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1.
  • Hultin Jäderlund, Karin, et al. (författare)
  • Cerebrospinal Fluid PCR and Antibody Concentrations against Anaplasma phagocytophilum and Borrelia burgdorferi sensu lato in Dogs with Neurological Signs
  • 2009
  • Ingår i: Journal of Veterinary Internal Medicine. - : Wiley. - 0891-6640 .- 1939-1676. ; 23, s. 669-672
  • Tidskriftsartikel (refereegranskat)abstract
    • The tick-borne bacteria Borrelia burgdorferi sensu lato (sl) and Anaplasma phagocytophilum have been suspected to cause neurological signs in dogs. Diagnosis often has been made based on positive antibody titers in serum of dogs with neurological signs, but a high seroprevalence in dogs in at-risk populations makes diagnosis difficult.To determine if the neurological signs in dogs examined were caused by any of these bacteria.Fifty-four dogs presented to a board-certified neurologist.Prospective study. We divided dogs into 2 groups: those with inflammatory diseases of the central nervous system (CNS) and those with neurological signs from other diseases. Blood and cerebrospinal fluid (CSF) from all dogs were analyzed.Dogs with inflammatory CNS diseases showed no serum antibodies against any of the agents. Among dogs with neurological signs from other diseases, 10.3% had serum antibodies for B. burgdorferi sl and 20.5% for A. phagocytophilum. All blood samples analyzed for bacterial deoxyribonucleic acid (DNA) and all CSF analyzed for antibodies and bacterial DNA for the 2 agents were negative.Based on this study, these bacteria are unlikely causes of neurologic disease in dogs and the presence of serum antibodies alone does not document or establish a definitive diagnosis of CNS disease caused by these organisms. Dogs that have neurologic disease and corresponding serum antibodies against these agents should have additional tests performed to assess for other potential etiologies of the signs.
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2.
  • Macias Garcia, B., et al. (författare)
  • Single-Layer Centrifugation Through Colloid Positively Modifies the Sperm Subpopulation Structure of Frozen-Thawed Stallion Spermatozoa
  • 2009
  • Ingår i: Reproduction in domestic animals. - : Wiley-Blackwell. - 0936-6768 .- 1439-0531. ; 44:3, s. 523-526
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study attempted to select the subpopulation of stallion spermatozoa that best survived a conventional freezing and thawing procedure, using centrifugation of post-thawed semen samples through a single layer of a glycidoxypropyltrimethoxysilane-coated silica colloid with a species-specific formulation (Androcoll-E (TM)). After freezing and thawing, four sperm subpopulations were identified, listed as FT1 to FT4. While subpopulations FT1 and FT2 were characterized by low sperm velocity, high velocities characterized the ones called FT3 and FT4. The single-layer centrifugation (SLC)-handled sperm sample was enriched in subpopulation FT3, reaching a proportion of 82.6% of the present spermatozoa, in contrast with the non-filtered control post-thawed semen, where this sperm subpopulation only accounted for 16.3% of the total. It is concluded that in the equine industry, the SLC is a practical, easy-to-perform approach to improve the quality of equine frozen-thawed semen samples.
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4.
  • Löfgren, Magnus, 1979- (författare)
  • Behavioral effects of female sex steroid hormones : models of PMS and PMDD in Wistar rats
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background Animal models can be used to mimic human conditions of psychopathology, and also as pre-clinical models to evaluate candidate drugs. With hormonal treatment it is possible to produce behavior in the rat which corresponds to the mental symptoms of pre-menstrual syndrome (PMS), and pre-menstrual dysphoric disorder (PMDD). PMS affects 25-30 % of all women in fertile age and 3-8% are diagnosed with the more severe condition PMDD. The cardinal mental symptoms are; irritability, mood-swings, depression, anxiety, fatigue, insomnia, difficulties with concentration and memory and learning difficulties. The symptoms of PMS/PMDD occur in the luteal phase in conjunction with increasing concentrations of progesterone (P4) and P4-metabolites. In anovulatory cycles the symptoms are absent. The hormones which produce the monthly reoccurring negative symptoms on mood are foremost the neuroactive metabolites; allopregnanolone (ALLO) and tetrahydro-deoxycorticosterone (THDOC). ALLO is produced by the corpus luteum, but can also be synthesized in the brain, both ALLO and THDOC can also be released from the adrenal cortex during stress. These steroids are active on the inhibitory GABA neurotransmitter system through the GABAA receptor, and the effects are similar to that of alcohol and benzodiazepines. These steroids have strong sedative and hypnotic effects. A paradox is that some individuals seem to react with negative mood on sex steroids while all fertile women have the cyclical steroid changes during the menstrual cycle. Some individuals are more sensitive to neuroactive steroids with influences of personality, heritability and stress factors. Aims The thesis aims were to develop pre-clinical animal models of PMS/PMDD and to investigate induction of ALLO tolerance, individual sensitivity to neurosteroids and the interactions between chronic social stress and neurosteroids. Methods In these studies male and female Wistar rats were used to test steroid hormone effects on learning and memory and behaviors analogous to negative mood symptoms. This was accomplished through hormonal treatment and a subsequent withdrawal period from P4 (P4) + estradiol (E2) (PEWD), or ALLO. To assess tolerance, memory and learning in the Morris water maze (MWM) was studied. Anxiety-like behaviors were tested with the elevated plus maze (EPM), open field test (OFT), and the intruder test (IT). The EPM or OFT was used to classify the rats as high or low responders on risk-taking and explorative behavior (HR/LR). For social ranking order assessment the tube test (TT) and food competition test (FCT) were used. Chronic social stress was accomplished through co-habituation with two older rats (chronic subordination stress). In female rats the estrous cycle followed using staining of vaginal smears. Concentration of corticosterone (CORT) was measured by radio-immuno-assay (RIA). Results In the MWM ALLO pre-treatment produced tolerance to the acute negative ALLO effects. Both male and female rats showed behavioral correlations between the EPM and OFT tests, and correlations were also seen in CORT levels. Individuals with the stable trait of high risk-taking and explorative behavior (HR) were more sensitive to PEWD induction of anxiety-like behavior. These animals also showed decreased CORT levels during withdrawal. Chronic subordination stress enhanced the response to PEWD on measures of locomotor activity and social anxiety-like behavior. Conclusions It is possible to induce tolerance to the negative ALLO effects on learning and memory. The animal models of anxiety-like behavior show an individual PEWD response profile where HR rats are more sensitive. Exposure to chronic social stress enhanced the PEWD response. Hence there are both inherent and environmental factors behind the behavioral response to steroid hormones in rats.
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5.
  • Wanby, Pär (författare)
  • On certain genetic and metabolic risk factors for carotid stenosis and stroke
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The present study evaluated genetic and metabolic factors influencing the risk of acute cerebrovascular disease (CVD) and internal carotid artery stenosis (ICA stenosis) in a Swedish community. The threonine (T) containing protein of the FABP2 A54T gene polymorphism has a greater affinity for long chain fatty acids (FFAs) than the alanine (A) containing protein. This altered affinity for FFAs has been shown to affect the intestinal absorption of fatty acids and consequently the fatty acid composition of serum lipids, in particularly postprandially. Endothelium derived NO is a potent vasodilator and antiatherogenic agent. Asymmetric dimethyl arginine (ADMA) is an endogenous competitive inhibitor of endothelial nitric oxide synthase (eNOS). ADMA has been shown to be involved in the pathogenesis of atherosclerotic disease, and ADMA inhibits eNOS by displacement of L-arginine from the enzyme, which in turn is believed to affect the amount of NO available within the endothelium.The FABP2 A54T gene polymorphism was analyzed in 407 patients with acute CVD and also in a subset of these patients whose carotids had been evaluated with ultrasound. Both the FABP2 polymorphism and a common polymorphism of the eNOS gene, Glu298Asp, were analyzed in a different population consisting of 54 matched pairs of patients with ICA stenosis and controls. ADMA levels were measured in both study populations.We found that the T54 allele was more frequent in patients with transient ischaemic attacks (TIA), and that the TT genotype was more prevalent in young, non-smoking patients with CVD than in controls.Increased concentrations of ADMA were observed in cardio-embolic infarction and TIA, but not significantly in non-cardio-embolic infarction nor in haemorrhagic stroke. In multivariate logistic regression models, CVD increased across quartiles of ADMA in all subgroups, but this association was only significant in the TIA group. A decreased arginine/ADMA ratio, a measure of NO availability was associated with CVD in the entire study population. Patients with severe carotid stenosis had significantly higher ADMA levels than the controls. Allele and genotype frequencies of the FABP2 and eNOS polymorphisms did not differ between patients with ICA stenosis and controls.Our results indicate that ADMA is a strong marker for TIA and severe ICA stenosis, and that relative defiency of arginine, measured as L-arginine/ADMA, is present in acute CVD.We also conclude that a common polymorphism of the FABP2 gene increases susceptibility to ischaemic stroke and TIA.
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6.
  • Andersson, Gunnel, 1958- (författare)
  • Urinary incontinence : prevalence, treatment seeking behaviour, experiences, and perceptions among persons with and without urinary leakage
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The overall aim of this thesis is to describe urinary incontinence (UI) from a population perspective and to describe experiences and perceptions of UI from an individual perspective. This includes assessing the prevalence of urinary incontinence as well as describing treatment seeking and experiences of living with UI. A secondary aim was to describe the perception of UI among cultures other than the Swedish mainstream, exemplified in this case by Syrian women living in Sweden. Both quantitative and qualitative methods were used, including questionnaires and interviews. Studies I and II were quantitative studies based on a population-based study. Together with a postal survey on general health and living conditions “Life & Health”, a questionnaire on urinary incontinence was sent out to 15 360 randomly-selected residents aged 18-79 in Orebro County, Sweden. In Study I, UI was found to affect 19%. The majority of the respondents experienced minor problems, and only 18% of those reporting UI wanted treatment. However, there was also a group who reported severe problems, but despite this 42% of them did not want treatment. Study II investigated why people with UI refrain from seeking care and treatment. It was found that the desire for treatment was regulated by the frequency of UI, being restricted from participating in various activities, the degree of inconvenience, and the type of UI. Studies III and IV were both qualitative interview studies, describing older women’s experiences of living with UI (Study III) and Syrian women’s perceptions of UI (Study IV). There were similarities between the results of these two studies; the women described UI as a normal and expected problem, and they knew that the district nurse could prescribe incontinence protections and that treatments existed. In both studies, the women expressed difficulties in making contact with the health care service, while the women who did not speak Swedish (Study IV) also had difficulties due to different communication problems. In conclusion, it is important that health care resources are optimized to identify and meet the needs of those who experience major problems with UI, and that there is awareness of the communication difficulties that can be present in meeting with people who speak other languages. However it is also important not to medicalize those who experience minor problems and who have the desire to manage on their own.
