinical specimens of glioblastoma and breast cancer making these tumor types interesting for further VT‐1 studies.

    We conclude that bacterial toxins may be used to induce apoptosis in several types of cancer cells. Low concentrations of verotoxin‐1 and α‐toxin may potentially be used to overcome acquired cisplatin‐resistance in cancer patients.

  • 49.
    Johansson, Elias
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Carotid stenosis2011Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Carotid stenosis is one of several causes of ischemic stroke and entails a high risk of ischemic stroke recurrence. Removal of a carotid stenosis by carotid endarterectomy results in a risk reduction for ischemic stroke, but the magnitude of risk reduction depends on several factors. If the delay between the last symptom and carotid endarterectomy is less than 2 weeks, the absolute risk reduction is >10%, regardless of age, sex, or if the degree of carotid stenosis is 50–69% or 70–99%. Thus, speed is the key. However, if many patients suffers an ischemic stroke recurrence within the first 2 weeks of the presenting event, an additional benefit is likely be obtained if carotid endarterectomy is performed even earlier than within 2 week after the presenting event.

    Carotid endarterectomy for asymptomatic carotid stenoses carries a small risk reduction for stroke. Screening for asymptomatic carotid stenosis requires a prevalence of >5% in the examined population, i.e., higher than in the general population; however, directed screening in groups with a prevalence of >5% is beneficial.

    The aims of this thesis were to investigate the length of the delay to carotid endarterectomy, determine the risk of recurrent stroke before carotid endarterectomy, and determine if a calcification in the area of the carotid arteries seen on dental panoramic radiographs is a valid selection method for directed ultrasound screening to detect asymptomatic carotid stenosis.

    Consecutive patients with a symptomatic carotid stenosis who underwent a preoperative evaluation aimed at carotid endarterectomy at Umeå Stroke Centre between January 1, 2004–March 31, 2006 (n=275) were collected retrospectively and between August 1, 2007–December 31, 2009 (n=230) prospectively. In addition, 117 consecutive persons, all preliminarily eligible for asymptomatic carotid endarterectomy and with a calcification in the area of the carotid arteries seen on panoramic radiographs, were prospectively examined with carotid ultrasound.

    The median delay between the presenting event and carotid endarterectomy was 11.7 weeks in the first half year of 2004, dropped to 6.9 weeks in the first quarter year of 2006, and had dropped to 3.6 weeks in the second half year of 2009.

    The risk of ipsilateral ischemic stroke recurrence was 4.8% within 2 days, 7.9% within 1 week, and 11.2% within 2 weeks of the presenting event. For patients with a stroke or transient ischemic attack as the presenting event, this risk was 6.0% within 2 days, 9.7% within 1 week, and 14.3% within 2 weeks of the presenting event. For the 10 patients with a near-occlusion, the risk of ipsilateral ischemic stroke recurrence was 50% at 4 weeks after the presenting event.

    Among the 117 persons with a calcification in the area of the carotid arteries seen on panoramic radiographs, eight had a 50–99% carotid stenosis, equalling a prevalence of 6.8% (not statistically significantly over the pre-specified 5% threshold). Among men, the prevalence of 50–99% carotid stenosis was 12.5%, which was statistically significantly over the pre-specified 5% threshold.

    In conclusion: The delay to carotid endarterectomy was longer than 2 weeks. Additional benefit is likely to be gained by performing carotid endarterectomy within a few days of the presenting event instead of at 2 weeks because many patients suffer a stroke recurrence within a few days; speed is indeed the key. The finding that near-occlusion entails an early high risk of stroke recurrence stands in sharp contrast to previous studies; one possible explaination is that this was a high-risk period missed in previous studies. The incidental finding of a calcification in the area of the carotid arteries on a panoramic radiograph is a valid indication for carotid ultrasound screening in men who are otherwise eligible for asymptomatic carotid endarterectomy.

  • 50.
    Johansson, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Is Celiac Dietary Adherence Test useful in Sweden as a follow-up method of patients with Celiac Disease2018Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
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