| 21. |
- Aanesen, Arthur
(författare)
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GABA and human spermatozoa : characterization and regulation of GABA transport proteins
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The present project aimed at investigating the interaction between GABA and human spermatozoa under in vitro conditions. Our initial hypothesis was that human spermatozoa had specific binding proteins for GABA and that the binding of GABA to such binding sites could affect sperm function. Studies on swim-up preparations of human spermatozoa incubated with radiolabelled GABA in the presence of unlabelled GABA, alternatively displacers of GABAA/B receptors and GABA transport proteins, indicated that GABA specific binding sites were present on the surface of human spermatozoa. The potency of the different inhibitors indicated that the binding sites possibly represented GABA transport proteins. No effect on sperm motility or AR was observed following incubation with GABA. Further studies indicated that human spermatozoa are capable of a carrier mediated GABA uptake. The uptake is dependent on the concentration of chloride and sodium in the external medium, and the kinetic properties of the carrier resembled high affinity GABA transport proteins. Uptake of radiolabelled GABA into human spermatozoa in the presence of steroids was investigated. We examined progesterone, other steroids known to increase calcium influx, and steroids known to be ineffective as stimulators of calcium influx in human sperm. The results demonstrated a twofold increase in GABA uptake following preincubation with P or steroids known to stimulate calcium influx. In contrast, an inhibition of GABA uptake following preincubation with activators of protein kinase C was observed. The results suggest a role for PKC in the regulation of GABA transport in human spermatozoa. The reduced GABA uptake following incubation with phorbol esters and diacyl glycerol (DAG) analogues, as well as the lack of effect observed following addition of inactive DAG analogues, strongly indicate such a regulatory pathway. The existence of GABA transporter m-RNA and proteins in human testis and sperm was examined using RT-PCR, immunohistochemistry and immunoblotting. Oligonucleotide primer pairs were designed from nucleotide sequences for the three cloned GABA transport proteins identified in human brain: GAT-1, GAT-3 and BGT-1. From homogenized human testis, PCR products of predicted size and with homology to respective GABA transport proteins were identified. This finding indicates the MRNA expression of all three GABA transporters in human testicular tissue. Studies on the protein expression of GABA transporters in sperm cells were performed with SDS-PAGE and immunoblotting techniques. Immunoblots using polyclonal antibodies raised against rat GAT-1, GAT-2 and GAT-3 recognized bands of approximately 65kDa, indicating cross-reactivity to GABA transporters present in human sperm cells. Pharmacological characterization of GABA uptake with specific inhibitors of GABA transport revealed a unique sequence in the relative potencies of the inhibitors tested. The results may indicate the presence of more than one GABA transporter in the plasma membrane of human spermatozoa. Immunoblots and immunohistochemistry studies indicate the presence of one or several GABA transporters in human spermatozoa and testis, these results are supported by pharmacological studies using specific inhibitors of GABA transport. These studies add new information to the present knowledge concerning GABA and human spermatozoa. They also for the first time describe specific GABA transport proteins in the male reproductive tract. Further studies are however, required to elucidate the functional role for these proteins in terms of human reproduction.
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| 22. |
- Aanestad, Øystein
(författare)
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Quantitative electromyographic studies of the perineal muscles in normal subjects and patients suffering from anal or urinary incontinence
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of the study were to characterize the interference pattern in perineal muscles in healthy subjects with the use of quantitative EMG techniques, to evaluate if prostatic surgery had any effect on the interference pattern and furthermore to examine the interference pattern in the perineal muscles in patients suffering from urinary or anal incontinence.The interference pattern in the perineal muscles was examined with a computerized analysis, the Turns and Amplitude (T/A) analysis, and the innervation pattern of the muscles was examined with single fiber electromyography measuring the fiber density. Reference values were collected from 30 normal subjects. The patient material consisted of 20 males subjected to transurethral prostatectomy (TUR-P), 10 males who underwent radical retropubic prostatectomy (RRP), 20 patients suffering from anal incontinence and 24 women withurinary incontinence.T/A analysis of the interference pattern in the perineal muscles in normal subjects showed a significant increase in number of turns/sec and mean amplitude correlating to increasing force but no age-related changes.TUR-P and RRP did effect the innervation of the distal urethral sphincter muscle as shown by increased fiber density indicating a peripheral nerve lesion. T/A analysis did not shown any increased activation of the distal urethral sphincter as a compensation for the loss in bladder neck sphincter function but rather signs of decreasedcentral activation.Patients with idiopathic faecal incontinence showed signs of impaired innervation of the external anal sphincter muscle. A decreased interference pattern at maximal contraction indicated a reduced central activation of perineal muscles, in particular for patients with partial rupture of the external anal sphincter muscle. The reduced central activation could play a role for the aetiology of faecal incontinence.Patients with urinary stress incontinence also showed signs of impaired innervation of the external anal sphincter muscle as well as reduced interference pattern at maximal contraction and during continuous recording of the EMG activity during cystometry. A reduced central activation of the motor units was predicted as one factor involved in the aetiology.