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7.
  • Gareis, Daniel, et al. (författare)
  • Mouse MRI using phased-array coils
  • 2007
  • Ingår i: NMR in Biomedicine. ; 20:3, s. 326-334
  • Tidskriftsartikel (refereegranskat)abstract
    • The advantages of array coil imaging in human whole-body MR systems are well known and have gained relevance in many applications and MR techniques. In the field of small-animal studies, this concept has become increasingly important. In this work, three different phased-array coils for performing MRI on mice are presented. For imaging at 300 MHz, a four-channel receive-only phased-array coil is introduced. One two-channel and a four-channel transmit/receive setup operating at 750 MHz show the feasibility of array coil imaging at 17.6 T. All of these coils show excellent performance and deliver high-quality MR images of mice.
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8.
  • Türkmen, Sahruh, et al. (författare)
  • Tolerance development to Morris water maze test impairments induced by acute allopregnanolone
  • 2006
  • Ingår i: Neuroscience. - : Elsevier Inc.. - 0306-4522 .- 1873-7544. ; 139:2, s. 651-659
  • Tidskriftsartikel (refereegranskat)abstract
    • The progesterone metabolite allopregnanolone, like benzodiazepines, reduces learning and impairs memory in rats. Both substances act as GABA agonists at the GABA-A receptor and impair the performance in the Morris water maze test. Women are during the menstrual cycle, pregnancy, and during hormone replacement therapy exposed to allopregnanolone or allopregnanolone-like substances for extended periods. Long-term benzodiazepine treatment can cause tolerance against benzodiazepine-induced learning impairments. In this study we evaluated whether a corresponding allopregnanolone tolerance develops in rats. Adult male Wistar rats were pretreated for 3 days with i.v. allopregnanolone injections (2 mg/kg) one or two times a day, or for 7 days with allopregnanolone injections 20 mg/kg intraperitoneally, twice a day. Thereafter the rats were tested in the Morris water maze for 5 days and compared with relevant controls. Rats pretreated with allopregnanolone twice a day had decreased escape latency, path length and thigmotaxis compared with the acute allopregnanolone group that was pretreated with vehicle. Pretreatment for 7 days resulted in learning of the platform position. However, the memory of the platform position was in these tolerant rats not as strong as in controls only given vehicle. Allopregnanolone treatment was therefore seen to induce a partial tolerance against acute allopregnanolone effects in the Morris water maze.
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9.
  • Akanda, Nesar, 1972- (författare)
  • Voltage-dependent anion channels (VDAC) in the plasma membrane induce apoptosis
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Apoptosis, or programmed cell death, is essential for proper development and functioning of the body systems. During development, apoptosis plays a central role to sculpt the embryo, and in adults, to maintain tissue homeostasis by eliminating redundant, damaged or effete cells. Therefore, a tight regulation of this process is essential. Cell shrinkage associated efflux of K+ and Cl– through plasma membrane ion channels is an early event of apoptosis. However, little is known about these fluxes. The aim of this thesis was to investigate ion channels in the plasma membrane of neurons undergoing apoptosis. We studied differentiated (the mouse hippocampal cell line HT22, the human neuroblastoma cell line SK-N-MC, and rat primary hippocampal neurons) and undifferentiated (rat primary cortical neural stem cells cNSCs) cells with the patch-clamp technique. All cell types displayed a low electrical activity under control conditions. However, during apoptosis in differentiated neurons, we found an activation of a voltage-dependent anion channel. The conductance of the channel is 400 pS, the voltage dependence of the opening is bell shaped with respect to membrane voltage with a maximum open probability at 0 mV, and the Cl− to cation selectivity is >5:1. These biophysical properties remind about the voltage-dependent anion channel normally found in the outer mitochondrial membrane (VDACmt). Hence, we call our apoptosis-inducing plasma membrane channel VDACpl. The molecular identity of the channel was corroborated with the specific labelling of different anti-VDAC antibodies. Block of this channel either with antibodies or with sucrose prevented apoptosis, suggesting a critical role for VDACpl in the apoptotic process. VDACpl is a NADH (-ferricyanide) reductase in control cells. We found that the enzymatic activity is altered while the VDACpl channel is activated during apoptosis. Surprisingly, in cNSCs we did not find any activation of VDACpl, no VDACpl-specific labelling, no enzymatic activity, and no prevention of apoptosis with VDACpl-blocking strategies. Instead, we found an activation of a voltage-independent 37 pS ion channel, and that the Cl– channel blocker DIDS prevented apoptosis in cNSCs. Our finding that activation of VDACpl is critical for apoptosis in differentiated neurons hopefully can lead to new strategies in the treatment of several diseases related to apoptosis.
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10.
  • Anderzén-Carlsson, Agneta, 1966- (författare)
  • Children with cancer : focusing on their fear and on how their fear is handled
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Various fears in children with cancer have previously been identified as a result of studying e.g. symptom experiences, distress and uncertainty within this population. Studies of the meaning the children give to their fear, as well as the handling of their fear seem to be sparse, however. Also, fear has not been an exclusive focus in previous studies. Professionals in clinical practice have pointed to the need for such research, which has prompted the present research work. The overall aim of this thesis was therefore twofold; firstly, the aim was to elucidate fear in children and adolescents with cancer in order to gain an understanding from the perspective of adolescents and parents. Secondly, it was to elucidate parents’ and professionals’ handling of the fear. This in order to gain a deeper understanding of what performances and manners the children and adolescents can face when being fearful. A qualitative descriptive design was adopted in the five included studies. The methods used in the data analysis were phenomenological hermeneutical method (studies I–III) and qualitative content analysis (studies IV–V). In study I six adolescent girls, aged 14–16 years, with experiences of various cancer diagnoses, but now declared fit, were interviewed. The results reveal that they experience their fear as embodied, which in the comprehensive understanding of the results was interpreted as a threat to their personal self, their whole existence. Their fear was seen as a holistic intertwined experience, including fear related to the physical body and to the social self. Also, existential fear was described. Their described experience was interpreted as suffering. Studies II and III share the same data. Fifteen parents of children at various ages with various cancer diagnoses were interviewed in focus groups about their experience of their child’s fear. In study II the result reveals how the parents experienced and understood their child’s fear. The fear was described as a multidimensional phenomenon, which was not always easy to identify. It was contrasted to feelings of unease and to absence of fear. In the comprehensive understanding the fear was interpreted as a suffering, as that was regarded to be what was the common meaning in the narratives. The suffering was interpreted as an ethical demand to the parents to take action. In study III the parents described their actions, i.e. they described how they dealt with the fear. Their actions were described as acting in the best interests of the child, which included striving to make the child feel secure and experience wellbeing, up to a certain point. However, after this point the parents used their parental authority to maintain the child’s physical health rather than trying to prevent or relieve the child’s fear. In the comprehensive understanding the parents’ handling of their child’s fear was interpreted as revealing mercy and as being synonymous with meeting the ethical demand put on them. In study IV ten experienced nurses and physicians were individually interviewed about how they handled fear in children with cancer. The result reveals that the existential issues were dealt with within the relationship with the child, on a sliding scale between closeness and distance, and that the fear related to medical procedures occurred on a continuum between support and lack of support. The various actions involved, and the manner in which these actions were performed, was described. In the observational study (study V) eleven parents and their children as well as eleven health professionals participated. They were observed at children’s routine visits at the outpatient clinic. The aim was to study the interactions related to fear. The result reveals that when children were fearful they expressed this both verbally and non-verbally. The parents’ and professionals’ actions and interactions in these situations were found to be characterized by recognition of the fear or lack of attention to the fear. The findings can contribute to a broadened knowledge on fear in children and adolescents with cancer. Awareness and understanding of the meaning adolescents give to their fear, and furthermore, of the parents’ experience and understanding of their child’s fear can provide tools for interacting with these groups. The findings on how fear is dealt with by the ones children have claimed as important sources for support, can give insights into what the child may face when being fearful. These insights can form the basis for individual, as well as collegial, reflections on what is done when children face fear, how fear is handled on an everyday basis and why it is handled in this way. Such reflections could lead to an ethical awareness of handling fear in children with cancer.
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  • Arvidsson, Daniel, 1974, et al. (författare)
  • Energy cost of physical activities in children : Validation of SenseWear Armband
  • 2007
  • Ingår i: Medicine & Science in Sports & Exercise. - : American College of Sports Medicine. - 0195-9131 .- 1530-0315. ; 39:11, s. 2076-2084
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To examine the validity of SenseWear Pro2 Armband in assessing energy cost of physical activities in children, and to contribute with values of energy costs in an overview of physical activities in children. METHODS: Energy cost was assessed by SenseWear Pro2 Armband in 20 healthy children, 11-13 yr, while lying down resting, sitting playing games on mobile phone, stepping up and down on a step board, bicycling on a stationary bike, jumping on a trampoline, playing basketball, and walking/running on a treadmill at the speeds 2, 3, 4, 5, 6, 7, 8, and 10 km x h(-1). During these activities, energy cost was also assessed from VO2 and VCO2 measured by Oxycon Mobile portable metabolic system, which was used as criterion method. RESULTS: The difference in energy cost between SenseWear Pro2 Armband and Oxycon Mobile was -0.7 (0.5) (P < 0.001) for resting, -2.0 (0.9) (P < 0.001) for playing games on mobile phone, -6.6 (2.3) (P < 0.001) for stepping on the step board, -12.0 (3.7) (P < 0.001) for bicycling, -2.7 (11.9) (P = 0.34) for jumping on the trampoline, and -14.8 (6.4) kJ x min(-1) (P < 0.001) for playing basketball. The difference in energy cost between SenseWear Pro2 Armband and Oxycon Mobile for increasing treadmill speed was 1.3 (3.1) (P = 0.048), 0.1 (2.9) (P = 0.82), -1.2 (2.6) (P = 0.049), -1.6 (3.2) (P = 0.044), -3.1 (3.7) (P = 0.0013), -4.9 (3.7) (P < 0.001), -5.3 (3.7) (P < 0.001), and -11.1 (3.5) kJ x min(-1) (P < 0.001). CONCLUSIONS: SenseWear Pro2 Armband underestimated energy cost of most activities in this study, an underestimation that increased with increased physical activity intensity. A table of energy costs (MET values) of physical activities in children measured by indirect calorimetry is presented as an initiation of the creation of a compendium of physical activities in children
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13.
  • Bailey, Leslie, 1975- (författare)
  • Infection biology of Chlamydia pneumoniae
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • There are two main human pathogens in the family of Chlamydiaceae. Different serovars of Chlamydia trachomatis cause sexually-transmitted disease and eye infections whereas C. pneumoniae (TWAR) is a common cause of community-acquired respiratory infection. Chlamydia species are obligate, intracellular bacteria sharing a unique developmental cycle that occurs within a protected vacuole termed an inclusion. These microorganisms can be distinguished by two different forms: the infectious, metabolically inert elementary body (EB) and the reproducing non-infectious form, termed the reticulate body (RB). The cycle is terminated when re-differentiation of RBs back to infectious EBs occurs. Chlamydia possesses a type III secretion system (T3SS) essential for delivery of effector proteins into the host for host-cell interactions. This virulence system has been systematically characterized in several mammalian pathogens. Due to lack of a tractable genetic system for Chlamydia species, we have employed chemical genetics as a strategy to investigate molecular aspects of the T3SS. We have identified that the T3S-inhibitors INP0010 and INP0400 block the developmental cycle and interfere with secretion of T3S effector proteins in C. pneumoniae and C. trachomatis, without any cytotoxic effect. We have further shown that INP0010 decreases initiation of transcription in C. pneumoniae during the early mid-developmental cycle as demonstrated by a novel calculation, useful for measurement of transcription initiation in any intracellular pathogen. The mechanism regulating the signal(s) for primary as well as terminal differentiation of RBs has not been defined in Chlamydia. We show using T3S-inhibitors that INP0010 targets the T3SS and thereby arrests RB proliferation as well as RB to EB re-differentiation of C. pneumoniae as where INP0400 targets the T3SS and provokes a bacterial dissociation from the inclusion membrane presumed to mimic the natural occurrence of terminal differentiation. The effect of INP0010 on iron-responsive genes indicates a role for T3S in iron acquisition. Accordingly, our results suggest the possibility that C. pneumoniae acquires iron via the intracellular trafficking pathway of endocytosed transferrin. Moreover, we have for the first time presented data showing generalized bone loss from C. pneumoniae infection in mice. The infection was associated with increased levels of the bone resorptive cytokines IL-6 and IL-1beta. In addition, an increased sub-population of T-cells expressed RANKL during infection. Additionally, C. pneumoniae established an infection in a human osteoblast cell line in vitro with a similar cytokine profile as seen in vivo, supporting a causal linkage. Collectively, these data may indicate a previously unknown pathological role of C. pneumoniae in generalized bone loss.
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14.
  • Bergström, Annika (författare)
  • Dystocia in the bitch : epidemiology, aetiology and treatment
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Dystocia means difficult birth or inability to expel foetuses through the birth canal. The aetiology of dystocia may be maternal or foetal. Primary uterine inertia is the most common reason for dystocia in the bitch approaching 75% of the cases. The objective of this thesis was to investigate the incidence of dystocia and to find causes of primary uterine inertia. Also the treatment regimes for bitches with primary uterine inertia were evaluated. An epidemiologic investigation was performed. A large animal insurance data-base was used which covered healthy as well as diseased animals over time. Incidence of dystocia and the frequency of caesarean section in affected bitches were calculated. The overall incidence of dystocia was 5.7 cases per 1 000 dog years at risk. The frequency of caesarean section in bitches with dystocia was 64%. The other three studies included healthy bitches and bitches with abnormal parturition and the hormonal concentrations were analysed. An increase in prostaglandinF2α-metabolite concentration was observed from the last week of pregnancy. At labour stage II the plasma concentrations of prostaglandinF2α-metabolite, oxytocin, vasopressin and cortisol all increased in normal labour. Bitches with primary uterine inertia had plasma concentration of prostaglandinF2α-metabolite which was significantly lower compared to the normal bitches. The serum electrolytes was analysed in bitches with normal and abnormal parturition. No evidence was found indicating that abnormal serum concentration of electrolytes was a cause of primary uterine inertia in the bitch. Evaluation of two different treatment regimes revealed no significant difference in labour outcome if the bitch was treated with calcium solution in combination with oxytocin or with oxytocin only. In summary, this thesis provides information about the incidence of dystocia which was earlier unknown. The results suggest that abnormal release or production of prostaglandinF2α may be a cause of primary uterine inertia in bitches.
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16.
  • Börjesson, Andreas, 1976- (författare)
  • Investigations of Strategies to Counteract Proinflammatory Cytokines in Experimental Type 1 Diabetes
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Type 1 diabetes (T1D) is a chronic autoimmune disease targeted against the pancreatic β-cells. Proinflammatory cytokines are considered to play a major role in the destruction of the insulin-producing β-cells. This thesis studied strategies to counteract proinflammatory cytokines in experimental T1D. Both animal models for T1D as well as β-cell preparations exposed in vitro to putative noxious conditions were examined.In the first study we observed that cytokine treatment of mouse pancreatic islets lacking inducible nitric oxide synthase (iNOS) induced a prolongation of the early stimulatory phase of glucose stimulated insulin secretion. Various experiments led to the conclusion that this prolonged stimulatory effect may involve the DAG/PLD/PKC pathway.Next, we transplanted mouse islets deficient in iNOS to spontaneously diabetic NOD mice. We observed a normalization of hyperglycemia but not a delayed allograft rejection compared to transplanted wild type islets. Thus, absence of iNOS in the graft was not sufficient to prolong allograft survival.In paper III we found that sustained glucose stimulation of rat pancreatic islets was coupled to a decreased conversion of proinsulin to insulin. Islet treatment with IL-1β was also coupled to a decreased proinsulin conversion. Islet proconvertase activity may be a target in islet damage.In paper IV prolactin (PRL) was administered to mice in the multiple low dose streptozotocin model and we observed that PRL enhanced a Th2 response. This may contribute to the protective action by PRL in this model of autoimmune T1D.Finally, by examining β-cells overexpressing Suppressor of cytokine signalling 3 (SOCS-3) it was found that this could inhibit IL-1β induced signalling through the NF-κB and MAPK pathways. SOCS-3 overexpression also inhibited apoptosis induced by cytokines in primary β-cells. Lastly, we demonstrated that SOCS-3 transgenic islets were protected in an allogeneic transplantation model.
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17.
  • Böttiger, Anna, 1977- (författare)
  • Genetic variation in the folate receptor-alpha and methylenetetrahydrofolate reductase genes as determinants of plasma homocysteine concentrations
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Elevated total plasma homocysteine (tHcy) is a risk factor for cardiovascular disease and neurocognitive disease such as dementia. The B vitamins folate and B12 are the main de terminants of tHcy. tHcy concentration can also be affected by mutations in genes coding for receptors, enzymes and transporters important in the metabolism of Hcy. This thesis focuses on mutations in the genes for folate receptor-alpha and methylenetetrahydrofolate reductase (MTHFR) and the effect they have on tHcy concentrations. Six novel mutations in the gene for folate receptor-alpha were described in Paper I. Taken together they exist in a population with a prevalence of approximately 1% and thus are not unusual. There may be an association of –69dupA and –18C>T to tHcy but for the 25-bp deletion, –856C>T, –921T>C and –1043G>A there is probably no association to tHcy. Mutation screening was continued and four additional mutations, 1314G>A, 1816delC, 1841G>A and 1928C>T, were described in Paper II. The prevalences for the heterozygotes were between 0.5% and 13% in an elderly population. There was no significant difference in prevalence between the elderly subjects and patients with dementia. The 1816(–)-allele and the 1841A-allele were in complete linkage and the haplotype 1816(–)-1841A may possibly have a tHcy raising effect. The 1314G>A and 1928C>T mutations had no association to tHcy. The genotype prevalences and haplotype frequencies of the MTHFR 677C>T, 1298A>C and 1793G>A polymorphisms were determined in a population sample of Swedish children and adolescents (Paper III). The MTHFR 677T-allele was associated with increased tHcy concentrations in both children and adolescents. A small elevating effect of the 1298C-allele and a small lowering effect of the 1793A-allele could be shown. In an epidemiological sample of adults from the Canary Islands, Spain, data for serum folate and vitamin B12 were used for a broader study of the nutrigenetic impact on tHcy (Paper IV). The 677T-allele had a significant tHcy increasing effect in men but not in women. The 1298C-allele had a minor elevating effect on tHcy in men with the 677CT genotype. It was not possible to document any effect of the 1793A-allele on tHcy due to its low prevalence. A slightly superior explanatory power for the genetic impact was obtained using the MTHFR haplotypes in the analysis compared to the MTHFR 677C>T genotype-based approach in both the Swedish children and adolescents and in the Spanish adults. Therefore MTHFR haplotypes should be considered when analysing the impact of the MTHFR 677C>T, 1298A>C and 1793G>A polymorphisms on tHcy. Notwithstanding the large geographical distance between our study populations the haplotype composition is quite similar. The MTHFR 677T-allele is slightly more prevalent in Spain compared to Sweden but it has only an effect on tHcy in the Spanish men. Age, gender and factors linked to the ethnicity of the studied subjects, seem to be able to override the nutrigenetic impact of tHcy-raising genotypes or haplotypes in particular settings, such as in the Spanish women in our study. Gene-nutrient interactions on plasma tHcy levels thus may or may not exist in a certain population. The transferability of nutrigenetic findings may therefore be limited, and must be re-evaluated for each particular setting of age-gender-ethnicity.
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18.