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| 23. |
- Aardal-Eriksson, Elisabeth
(författare)
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Salivary cortisol and posttraumatic stress reactions : methodological and applied studies before and after trauma
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The field of psychotraumatology has its roots in ancient history. During the past decades, the surveillance of the psychobiological background of reactions to and consequences of traumatic stress has made great progress and the complexity of the human stress response system stands out. The hypothalamic-pituitary-adrenocortical axis activity, modulated by various neuroimmunological substances, seems to play a major role in the stress response. However, there are still inconsistencies in explanations of relationships between biological and psychological changes following traumatic stress. Moreover, the matter of predictive factors for the development of posttraumatic morbidity is still in a speculative phase.The aims of the present thesis were to further develop a commercial serum cortisol radioimmunoassay (RIA) for determination of cortisol in saliva and to test its reliability, specificity and sensitivity as a biochemical assay. The saliva sampling procedures and sample storage stability were also to be tested. Further issues were to investigate determinations of salivary cortisol and serum prolactin in relation to selfratings of posttraumatic psychological distress and general psychological health. Possible predictive and concurrent validity of salivary cortisol as a biochemical marker for posttraumatic psychological distress were to be tested.Cortisol is present in saliva mainly in non-protein form, representing the free, biologically active fraction of the total plasma cortisol concentration. In a first phase of the present thesis, the commercial serum cortisol RIA was modified for determination of cortisol in saliva. The relation between salivary and serum cortisol concentrations was tested. Reference ranges at 8 AM and 10 PM for the salivary cortisol assay were established from 195 healthy subjects. Salivary cortisol concentrations were tested in relation to serum cortisol in estimating adrenocortical function during endocrine dynamic function tests in 37 patients and 13 healthy controls. In testing salivary cortisol as a marker for stress for fieldwork use, a screening study was performed on 66 male rescue workers. Salivary cortisol at 8 AM and 10 PM and serum prolactin were determined and general psychological health and posttraumatic psychological distress were estimated with the self-rating scales General Health Questionnaire, Impact of Event Scale and Posttraumatic Symptom Scale. These scales were used in the second phase of the thesis. Three applied follow-up studies were performed with sampling of salivary cortisol and self-ratings: (a) a study of 31 UN-soldiers five days, two and nine months after a mine accident; (b) a study of 145 UN-soldiers before, at return, and two and six month after a six month mission. (c) a study of 101 UN-soldiers six and twelve months after a six month mission with severe combat exposure.The results from the present thesis indicate that the modified method of salivary cortisol determination possesses sufficient precision, accuracy, sample storage stability and procedural advantages for laboratory, clinical and field application. Moreover, it possesses moderate predictive information and moderate to high concurrent validity as a biochemical marker for posttraumatic psychological distress.
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| 24. |
- Aardal Lönnerfors, Celine
(författare)
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Robot-assisted laparoscopy for benign uterine disease. Feasibility, outcome and hospital cost.