  • Capurro, Aldo (författare)
  • Diagnostic and epidemiological studies of staphylococci in bovine mastitis
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Diagnostic and epidemiological studies of staphylococci in bovine mastitis.Mastitis is the most common disease in dairy cows and is often caused by staphylococcal infections. The genus Staphylococcus is divided in coagulase-negative (CNS) and coagulase-positive (CPS) staphylococci. The CPS S. aureus is the most prevalent udder pathogen in Swedish dairy cows. For successful mastitis control accurate diagnostics and good understanding of the bacterial epidemiology is essential. This thesis describes methods for species differentiation within CNS and CPS, examines genotypic diversity of S. aureus isolates within Sweden, and identifies potential sources of S. aureus in herds with mastitis problems. First, three phenotypic tests (P-agar with acriflavin, β-galactosidase, and haemolytic reaction in chocolate agar) of eight biochemical tests evaluated were found useful for differentiation between the CPS species, S. aureus, S. hyicus and S. intermedius. The proportions of each species among bovine milk isolates were 97%, 1%, and 2%, respectively. Then, species identification of CNS using the Staph-Zym™ test was compared with sequencing of part of the tuf gene. Staph-Zym™ correctly identified 61%, but gave an incorrect species name in 28% of the milk isolates. Supplementary tests were frequently needed when using Staph-Zym™. In the next study, S. aureus isolates from a national survey on acute clinical mastitis were genotyped using pulsed-field gel electrophoresis (PFGE), and 25 pulsotypes (PTs) were identified. Three of the PTss accounted for over 50% of the isolates and were found all over the country. The distribution of PTs was different in the southern region than in the northern and middle regions of the country. Finally, S. aureus PTs in quarter milk samples, body samples (BS), and environment samples (ES) from various animal groups were studied in five herds with S. aureus mastitis problems. Herd differences were found, but all herds had one predominant unique milk PTs. In three farms this PTs was often found in BS and ES of lactating cows, and occasionally in samples from the other groups.
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19.
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20.
  • Cristea, Alexander, 1966- (författare)
  • Effects of Ageing and Physical Activity on Regulation of Muscle Contraction
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aims of this study were to investigate the mechanisms underlying (1) the ageing-related motor handicap at the whole muscle, cellular, contractile protein and myonuclear levels; and (2) ageing-related differences in muscle adaptability.In vivo muscles function was studied in the knee extensors. Decreases were observed in isokinetic and isometric torque outputs in old age in the sedentary men and women and elite master sprinters. A 20-week long specific sprint and resistance training successfully improved the maximal isometric force and rate of force development in a subgroup of master sprinters.In vitro measurements were performed in muscle biopsies from the vastus lateralis muscle. Immunocytochemical and contractile measurements in single membrane permeabilized muscle fibres demonstrated ageing- and gender-related changes at the myofibrillar level. In sedentary subjects, data showed a preferential decrease in the size of muscle fibres expressing type IIa MyHC in men, lower force generating capacity in muscle fibres expressing the type I MyHC isoform in both men and women and lower maximum velocity of unloaded shortening (V0) in fibres expressing types I and IIa MyHC isoforms in both men and women. The master sprinters also experienced the typical ageing-related reduction in the size of fast-twitch fibres, a shift toward a slower MyHC isoform profile and a lower V0 of type I MyHC fibres, which played a role in the decline in explosive force production capacity. The fast-twitch fibre area increased after the resistance training period. A model combining single muscle fibre confocal microscopy with a novel algorithm for 3D imaging of myonuclei in single muscle fibre segments was introduced to study the spatial organisation of myonuclei and the size of individual myonuclear domains (MNDs). Significant changes in the MND size variability and myonuclear organization were observed in old age, irrespective gender and fibre type. Those changes may influence the local quantity of specific proteins per muscle fibre volume by decreased and/or local cooperativity of myonuclei in a gender and muscle fibre specific manner.In conclusion, the ageing-related impairments in in vivo muscle function were related to significant changes in morphology, contractile protein expression and regulation at the muscle fibre level. It is suggested that the altered myonuclear organisation observed in old age impacts on muscle fibre protein synthesis and degradation with consequences for the ageing-related changes in skeletal muscle structure and function. However, the improved muscle function in response to a 20-week intense physical training regime in highly motivated physically active old subjects demonstrates that all ageing-related in muscle function are not immutable.
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21.
  • Egenvall, Agneta, et al. (författare)
  • Mortality of Life-Insured Swedish Cats during 1999-2006: Age, Breed, Sex, and Diagnosis
  • 2009
  • Ingår i: Journal of Veterinary Internal Medicine. - : Wiley. - 0891-6640 .- 1939-1676. ; 23, s. 1175-1183
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundA cat life insurance database can potentially be used to study feline mortality.HypothesisThe aim was to describe patterns of mortality in life-insured Swedish cats.CatsAll cats (< 13 years of age) with life insurance during the period 1999-2006 were included.MethodsAge-standardized mortality rates (MR) were calculated with respect to sex (males and females), age, breed, and diagnosis. Survival to various ages is presented by time period and breed.ResultsThe total number of cats insured was 49,450 and the number of cat-years at risk (CYAR) was 142,049. During the period, 6,491 cats died and of these 4,591 cats (71%) had a diagnosis, ie, were claimed for life insurance. The average annual MR was 462 deaths per 10,000 CYAR (95% confidence interval, 431-493). Sex-specific rates did not differ significantly. The overall mortality of the Persian and the Siamese groups was higher than that of several other breeds. Overall and breed-specific (for most breeds) survival increased with time when analyzed by 2-year periods. The 6 most common diagnostic categories (ignoring cats recorded as dead with no diagnosis) were urinary, traumatic, neoplastic, infectious, cardiovascular, and gastrointestinal. The MR within diagnostic categories varied by age and breed.Conclusions and Clinical ImportanceIn this mainly purebred, insured cat population, the overall mortality varied with age and breed but not with sex. The increase in survival over time is likely a reflection of willingness to keep pet cats longer and increased access to and sophistication of veterinary care.
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22.
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23.
  • Eliasson, Henrik, 1958- (författare)
  • Tularemia : epidemiological, clinical and diagnostic aspects
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Tularemia is a zoonosis caused by the small, fastidious, gram-negative rod Francisella tularensis that appears over almost the entire Northern Hemisphere. In Sweden, tularemia has appeared mainly in restricted areas in northern parts of central Sweden. The disease can be transmitted through several routes: direct contact with infected animals, by vectors, through contaminated food or water or through inhalation of aerosolized bacteria. Distinct clinical forms of the disease are seen, depending on the route of transmission. During the last years, tularemia has emerged in new areas in central Sweden, south of the endemic area. The emergence of tularemia in the County of Örebro prompted the investigations presented in this thesis. We performed a case-control study, using a mailed questionnaire, to identify risk factors for acquiring tularemia in Sweden (Paper I). After multivariate analysis, mosquito bites and cat ownership could be associated with tularemia in all studied areas while farming appeared as a risk factor only in endemic areas. In Paper II, we evaluated a PCR analysis, targeting the tul4 gene, used on samples from primary lesions in patients with ulceroglandular tularemia. The method performed well, with a sensitivity of 78% and a specifi city of 96%. The clinical characteristics of tularemia in an emergent area in Sweden were studied Paper III), using case fi les and a questionnaire. Of 278 cases of tularemia reported during the years 2000 to 2004, 234 had been in contact with a doctor from the Department of Infectious Diseases at Örebro University Hospital, and were thus included. The ulceroglandular form of the disease was seen in 89% of the cases, with the primary lesion, in most cases, on the lower leg. An overwhelming majority of cases occurred during late summer and early autumn, further supporting transmission by mosquitoes. Erythemas overlying the affected lymph node areas were seen in 19% of patients with forms of tularemia affecting peripheral lymph nodes. Late skin manifestations, of various appearances, were seen in 30% of the cases, predominantly in women. A raised awareness of tularemia among physicians in the county during the course of the outbreak was found, as documented by the development of shorter doctor’s delay and less prescription of antibiotics inappropriate in tularemia. Finally, we developed a simplifi ed whole-blood lymphocyte stimulation test, as a diagnostic tool in tularemia (Paper IV). The level of IFN-γ, as a proxy for lymphocyte proliferation, was measured after 24-h stimulation. Additionally, a tularemia ELISA with ultra-purifi ed LPS as the antigen was evaluated, showing a high sensitivity. The lymphocyte stimulation test, when performed on consecutive samples from subjects with ongoing tularemia was able to detect the disease earlier in the course of the disease than both the new ELISA and the tube agglutination test. Furthermore, all tularemia cases became positive in the lymphocyte stimulation test within 12 days of disease. In conclusion, this thesis describes risk factors for acquiring tularemia as well as the clinical characteristics of the disease in Sweden. Additionally, a Francisella PCR analysis and a tularemia ELISA based on highly purifi ed LPS is evaluated, and a simplified lymphocyte stimulation test, for early confirmation of the disease, is developed.
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24.
  • Eriksson, Marie, 1970- (författare)
  • Aspects on stroke outcome : survival, functional status, depression and sex differences in Riks-Stroke, the National Quality Register for Stroke Care
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Stroke is a major cause of death and disability worldwide. In Sweden, about 30 000 strokes occur each year. The aim of this thesis was to analyse survival, functional outcome and self-reported depression after stroke, and to explore possible differences between men and women in stroke care and outcome. These studies were based on Riks-Stroke, the Swedish national quality register for stroke care. Information on background variables and treatment were collected during the hospital stay. The patient’s situation and outcome after stroke were followed-up after 3 months. Long term survival was retrieved from the Swedish Population Register (Folkbokföringen). Possible sex-differences in stroke care and outcome 3 months after stroke were explored in 24 633 strokes, registered during 2006. In conscious patients, the proportions treated at stroke units were similar for men and women. Men and women had equal chance to receive thrombolytic therapy or secondary prevention with oral anticoagulants. Compared to men, women were less likely to develop pneumonia, but more likely to experience deep venous thromboses and fractures during hospital stay. Women had worse 3-month survival and functional outcome, differences that were explained by their higher age and impaired level of consciousness on admission. Women felt more depressed and perceived their health as worse than men did. Women were also less satisfied with the care they had received in the hospital. The agreement between self-reported functional outcome 3 months after stroke and the commonly used modified Rankin Scale (mRS) was explored in 555 stroke survivors from 4 hospitals during May-September 2005. Riks-Stroke’s self-reported questions classified 76% of the patients into correct mRS grade. The association between functional outcome 3 months after stroke and 3-year survival was assessed in 15 959 men and women who had had a stroke during 2001-2002. Patients with estimated mRS grades 3, 4 and 5 had hazard ratios for death of 1.7, 2.5 and 3.8, respectively, as compared with patients with lower grades, 0-2. Depressed mood, male sex, high age, diabetes, smoking, antihypertensive therapy at onset and atrial fibrillation were also identified as predictors of poor survival. Self-reported depression 3 months after stroke and use of antidepressants were analysed in 15 747 stroke survivors from 2002. Fourteen percent felt depressed 3 months after stroke. Female sex, age <65, previous stroke, living alone or in institution, or being dependent in activities of daily living (ADL) were factors associated with self-reported depression. At the follow-up, 22% of the men and 28% of the women were using antidepressant medication, which were approximately twice as many as in the general population. Still, 8% of all patients in Riks-Stroke reported depressive mood but no treatment with antidepressants. In conclusion, men and women with stroke in Sweden experience similar treatment and outcome in most aspects. Patient-reported functional outcome can be reliably transformed to a standard disability scale. Impaired functional outcome three months after stroke is an independent predictor of poor long-term survival. Depressive mood is common after stroke and is associated with poor survival and impaired functional outcome.
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25.
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26.
  • Fuchs, Dieter, 1979- (författare)
  • Novel Treatment Modalities for High-Risk Neuroblastoma : Studies in Animal Models
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Neuroblastoma, the most common extracranial solid tumor of childhood, is a heterogeneous tumor. In some patients, the tumor can go into spontaneous regression and disappear whereas other patients have rapidly growing tumors with a poor prognosis. The overall long-term survival rate in patients with high-risk neuroblastoma is less than 30%, indicating the need for new treatment strategies. Angiogenesis inhibition hampers the formation of new blood vessels, thereby limiting the tumors’ metabolic exchange. Neuroblastoma is rapidly growing and high tumor angiogenesis has been associated with poor outcome. Therefore, the aim of this thesis was to investigate the effect of novel treatment modalities for angiogenesis inhibition on high-risk neuroblastoma xenografts. For that purpose, we used subcutaneous mouse models and characterized orthotopic mouse models for high-risk neuroblastoma. We found that xenotransplantation of neuroblastoma cells into the adrenal gland of SCID and SCID beige mice resulted in orthotopic tumors resembling clinical neuroblastoma in respect to tumor site, growth and spread. Using contrast-enhanced ultrasound, we observed that the receptor tyrosine kinase inhibitor SU11248 reduced orthotopic neuroblastoma growth and spread by reducing tumor angiogenesis.In subcutaneous xenografts for high-risk neuroblastoma, valuable for studies requiring continuous assessment of tumor volume, we demonstrated that immune-neutralizing VEGF with the anti-VEGF antibody bevacizumab significantly reduced neuroblastoma growth. Finally, we found that formulations of the chemotherapeutic drug GMX1778 inhibited angiogenesis and induced tumor regression in a dose dependent manner without host toxicity. We showed that relapsing tumors remained responsive to GMX-therapy without accelerated growth or induced drug resistance.In conclusion, SU11248, bevacizumab, and formulations of the active compound GMX1778 may become useful for treating high-risk neuroblastoma.
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27.
  • Gisslén, Karl, 1967- (författare)
  • The patellar tendon in junior elite volleyball players and an Olympic elite weightlifter
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The principal aim of the present thesis was to prospectively follow (clinical status and ultrasound + Doppler findings) the patellar tendons in the young elite volleyball players at the Swedish National Centre for high school volleyball in Falköping. In an Olympic weightlifter with chronic painful jumper´s knee, the effects of treatment with sclerosing injections followed by early instituted very heavy weightlifting training, was also evaluated. First, in a prevalence study, we demonstrated that the clinical diagnosis patellar tendinopathy-jumper’s knee, together with structural tendon changes and vascularisation in the painful area of the tendon, was demonstrated in 12/114 tendons in Swedish junior elite volleyball players, but not in any tendons of individually matched (age, height and weight) not regularly sports active controls. Structural tendon changes alone was demonstrated among the volleyball players but also among the controls. In a 7 months prospective study of a total of 120 tendons, we demonstrated that the clinical diagnosis patellar tendinopathy-jumper’s knee was associated with neovessels/vascularity in the area with structural tendon changes in 17/19 tendons. Seventy tendons that at start were clinically normal, and had normal ultrasound + Doppler findings, remained clinically normal after 7 months with intensive training and playing volleyball. In a 3-year prospective study it was demonstrated that normal clinical tests and normal ultrasound + Doppler findings at school start, indicated a low risk (8%) for these players to sustain patellar tendinopathy-jumper’s knee during the 3 school years with intensive training and playing. In a case study, involving an Olympic elite weightlifter with chronic painful patellar tendinopathy-jumper’s knee, successful treatment with ultrasound and Doppler-guided injection of the sclerosing agent polidocanol, allowed for pain-free very heavy weight training two weeks after treatment. Further heavy weightlifting training on a daily basis, preparing for European Championships, was done without causing tendon rupture and/or pain. Key words: Jumper’s knee, Patellar tendinopathy, Chronic pain, Ultrasonography, Doppler, Neovascularisation, Volleyball, Weightlifting
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28.
  • Guez, Michel, 1962- (författare)
  • Chronic neck pain : An epidemiological, psychological and SPECT study with emphasis on whiplash-associated disorders
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Chronic neck pain, a common cause of disability, seems to be the result of several interacting mechanisms. In addition to degenerative and inflammatory changes and trauma, psychological and psychosocial factors are also involved. One common type of trauma associated with chronic neck pain is whiplash injury; this sometimes results in whiplash-associated disorder (WAD), a controversial condition with largely unknown pathogenetic mechanisms. We studied the prevalence of chronic neck pain of traumatic and non-traumatic origin and compared the prevalence of, sociodemographic data, self-perceived health, workload and chronic lowback pain in these groups. In a ready-made questionnaire (MONICA study), we added questions about cervical spine and low-back complaints. 6,000 (72%) completed a self-administered questionnaire. 43% reported neck pain: 48% of women and 38% of men. Women of working age had more neck pain than retired women, a phenomenon not seen in men. 19% of the studied population suffered from chronic neck pain and it was more frequent in women. A history of neck trauma was common in those with chronic neck pain. Those with a history of neck trauma perceived their health worse and were more often on sick-leave. About 50% of those with traumatic and non-traumatic chronic neck pain also had chronic low-back pain. We assessed the subjective and objective neuropsychological functioning in 42 patients with chronic neck pain, 21 with a whiplash trauma, and 21 without previous neck trauma. Despite cognitive complaints, the WAD patients had normal neuropsychological functioning, but the WAD group especially had deviant MMPI results—indicating impaired coping ability and somatization.WAD patients had no alterations in cerebral blood-flow pattern, as measured by rCBF-SPECT and SPM analysis, compared to healthy controls. This contrasts with the non-traumatic group with chronic neck pain, which showed marked blood-flow changes. The blood-flow changes in the non-traumatic group were similar to those described earlier in pain patients but— remarkably enough—were different from those in the WAD group. Chronic neck pain of whiplash and non-traumatic origin appears to be unique in some respects. A better understanding of the underlying pathological mechanisms is a prerequisite for prevention of the development of such chronic pain syndromes and for improvement of the treatment of patients with severe symptoms.
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29.
  • Hahn-Strömberg, Victoria, 1971- (författare)
  • Cell adhesion proteins in different invasive patterns of colon carcinomas : a morphometric and molecular genetic study
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Colorectal carcinoma is the second most common type of cancer in both men and women in Sweden. Cancer of the colon and rectum are often considered together and their ten year survival rate is approximately 50 – 60 % depending on sex and location. Different histopathological characteristics of such cancers, including the complexity of growth, are of importance for prognosis. This thesis has compared different morphometric methods in order to achieve a quantitative and objective measurement of the invasive front of colon carcinoma. Since the growth pattern is dependent on the cell adhesiveness of different proteins we studied the distribution and localization of E-cadherin, Beta-catenin, Claudin 1,2,7 and Occludin as well as screened the genes for mutations. We found a perturbed protein expression of E-cadherin, Beta-catenin, Claudin 1,2,7 and Occludin in tumor sections compared to normal mucosa, but no relation to tumor volume or growth pattern could be seen. The tumor volume was found to be correlated to the growth pattern but not responsible to the perturbed protein expression. In the mutation screening we found a SNP in exon 13 the E-cadherin gene in the tumor, as well as in exon 2 of Claudin 1 and exon 4 of Claudin 7 in both tumor and normal mucosa. No correlation between mutations and growth pattern or tumor volume was found. In conclusion, this thesis shows that the computer image analysis with estimation of fractal dimension and number of free tumor cell clusters is superior to the semi quantitative visual grading of tumor invasive complexity. The aberrant expression of cell adhesion proteins in the tumor compared to normal mucosa as well as polymorphisms in the cell adhesion genes CLDN1 and CLDN7 in both tumor and normal mucosa can suggest that these aberrations are important in the tumorigenesis of colon carcinoma.  
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30.
  • Hjelmblink, Finn, 1939- (författare)
  • Understanding Life After Stroke
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Stroke is an acute, neurological dysfunction of vascular origin with sudden occurrence and it influences physical, cognitive and psychological functions. Initial treatment aims at eliminating or reducing the brain damage. Soon, however, the influence of the stroke on the entire life of stroke survivors has to be considered.This thesis explores the meaning of life after stroke to 19 elderly stroke survivors during the first year post stroke. Survivors were interviewed twice and the interviews were analysed through qualitative methods.Study I was about four survivors who delayed hospital arrival far beyond time limits for trombolytic treatment. The survivors had a strong need for control of body, autonomy and integrity and they demanded to be encountered in consultations as a person by a person. To make them search for emergency evaluation in time might demand an emergency care treating them according to these needs.In Study II the voice of an aphasic survivor was heard. Because of the damaged language his rehabilitation unilaterally focussed on language training and his need for comprehensive support and planning for the future was not observed. Implementation of a qualitative research method for text analysis adapted to practical use in dialogues with aphasic persons might ensure these survivors an adequate rehabilitation.Study III showed how time models in narratives helped stroke survivors to overcome uncertainty and recreate narrative coherence in their lives. Professionals can support survivors through revealing and reinforcing the meaning of these models.Study IV found that the meaning of rehabilitation to stroke survivors was social reintegration. Many probably did not socially reintegrate because their own strategies and subjectively experienced disabilities were unacknowledged in their rehabilitation. Through integrating illness-as-lived perspectives with biomedical perspectives, subjective dysfunctions and rehabilitation strategies of survivors could be acknowledged in stroke rehabilitation.
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31.