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The introduction of the laparoscope was a milestone within gynecologic surgery. Despite evidence of better perioperative outcome compared to laparotomy, laparoscopy is mostly performed for less advanced surgical procedures and the uptake of laparoscopic hysterectomy has been slow. An effort to preserve the clinical benefits of laparoscopic surgery and facilitate the performance of more advanced surgery has led to the development of robot-assisted laparoscopic surgery. Technical progress has been advantageous for the patient from a historical point of view, but this cannot be assumed without proper evaluation. As for all surgical approaches, it is important to recognize the possible applications of robotic surgery as well as proper patient selection both from a clinical and economical point of view. The overall aim of this thesis was to investigate the possible applications, clinical outcome and hospital cost of robot-assisted laparoscopic surgery for benign uterine disease at a single institution following the introduction of robotic surgery. Study I: Evaluating the first 1000 robotic surgeries performed showed that a surgical robot provides the possibility to offer minimally invasive surgery to a larger patient population with low rates of conversions and intraoperative complications. Study II: 31 women with symptomatic, deep intramural myomas and either otherwise unexplained infertility or myomas with a possible effect on conception had a pregnancy rate following robotic myomectomy of 68%. Study III: All women (n=114) with a BMI ≥ 30 kg/m2 who underwent a simple hysterectomy by robotics or laparotomy during the study period were included. Robot-assisted laparoscopic hysterectomy in obese women was associated with shorter hospital stay, less bleeding, and fewer complications and longer operative time compared to laparotomy although the operative times for morbidly obese women were similar between robotics and laparotomy. Study IV: 122 women planned for minimally invasive hysterectomy for benign disease were randomly allocated to either robot-assisted- or traditional, minimally invasive hysterectomy in a 1:1 proportion with vaginal hysterectomy as a primary choice in the latter. From the perspective of hospital costs, robotic-assisted hysterectomy is not advantageous for treating non-complex benign conditions when a vaginal approach is feasible in a high proportion of patients. A similar hospital cost is attainable for laparoscopy and robotics when the robot is a preexisting investment. Study V: Complication rates in 949 women planned for robotic hysterectomy for malignant (75%) and benign (25%) gynecological disease over an 8-year period with special awareness of complications possibly related to robot specific risk factors. Intraoperative- and postoperative complications and complications possibly related to the robotic approach diminish with training, experience and refinement of practice. Study VI: All women (n=483) undergoing hysterectomy for benign disease during 2013 and 2014. Vaginal hysterectomy was associated with the lowest hospital cost and robotic hysterectomy with the lowest rate of perioperative complications. Procedure-specific proficiency influences outcome. Robotic hysterectomy for benign disease is clinically advantageous and economically feasible in complex cases, when performed by high volume surgeons.
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| 25. |
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| 26. |
- Aare, Cecilia, 1959-
(författare)
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Reportaget som berättelse : En narratologisk undersökning av reportagegenren
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This study is the first dissertation where the genre of reportage (in the U.S. classified as literary journalism) is systematically mapped with the help of narratology. Using tools primarily from structural discourse narratology, the thesis examines, describes and maps written reportages as narratives. Rhetorical and cognitive narratology complement the approach. The investigation rests on two assumptions. Firstly, a reporter’s professional purpose is to report about people and states of affairs outside the reporter herself. This results in a contextual commitment, which leaves traces in the narrative in the form of a textual commitment. The latter is in turn divided into narrative empathy and narrative compassion/sympathy. The thesis highlights the creation of narrative structures and stylistic features in reportages and the overall conclusion is that conceptions about a reporter’s professional purpose in fact do influence the narrativity of the text. Secondly, in contrast to news journalism, reportage is a personal genre that can be considered a directed reality: the content is taken from reality but the form is personal and a consequence of the writing reporter’s choices. The thesis presents a narratological model where the text develops in the interplay between three instances: a director, a narrator (in a first-person reportage a narrating reporter) and experiencing characters (in a first-person reportage including an experiencing reporter). The director should be regarded as a structuring property of the text itself. Part 1 provides a historical background to the reportage genre and the social side of the reporter role. In part 2, narrative characteristics of the genre are explored and defined together with the common roots of reportage and novels within realism and naturalism. Part 3 demonstrates how a contextual commitment can be transformed into a textual commitment. Throughout the dissertation, the director model is used to investigate differences and similarities between subcategories within the genre, sometimes between single texts, sometimes between reportage in general and fictional narrative. In part 4, a typology of reportage is presented. The genre is divided into five types of narration, based on the representational relation between how the physical reporter has collected information and in what ways an experiencing reporter is or is not apparent in the text. The thesis ends with a historicization of consonance and dissonance within the reportage genre. Consonance emphasizes the characters’ “here-and-now” and can be found within a broad, classical tradition of eyewitness reporting. Dissonance emphasizes the narrator’s retrospective perspective and can be found within the modernistic type of American New Journalism and in more experimentally written reportages from the most recent decades. The thesis demonstrates how both these ways of narrating may enable the reader’s narrative empathy with someone else than the experiencing reporter.The analyses and conclusions are mainly based on Swedish reportages from 1819 to 2014. This material is complemented with international reportages from 1903 to 2007, from Norway, Poland, Germany, Great Britain, Italy, Bohemia, Croatia, Belarus and the U.S. Accordingly, the dissertation demonstrates that traditions of reportage are primarily international and that the observations about narrative patterns within the genre are also relevant outside of Sweden.