  • Holdstock, Camilla, 1975- (författare)
  • Gastric Bypass in Morbid Obesity : Postoperative Changes in Metabolic, Inflammatory and Gut Regulatory Peptides
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis examines the effect of surgical weight loss on gut and adipose tissue peptides involved in appetite regulation and energy homeostasis in morbidly obese humans. Roux-en-Y gastric bypass (RYGBP) is the gold standard operation used for effective long-term weight loss and improved health. The exact mechanisms for this outcome are under investigation.We measured ghrelin, a recently discovered hunger hormone, insulin, adiponectin and leptin along with anthropometry measures in 66 morbidly obese patients prior to and 6 and 12 months after RYGBP. Impressive weight loss occurred postoperatively as did alterations in the peptides. Consistent correlations were found between weight, leptin, ghrelin and insulin. The main findings were low ghrelin concentrations in obesity and an increase after RYGBP.We explored inflammatory proteins C-reactive protein (CRP), serum amyloid A and interleukin-6 before and during massive weight loss 6 and 12 months after RYGBP in morbidly obese subjects. The studied proteins declined after surgery and a correlation between CRP and homeostatic model of assessment for insulin resistance, independent of BMI, strongly linked insulin resistance and inflammation. CRP declined most in insulin-sensitive subjects.We examined the excluded stomach mucosa and vagus nerve by measuring gastrin, pepsinogen I (PGI), pancreatic polypeptide (PP) and ghrelin levels during week 1 and year after RYGBP. Ghrelin levels rose with weight loss but declined 24-hours after surgery, like PP, indicating transient vagal nerve damage. Low levels of gastrin and PGI suggest a resting mucosa.We evaluated gut peptides: peptide YY (PYY), glucaogon like peptide-1 (GLP-1), pro-neurotensin (pro-NT) and PP, in lean (young and middle-aged), obese and postoperative RYGBP subjects pre- and postprandially. RYGBP subjects had exaggerated levels of PYY and GLP-1 postprandially and higher basal proNT levels, implying a ‘satiety peptide tone’ that may contribute to the maintenance of weight loss.In summary, RYGBP results in marked weight loss and alterations in gut and adipose tissue peptides involved in appetite regulation and energy homeostasis. These postoperative peptide changes may contribute to impressive weight loss observed after RYGBP.
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33.
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34.
  • Höglund, Johanna Karolina (författare)
  • Overlapping chromosomal regions for fertility traits and production traits in the Danish Holstein population
  • 2009
  • Ingår i: Journal of Dairy Science. - : American Dairy Science Association. - 0022-0302 .- 1525-3198. ; 92, s. 5712-5719
  • Tidskriftsartikel (refereegranskat)abstract
    • Before implementing selection based on quantitative trait loci (QTL) for fertility, it is important to determine the existence of correlated effects between the fertility QTL and QTL with effects on production traits. When a QTL is detected for a trait that is a composite of subtraits, it is of interest to validate which of the subtraits are affected by the QTL. Phenotypic and marker data were collected from 34 grandsire families from the Danish Holstein population. First, the trait data for "fertility treatments" were separated into their underlying subtraits: uterine infections, antibiotics placed in the placenta, and abortions. In addition, retained placenta was selected for analysis because it is related to uterine infections. A genome scan was performed using 416 microsatellite markers for the fertility treatment subtraits and retained placenta, and an additional genome scan for milk production traits conditional on the QTL regions for the subtraits and retained placenta was conducted. Second, we selected 24 genomic regions harboring QTL for fertility traits from a previous study. A QTL scan for milk production traits conditional on the selected regions was conducted. We found that 16 selected genomic regions containing a QTL for fertility (including the fertility treatment subtraits and retained placenta) also harbored QTL for milk yield or milk composition traits. Furthermore, 12 QTL regions corresponding to 9 different fertility traits (including the fertility treatment subtraits) did not harbor a QTL for milk production or milk composition traits; that is, the region was specific for the fertility trait. The genome scan for the fertility treatment subtraits did not correspond to the QTL found for fertility treatments. No QTL were detected for the subtrait abortion, however genome scans for retained placenta revealed 4 different QTL.
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35.
  • Jansson, Desirée (författare)
  • Genus Brachyspira in birds : phenotypes, phylogeny and pathogenicity
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Spirochaetes of genus Brachyspira colonize the large intestine of some mammals and birds, and cause intestinal disease and production losses in pigs and chickens. The precise significance of Brachyspira spp. colonization in birds, the bacterial species involved, and the epidemiology are incompletely understood. Possible transmission between birds and mammals, and the role of wildlife have previously received little attention. In this thesis intestinal spirochaetes were isolated from commercial laying hens and free-living wild mallards (Anas platyrhynchos), jackdaws (Corvus monedula), rooks (C. frugilegus) and hooded crows (C. corone cornix). The isolates were investigated by phenotypic tests, molecular methods (PCR, RAPD, PFGE, sequencing of 16S rRNA and nox genes) and phylogenetic analysis. Experimental animal models were applied in pigs and mallards to study colonization rates and enteropathogenicity. The results showed that Brachyspira spp. were commonly isolated from the investigated species. Phenotypic and molecular analyses showed considerable diversity, and simultaneous colonization by two or more species or genetic variants of the same species was commonly found. In laying hens, pathogenic species (B. intermedia and B. alvinipulli), presumed non-pathogenic species (B. innocens, murdochii, ‘B. pulli’), and isolates that could not be assigned to any presently known species were isolated. No association with disease or production losses was identified. The etiologic agent of swine dysentery, B. hyodysenteriae, was isolated from mallards, which is the first time from wild birds. A putative novel species, ‘B. suanatina’, was isolated from mallards and Swedish and Danish pig herds. Isolates from both a pig and a mallard were shown to cause diarrhoea in pigs by experimental challenge. In mallards, focal epithelial changes were observed with B. hyodysenteriae and ‘B. suanatina’. Another novel and presumed non-pathogenic species, ‘B. corvi’, from corvid birds, was characterized and provisionally described. The results of the thesis highlight the diagnostic difficulties, the genetic diversity, and suggest that birds may be important reservoirs of Brachyspira spp.
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36.
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37.
  • Jemtå, Lena, 1965- (författare)
  • Children and Adolescents Living with Mobility Impairment
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Aim: This thesis aims to describe perceived overall well-being, coping strategies, experiences of intimacy and sexuality, and global and dimension-specific self-esteem among children and adolescents with mobility impairment. Methods: The study included 141 children and adolescents aged 7–18 years with mobility impairment. Data was gathered by comprehensive semi-structured interviews and the self-report inventories “Children’s Coping Strategies Checklist” (CCSC) and “I Think I am”. Perceived overall well-being was measured by the nine-grade visual “Snoopy scale”. Motor function and pain were measured by the BL motor assessment, and independence or dependence by Katz Index of Independence in Activities of Daily Living. Results: The majority reported a favourable level of perceived overall well-being and positive global and dimension-specific self-esteem. Lower global self-esteem was significantly related to: greater age, being a first-generation immigrant, having an acquired disease or injury and experience of pain, while lower level of perceived overall well-being was significantly related to all of these in addition to not living with both parents. Generally, children and adolescents identified themselves as sexual beings and most expressed future aspirations as living together with partner having children. However, many had limited or no experience of partner-related intimacy and sexual activities, and socio-demographic and disability characteristics had a marginal influence. A history of sexual abuse was reported by 7% in the age cohort 13–18 years. A four-dimensional model of coping strategies including “active coping”, “distraction”, “avoidance” and “support seeking” strategies provided an adequate fit to the CCSC data. Three of the four strategies, all except “avoidance”, were significantly related to several demographic and disability features. Well-being was not significantly related to coping strategies, although the higher the trust in the strategies, the higher the estimation of well-being. Conclusion: The understanding of vulnerability factors as well as identification of coping strategies among children and adolescents with mobility impairment is essential for providing proper care, treatment and support during childhood and adolescence.
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38.
  • Jiang, Wei, 1964- (författare)
  • Regeneration in the adult brain after focal cerebral ischemia : exploration of neurogenesis and angiogenesis
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Ischemic stroke ranks as the third major cause of clinical mortality and the leading cause of handicap in adults. Each year, stroke occurs in about 30,000 Swedes. The severity of an acute ischemic stroke depends mainly on the degree and duration of local cerebral blood flow (lCBF) reduction. Prompt reperfusion improves neurological deficits, spontaneous electrical activity, energy metabolism, cerebral protein synthesis (CPS), and tissue repair, among which cell proliferation (neurogenesis, gliosis) and revascularization (angiogenesis) may have important functional and therapeutic implications.Aims of the thesis: (1) To establish the photothrombotic ring stroke(PRS) model with late spontaneous reperfusion in adult mice; (2) To explore angiogenesis and neurogenesis in adult brain after focal cerebral ischemia.Materials and Methods: The PRS model in C57 BL adult mice and the middle cerebral artery suture occlusion (MCAO) model in adult Wistar rats were used. The 5-bromodeoxyuridine (BrdU) was delivered into animal after stroke induction to label DNA duplication. CBF, CPS and adenosine triphosphate (ATP) were measured by laser-Doppler flowmetry (LDF), [14C]–Iodoantipyrine and [3H]-Leucine double tracer autoradiography, and bioluminescence, respectively. Immunocytochemistry / immunofluoresence were performed to detect different proteins. The cell marker colocalization was analyzed by three-dimension (3-D) confocal. The cell counting was performed with a stereological counting system.Results: The PRS model was established in adult mice by irradiating the exposed skull with a 514.5 nm argon laser ring beam (3 mm diameter, 0.21 mm thick) at an intensity of 0.65 W/cm2 for 60s, with concurrent erythrosin B (4.25 mg/kg) intravenous infusion for 15s. The central cortical region within the ring locus was progressively encroached by an annular ring-shaped perfusion deficit, where lCBF LDF declined promptly to 43% of the baseline value at 30 min post irradiation. The lCBF-IAP amounted to 46-17-58 ml/100g/min, where CPS varied from 57-38-112% at 4h-48h-7days post ischemia. ATP declined at 4h, achieved its maximum level at 48h and was markedly reduced at 7 days postischemia. Morphologically, at 4h some neurons in the region at-risk appeared swollen, at 48h the majority were severely swollen, eosinophilic and pyknotic. Tissue morphology became partly restored at 7 days post stroke, when numerous cortical cells were immunolabeled by BrdU or the mitosis-specific marker phosphorylated histone H3 (Phos-H3). Some of these cells were even doubly immunopositive to the neuron-specific marker Neu N and the astrocyte marker GFAP, as analyzed by 3-D confocal. In adult rats exposed to MCAO, widespread BrdU-immunolabeled cells appeared in the cortex, ipsilateral striatum and dentate gyrus of the hippocampus. Some of which were doubleimmunolabeled by the neuron specific markers Map-2, β-tubulin III and Neu N as analyzed by 3-D confocal. As early as 24h postischemia, BrdU-immunopositive endothelial cells were aligned as microvessels, some of which exhibited distinguishable lumens in the ischemic boundary zone, where VEGF-A, B, C proteins and their receptors flt-1, fik-1, flt-4 were overexpressed at 72h after MCAO.Conclusion: PRS model in adult mice elicits a dynamic deterioration and then restoration of local CBF, CPS, ATP and tissue morphology in the spontaneously reperfused cerebral cortex at 7d after stroke, where cortical neurogenesis and gliosis occurred. In adult rats with MCAO, neurogenesis occurred at 30 and 60d in the penumbral cortex and striatum. Angiogenesis occurred as early as 24h, which contributed to the spontaneous reperfusion frequently observed in this setting of acute ischemic stroke.
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39.
  • Jiwakanon, Jatesada (författare)
  • The porcine endosalpinx at different reproductive stages : morphology, immune cell infiltration and cytokine expression
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Fertilization takes place in the lower part of the porcine oviduct and to be successful, a balance between immunological tolerance to allogeneic differences and immune reactivity to foreign pathogens is required. The thesis aims to describe immune cells and morphological changes in different segments [isthmus (Isth), ampulla (Amp) and infundibulum (Inf)] of the porcine oviduct at various stages of the oestrous cycle, after artificial insemination (AI, pre- and post-ovulatory) and during early pregnancy. The expression of pro-inflammatory and suppressive cytokines was also determined (RT-PCR and immunohistochemistry, IHC) in oviductal samples collected after AI with different components (fresh semen, spermatozoa in extender or extender alone) or only catheter inserted (control) in gilts. In cyclic sows, the epithelial morphology of Amp and Inf varied during the oestrous cycle. High levels of pseudostratification, mitotic activity and secretory granules were found at pro-oestrus/oestrus indicating influence of ovarian hormones. Lymphocytes were predominant in the epithelium whereas both lymphocytes and plasma cells were the major cell types in the connective tissue (CNT). Higher numbers of these cells were found in the Inf than in the Isth both in the cyclic sows and in sows after AI. Neutrophils were found mainly in the infundibular CNT, in cyclic sows at pro-oestrus and in pre-ovulatory inseminated sows in one group (40h after AI). In post-ovulatory inseminated sows, the numbers of neutrophils were lower but present for a longer period. In gilts, IHC-labelling for TGF-β1, IL-10 and IL-6 was apparent, especially in the epithelial cells. Higher mRNA expressions of these cytokines were found in the Isth compared with the Inf and the TGF-β1 mRNA expression was higher than that of IL-6 and IL-10 in both segments. Shortly after AI, no difference between treatments could be detected for any of these cytokines but 35-40 h after AI, the TGF-β1 mRNA expressions were higher in gilts inseminated with different semen components than in the control animals (only catheter inserted). Thus, endogenous production of TGF-β1, IL-10 and IL-6 was indicated and suggests that these cytokines have a physiological function in the porcine oviduct. The relatively higher expression of TGF-β1 mRNA indicates that this cytokine exerts an immunomodulatory role, mainly in the isthmic part of the oviduct, and this seems to be enhanced by AI. The differences between the upper and lower part of the porcine oviduct regarding presence of immune cells and expression of cytokines are likely to reflect a local immune modulation.
  •  
40.
  • Johansson, C. A., et al. (författare)
  • A comparison of experiences of training emergency care in military exercises and competences among conscript nurses with different levels of education
  • 2007
  • Ingår i: Military Medicine. - : Association of Military Surgeons. - 0026-4075 .- 1930-613X. ; 172:10, s. 1046-1052
  • Tidskriftsartikel (refereegranskat)abstract
    • The military emergency care education of nurses is primarily concerned with the treatment of soldiers with combat-related injuries. Even though great progress has been made in military medicine, there is still the pedagogical question of what emergency care education for military nurses should contain and how it should be taught. The aim of this study was to describe and compare experiences of training emergency care in military exercises among conscript nurses with different levels of education. A descriptive study was performed to describe and compare experiences of training emergency care in military exercises among conscript nurses with different levels of education in nursing. There were statistical differences between nurses with general nursing education and nurses with a general nursing education and supplementary education. A reasonable implication of the differences is that the curriculum must be designed differently depending on the educational background of the students. Hence, there is an interaction between background characteristics, e.g., the level of previous education and differences pertaining to clinical experience of the participants, and the impact of the exercise itself.
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41.
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42.
  • Kask, Kristiina, 1971- (författare)
  • Hormones, Mood and Cognition
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Ovarian steroid hormones are neuroactive steroids with widespread actions in the brain, and are thus able to influence mood, behavior and cognition. In this thesis the effects of progesterone withdrawal and the direct effects of the progesterone metabolite allopregnanolone are evaluated. Allopregnanolone, through binding to the GABAA receptor complex, enhances inhibitory neurotransmission, thus exerting anxiolytic, sedative and antiepileptic effects. The acoustic startle response (ASR) is a withdrawal reflex evoked by sudden or noxious auditory stimuli, and can be measured in humans as an eye blink. ASR is significantly increased in several anxiety disorders, and notably also during progesterone withdrawal. Sensorimotor gating can be assessed by measuring prepulse inhibition of the startle response (PPI). The CNS circuits regulating PPI are sensitive to hormone fluctuations. GABAergic drugs are involved in cognitive impairment and animal studies have indicated that allopregnanolone may inhibit learning.The main purpose of this research was to evaluate the behavioral effects of progesterone withdrawal on the startle response and sensorimotor gating in PMDD patients and healthy controls, in healthy third trimester pregnant women and healthy postpartum women. A second aim was to evaluate allopregnanolone effects on memory and cognition in healthy women and also on the startle response and PPI. We found that PMDD patients have an increased startle response across the menstrual cycle and a deficiency in sensorimotor gating during the late luteal phase. Ovarian steroids affect sensorimotor gating; pregnant women have lower levels of PPI than late postpartum women. Acutely administered allopregnanolone did not affect the ASR or PPI. Allopregnanolone impairs episodic memory in healthy women.In conclusion, our studies suggest that ovarian steroids, including allopregnanolone, do not influence the startle response. Ovarian steroids affect sensorimotor gating; pregnancy, a condition with high levels of ovarian steroids, suppresses PPI. Theoretically, the variability in PPI across reproductive events is due to effects mediated by the progesterone or estradiol receptors but is not mediated by allopregnanolone. PMDD patients display decreased PPI during the late luteal phase, suggesting underlying pathophysiology in common with other anxiety disorders. The most vulnerable memory system, the episodic memory, is impaired by the allopregnanolone in healthy women.
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43.
  • Kindahl, Hans (författare)
  • Epidemiological study of bovine brucellosis in three agro-ecological areas of central Oromiya, Ethiopia
  • 2009
  • Ingår i: Revue Scientifique et Technique- Office International des Epizooties. - 0253-1933 .- 1608-0637. ; 28, s. 933-943
  • Tidskriftsartikel (refereegranskat)abstract
    • Logistic regression analysis revealed that the breed of cattle and the method of disposing of aborted foetuses and foetal membranes had a statistically significant effect on individual animal seroprevalence (p < 0.05). In lowland areas, the breed (p < 0.05), animal management system (p < 0.05), mating method <0.05), herd size (p < 0.05) and source of replacement stock (p < 0.05) all had significant effects on individual animal seroprevalence.
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44.
  • Klasson, Anna, 1973- (författare)
  • MRI Contrast Enhancement using Gd2O3 Nanoparticles
  • 2008
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • There is an increasing interest for nanomaterials in biomedical applications and in this work, nanoparticles of gadolinium oxide (Gd2O3) have been investigated as a novel contrast agent for Magnetic Resonance Imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were also investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI.Results show that in aqueous solutions, there is a twofold increase in relaxivity for Gd2O3 compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T1 effect and a distinct increase in signal intensity in T1-mapped images. Fluorescent studies show that the Gd2O3 nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as a multimodal contrast agent.This study shows that Gd2O3 nanoparticles possess excellent relaxation properties that are retained in more biological environments. Gd2O3 particles are suitable as a T1 contrast agent, but seem also be adequate for T2 enhancement in for instance cell labeling experiments.
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45.
  • Kokkinakis, Dimitrios, 1965 (författare)
  • Shallow Features for Differentiating Disease-Treatment Relations using Supervised Learning, a pilot study
  • 2009
  • Ingår i: Proceedings of the 12th International Conference TSD (Text, Speech and Dialogue). Springer Verlag, LNCS/LNAI series.. ; 5729, s. 395-402
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Clinical narratives provide an information rich, nearly unexplored corpus of evidential knowledge that is considered as a challenge for practitioners in the language technology field, particularly because of the nature of the texts (excessive use of terminology, abbreviations, orthographic term variation), the significant opportunities for clinical research that such material can provide and the potentially broad impact that clinical findings may have in every day life. It is therefore recognized that the capability to automatically extract key concepts and their relationships from such data will allow systems to properly understand the content and knowledge embedded in the free text which can be of great value for applications such as information extraction and question & answering. This paper gives a brief presentation of such textual data and its semantic annotation, and discuss the set of semantic relations that can be observed between diseases and treatments in the sample. The problem is then designed as a machine learning task in which the relations are tried to be learned in a supervised fashion, using pre-annotated data. The challenges designing the problem and empirical results are presented.
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46.