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| 27. |
- Aare, Magnus, 1974-
(författare)
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Prevention of Head Injuries - focusing Specifically on Oblique Impacts
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The massive number of injuries sustained in trafficaccidents is a growing problem worldwide, especially indeveloping countries. In 1998, more than one million peoplewere killed in traffic accidents worldwide, while about tentimes as many people were injured. Injuries to the centralnervous system and in particular to the headare especiallycritical to human life. This thesis contains five researchpapers looking at head injuries and head protection, proposingnew and more efficient ways of protecting the head, especiallyin traffic accidents.In order to define the national dimensions of the patternsof injuries incurred in motorcycle and moped accidents inSweden, a statistical survey was performed on data spanning a13-year period (Paper A). In Sweden, 27,100 individualsreceived in-patient care for motorcycle and moped accidentinjuries between 1987 and 1999. The motorcycle and moped injuryrate reduced in the second half of the study period, so toowere the total number of days of treatment per year. Males hadeight times the incidence of injuries of females. Head injurieswere the single most frequent diagnosis, followed by fracturesof the lower limbs. Concussion was the most frequent headinjury. These statistics clearly show the need for better headinjury prevention systems.According to the statistics, the most common type of impactto the head in motorcycle and moped accidents is an obliqueimpact. Oblique impacts generate rotations of the head, whichare a common cause of the most severe head injuries. Thereforea new test rig was constructed to reproduce oblique impacts toa helmeted dummy head, simulating those occurring in real lifeaccidents (Paper B). The new test rig was shown to provideuseful data at speeds of up to 50 km/h and with impact anglesvarying from purely tangential to purely radial. Thisinnovative test rig appears to provide an accurate method formeasuring accelerations in oblique impacts to helmets.When testing the performances of motorcycle helmets,discrepancies are usually seen in the test results. In order toevaluate these discrepancies, the finite element method (FEM)was used for simulations of a few oblique helmet impacts (PaperC). Amongthe parameters studied, the coefficients of frictionbetween the impacting surface and the helmet and between thehead and the helmet had the most significant influence on therotational accelerations. Additionally, a thinner andconsequently also weaker shell and a weaker liner, providedbetter protection for the impacts studied.Since there are no generally accepted global injurythresholds for oblique impacts to the human head, a study wasdesigned to propose new injury tolerances accounting for bothtranslations and rotations of the head (Paper D). In thatstudy, FE models of (a) a human head, (b) a Hybrid III dummyhead, and (c) the experimental helmet were used. Differentcriteria were proposed for different impact scenarios. Both thetranslational and the rotational effects were found to beimportant when proposing a predictor equation for the strainlevels experienced by the human brain in simulated impacts tothe head.In order to reduce the level of head injuries in society andto better understand helmet impacts from different aspect, aballistic impact was also studied (Paper E). The effects ofdifferent helmet shell stiffness and different angles ofimpacts were simulated. In this study, the same FE head modelfrom Paper D was used, however here it was protected with amodel of a composite ballistic helmet. It was concluded thatthe helmet shell should be stiff enough to prevent the insideof the shell from striking the skull, and that the strainsarising in the brain tissue were higher for some obliqueimpacts than for purely radial ones.In conclusion, this thesis describes the injury pattern ofmotorcycle and moped accidents in Sweden. This thesis showsthat the injuries sustained from these accidents can bereduced. In order to study both translational as well asrotational impacts, a new laboratory test rig was designed. Byusing the finite element method, it is possible to simulaterealistic impacts to the head and also to predict how severehead injuries may potentially be prevented.
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| 28. |
- Aare, Sudhakar Reddy, 1978-
(författare)
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Intensive Care Unit Muscle Wasting : Skeletal Muscle Phenotype and Underlying Molecular Mechanisms
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Acute quadriplegic myopathy (AQM), or critical illness myopathy, is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients characterized by generalized muscle wasting and weakness of limb and trunk muscles. A preferential loss of the thick filament protein myosin is considered pathognomonic of this disorder, but the myosin loss is observed relatively late during the disease progression. In attempt to explore the potential role of factors considered triggering AQM in sedated mechanically ventilated (MV) ICU patients, we have studied the early effects, prior to the myosin loss, of neuromuscular blockade (NMB), corticosteroids (CS) and sepsis separate or in combination in a porcine experimental ICU model. Specific interest has been focused on skeletal muscle gene/protein expression and regulation of muscle contraction at the muscle fiber level. This project aims at improving our understanding of the molecular mechanisms underlying muscle specific differences in response to the ICU intervention and the role played by the different triggering factors.The sparing of masticatory muscle fiber function was coupled to an up-regulation of heat shock protein genes and down-regulation of myostatin are suggested to be key factors in the relative sparing of masticatory muscles. Up-regulation of chemokine activity genes and down-regulation of heat shock protein genes play a significant role in the limb muscle dysfunction associated with sepsis. The effects of corticosteroids in the development of limb muscle weakness reveals up-regulation of kinase activity and transcriptional regulation genes and the down-regulation of heat shock protein, sarcomeric, cytoskeletal and oxidative stress responsive genes. In contrast to limb and craniofacial muscles, the respiratory diaphragm muscle responded differently to the different triggering factors. MV itself appears to play a major role for the diaphragm muscle dysfunction. By targeting these genes, future experiments can give an insight into the development of innovative treatments expected at protecting muscle mass and function in critically ill ICU patients.
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| 29. |
- Aarne, Päivikki
(författare)
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Self and other : socio-emotional aspects of development in children with language impairment
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis comprises four studies that focus on young children with language impairment (LI). The research focus was different aspects of socio-emotional development. In Study I visual check back behaviors were investigated in ten pre-school-aged children with LI and in two groups of children with typical development (TD); ten children that were matched with regard to age (AMC) and ten children matched with regard to language level (LMC). Play setting situations were designed to elicit the target behaviors of shared attention, intention and emotion. The children with lower language level (LI and LMC) gave visual check back significantly more seldom than children with a higher language level (AMC). In Study II, the association between communication and language level, and socio-emotional level was investigated by parent ratings. Pre-school-aged children with LI and children with TD were assessed by their respective parents using The MacArthur Communicative Development Inventories (Swedish version (SECDI) and Greenspan Socio Emotional Growth Chart, (GSEGC). An association between language and socio-emotional development was found. Children with LI were rated similar to the young language-matched children with TD, but significantly lower relative to age-matched TD children, particularly concerning symbolic stages of development. In Study III, a case study, the capacity to mentalize was explored in a primary-school-aged boy with a history of LI. In play situations, the child was presented story stems that he could complete by play actions or verbally. The mentalizing capacity was analyzed with respect to the organization and the content of his responses, as well as his observable behavior in the situation. The child had difficulties in affect regulation, i.e. self-oriented mentalizing, and his other-oriented mentalizing was limited as well. In Study IV, parental stress and the parents’ perception of their child’s behavioral as well as communication and language difficulties were investigated by Swedish Parenthood Stress Questionnaire (SPSQ), Swedish version of Strengths and Difficulties Questionnaire (SDQ-Swe) and the Swedish version of MacArthur Communicative Developmental Inventories (SECDI), in three groups of pre-school-aged children: children with LI, children with more extensive communication difficulties and suspected ASD (COM), and children with TD. Parental experience of stress differed significantly between the groups on total and specific aspects of stress. A significant association was found between parental stress and children’s behavioral difficulties in the total group, but not in the clinical groups. Parental stress and children’s communication and language difficulties were associated in the group COM with extensive communication difficulties.
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| 30. |
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