  • Lindström, Meta, 1941- (författare)
  • Gynekologer och barnmorskor inom svensk abortvård : åsikter, erfarenheter och upplevelser
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Aim: To investigate gynecologists’ and midwives’ views and experiences regarding work in abortion care in Sweden. Methods: Questionnaire to gynecologists (n=269) and midwives (n=258 comprising 48 questions, response 85%. The quantitative studies (articles I-III) were supplemented by a qualitative study (article IV), consisting of focus-group interviews with gynecologists and midwives/nurses. Results: From the questionnaire studies it was apparent that all the gynecologists had worked in abortion care, whilst not all midwives had done so. The male gynecologists were older than both their female colleagues and the midwives; they had most years of experience but were now working least with abortion patients. Both groups considered it absolutely right, that Sweden have legal abortion and that the law was being followed. Most thought that women should be allowed to have an abortion even after they had felt fetal movements. The midwives were generally somewhat more restrictive than the gynecologists. Half of all thought that the work with abortion patients brought something positive with it. Those having worked longest and most extensively, especially during the previous year were most liberal. Both groups felt that there was a difference between working with surgical and late abortions compared with medical abortions. One in four had had misgivings when involved in surgical and medical abortions, and one in two with abortions after the 18th week. All were positive about the transition to medical abortions, and roughly two thirds of the midwives thought that the primary care sector should be able to take care of these, whereas less than half of the gynecologists thought this. The majority considered it important to receive further and continuing professional development and ongoing guidance. From the focus-group interviews it was clear that the experiences of the gynecologists were largely connected with the technical development of abortion methods and those of the midwives/nurses with improved pain relief. The work was sometimes described in paradoxical terms and was occasionally experienced as frustrating, especially in connection with repeat abortions. Neither of the two groups, however, had had any doubts about participating in abortion. The gynecologists described how women now expected to get an abortion, whereas previously they had asked for one. The midwife/nurse group maintained that the meetings with the women had become considerably more frequent. The interaction between the two professional groups was marked by great trust in each other’s professional competence. Conclusions: Gynecologists and midwives working in abortion care support Swedish abortion legislation and have no doubts about participating in abortions, despite the fact that they have frequently experienced complex and difficult work situations. The character of the work is experienced as contradictory and frustrating, but also as challenging and rewarding. The awareness that the two professional groups have of the importance of continuing professional development and ongoing guidance should be acted on. Furthermore, their collective views and experiences should be made use of, so that abortion care can be developed, not only in order to promote women’s health, but also to improve the work environment for the abortion staff.
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47.
  • Liu, Yuanhua, 1971, et al. (författare)
  • Usability Tests as a Benchmarking Tool - A Case Study on Complex Medical Ventilators
  • 2009
  • Ingår i: Contemporary Ergonomics 2009. - 9780415804332 ; , s. 182-188
  • Konferensbidrag (refereegranskat)abstract
    • Medical ergonomics has become an important topic in the field of ergonomics due to the increasing deficiencies in medical device design. The aim of the present study was to use usability testing as a benchmarking tool of modern and complex ventilator machines in a real hospital setting to propose future redesign ideas for a target machine – SERVO-i. A usability study was carried out at the neonatal intensive care unit (ICU) with 6 expert nurses. During the tests, an artificial lung was used to simulate the real treatment context on a neonatal patient. A number of potential usability problems were detected on SERVO-i. Using Babylog and Stephanie as two reference machines, the strengths and weaknesses of SERVO-i were identified as well. Some valuable lessons were learnt from the study, which could be used as guidance for the choice of test subjects and control of tests in real life human-machine working environments.
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48.
  • Lundgren, Magdalena, 1973- (författare)
  • Interplay between hormones, nutrients and adipose depots in the regulation of insulin sensitivity : an experimental study in rat and human adipocytes
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Obesity and specifically central obesity is related to insulin resistance, type 2 diabetes and other components of the so-called metabolic syndrome. The aim of this study was to elucidate the interplay between hormones, nutrients and adipose depots in normal and insulin-resistant fat cell metabolism.High levels of free fatty acids (FFAs) induce insulin resistance in muscle and liver in vivo. In the present study, rat adipocytes were treated with high physiological levels of oleic or palmitic acid in vitro for 4-24 h. This treatment had no effect on basal or insulin-stimulated glucose uptake capacity in these cells, neither did it affect the levels of the insulin signalling proteins; insulin receptor substrate (IRS)-1 or –2, phosphatidylinositol 3-kinase (PI3-K), protein kinase B (PKB) or glucose transporter (GLUT) 4, or the regulation of lipolysis rate.Visceral adiposity is considered to be more harmful than peripheral adiposity with respect to metabolic and cardiovascular complications. In adipose biopsies from subjects undergoing abdominal surgery, we found that glucose uptake capacity was elevated in omental as compared to subcutaneous adipocytes. The sensitivity (EC50) or maximum relative response to insulin, measured as % of basal, did however not differ between the depots. In women, subcutaneous adipocytes displayed a higher lipolysis rate following cAMP-stimulation than omental adipocytes, whereas there was a tendency towards the opposite in adipocytes from men. No differences were found between depots or sexes in the ability of insulin to inhibit lipolysis or in the levels of the lipolysis regulating proteins, i.e. protein kinase A (PKA), hormone sensitive lipase (HSL) and perilipin.Glucocorticoids, e.g. cortisol, exert pronounced insulin-antagonistic effects and are associated with redistribution of fat from peripheral to central fat depots in humans. Treatment of human subcutaneous and omental adipocytes in vitro, with the cortisol analogue dexamethasone, resulted in a dose dependent down-regulation of basal and insulin-stimulated glucose uptake capacity in omental, but not in subcutaneous cells. Concomitantly, the levels of IRS-1 and PKB were decreased only in omental adipocytes after dexamethasone treatment. The relative effect of insulin to stimulate glucose uptake was however not altered by dexamethasone treatment. The cAMP-stimulated lipolysis rate was elevated by dexamethasone treatment in cells from the subcutaneous depot in women and tended to be elevated in omental cells from men. No alterations however, were seen in the levels of the assessed lipolysis regulating proteins.Subcutaneous as well as omental fat cell size correlated negatively to insulin action in subcutaneous fat cells in vitro after adjusting for age, sex and body fat parameters in non-diabetic, but not in type 2 diabetic, subjects. Large subcutaneous fat cell size was strongly related to plasma leptin levels in non-diabetic and in type 2 diabetic subjects.We conclude that 1) adipocytes seem to be less vulnerable to elevated levels of fatty acids than muscle and liver cells, 2) the interactions between glucocorticoids and insulin in the regulation of glucose uptake differ between adipose depots, 3) depot specific hormonal lipolysis regulation differs between sexes and 4) fat cell size is related to insulin action in subcutaneous fat cells and to circulating levels of leptin.
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49.
  • Midhagen, Gunnar, 1953- (författare)
  • Adult Coeliac Disease in Clinical Practice
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Coeliac disease (CD) is considered to be the result of a complex interplay of intrinsic (genetic) factors and variable extrinsic (environmental) factors. The complex background of CD explains its wide spectrum of clinical manifestations. For a very long time CD was considered more or less a disease of childhood, which was extremely rare in adults. Nowadays we know that CD is one of the most common food intolerance disorders.An epidemiological study of CD in a geographically defined area of Sweden (Paper1) showed a prevalence of 95.5/ 100 000 inhabitants. Among the associated diseases an especially high incidence of associated thyroid disease, 10.8% was observed.In a fifteen-year cohort follow up study of all CD-patients residing in the counties of Örebro and Linköping (Paper 2) the total mortality was increased with 38% (SMR 1.38 95% C.I. 0.31-0.83). This was mainly explained by a 48% increased death rate in ischemic heart disease, significant in patients over 65 years (SMR 1.58 95% C.I. 1.00-2.06). However, there was a 47 % lower risk of all malignancies (SIR 0.53 95% C.I. 0.31-0.83).A cohort of 22 consecutively biopsy-proven adult CD patients (Paper 3), were followed in respect of antibody titres from diagnosis and after 1, 3, 6, and 12 months on a gluten free diet (GFD). All antibody titres fell sharply within one month. Thus excluding a CD diagnosis serologically on a patient who has initiated a GFD by herself is not to recommend.In another cohort with CD patients (Paper IV) who were diagnosed 8-12 years earlier recommended and who were recommended, the reliability of diet history, serological and biochemical markers to predict the appearance of the small intestinal mucosa were analysed (Paper IV). The history of a strict GFD gave a predictive value of 88% of a mucosa in remission. The values of serological tests (AGA, EmA and tTG) to predict a mucosa in remission were 93% for all.In CD patients in remission gastro-intestinal symptoms were evaluated with the GSRS questionnaire. Subjects with CD reported significantly more GI-symptoms than a general population sample (p<0.01). This was particularly true for women with CD who scored worse than female controls .By contrast men with CD reported no more symptoms than male controls.
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50.
  • Nilsson, Andreas, 1973- (författare)
  • Physical activity assessed by accelerometry in children
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Physical activity (PA) is likely to constitute an important aspect of health-related behaviour in growing children. However, the knowledge on levels and patterns of PA in children is limited, due to the difficulty of precisely measuring this complex behaviour in normal daily living. Information on variables that significantly contributes to the variability in PA patterns is warranted as it may inform strategies for promoting physically active lifestyles in school-age youth. The overall purpose of the present studies was to increase the knowledge about the use of accelerometry when assessing PA in children, and examine sources of variability in objectively assessed PA behaviour in children. The study samples included 1954 nine- and 15-year-old children from four geographical locations in Europe (Norway, Denmark, Estonia and Portugal), and additionally 16 Swedish seven-year-old boys and girls. PA was assessed by the MTI accelerometer during free-living conditions, including both weekdays and weekend days. A part of the PA assessment was conducted using different time sampling intervals (epochs). Predictions of estimates of daily energy expenditure from accelerometer output were calculated using previously published equations. Potential correlates of PA behaviour were assessed by self-report. The main findings were; a) the epoch setting had a significant effect when interpreting time spent at higher intensities of PA in young children, b) predicted energy expenditure differed substantially between equations, c) between- and within-day differences in overall levels of PA, time spent at moderate-to-vigorous intensity physical activity and time spent sedentary differed between age, gender and geographical location, d) outdoor play and sports participation were differentially associated with objectively measured PA in 9- and 15-year-old children. It is concluded that the sporadic nature of children’s physical activity require very short epoch settings for detecting high intensity PA, and that different published equations for estimations of daily energy expenditure cannot be used interchangeably. The interpretations of average energy expenditure from available equations should be made with caution. Based on a large sample of children of different ages, weekend days and leisure time during weekdays seem appropriate targets when promoting PA in order to increase the proportion of children achieving current recommendations on health enhancing PA. Further, significant correlates of PA behaviour dependent on age group are presented, which should be considered when planning interventions for promoting PA in school-age youth.
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