| 11. |
- Gregersen, Nils-Petter, 1950-
(författare)
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Prevention of road accidents among young novice car drivers
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis presents five different studies with the overall purpose of developing better preconditions for preventing accidents among young novice drivers. Too many young drivers are killed or injured in road accidents all over the world and we have still not succeeded in reducing their overrisk and fully understanding the interaction between the processes behind their accident involvement. The focus of the thesis is on the development of a model of the behaviour of young drivers in which different factors contributing to their accident involvement are explained. In the first study, new strategies in driver training have been developed and experimentally tested, the aim being to reduce the problems of overestimation, poor visual search patterns and unstructured teaching and training by laymen (I). In the second study, different safety measures were developed and experimentally tested with the purpose of finding the best method for reducing accidents among professional drivers (II). These two studies, combined with literature surveys, have contributed to the design of the model of young drivers' accident involvement. The suggested model is presented in paper m. The last two studies aim at deeper understanding of two specific relations in the model, the relation between training strategy and young drivers' subjective skill (N) and the relation between lifestyle and accidents (V).The results of these studies, including the literature surveys of paper Ill, underline the complexity of the young driver problem. A structure with three main factors influencing accident involvement is suggested: the learning process, social influence and individual preconditions. Through different processes such as training and subjective skill, feedback and motives for driving, skill acquisition and automation, subjective norms or lifestyle, these factorsinfluence driving behaviour and thereby accident involvement. In the two first studies, it was shown that improved driver training, in spite of poor results from many other evaluations of driver training, may contribute to the prevention of young drivers' accident involvement. It was also found that the strategy that is chosen for driver training is important for the driver's own estimation of his skill. The wrong type of training may produce over-confident drivers.Even if we have considerable knowledge about the factors contributing to accident involvement, we cannot yet with certainty identify the best countermeasures. We need to know more about these processes. Since there are still many unsolved problems and many processes in young driver behaviour that are not understood well enough, there is probably still a large potential for improving safety among young drivers.
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| 12. |
- Gupta, Anil
(författare)
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Aspects of recovery following day care anaesthesia : A clinical and experimental study
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A new test for the assessment of psychomotor recovery - the perceptive accuracy test - was designed and tested in a group of volunteers. It was found to be reproducible and not associated with any significant learning. Two hundred patients (ASA I-ll) undergoing day care arlhroscopic surgery were then studied in order to determine which anaesthetic technique is associated with the best recovery profile. No pharmacological premedication was given to any of the patients. The methodology was standardized in all studies so that the anaesthetic technique was similar between the groups, except for the study dmgs. Postural stability was measured following the injection of midazolam intravenously, using computerized dynamic posturography, Recovery was assessed using a combination of tests including a recovery scale, psychomotor tests and assessment of mood. Discharge times and post-operative complications were also recorded. Results showed that induction of anaesthesia with propofol followed by maintenance with isoflurane in oxygen and air, and alfentanil as analgesic, were associated with a good recovery profile. Maintenance of anaesthesia with propofol instead of isoflurane proved to be a satisfactory alternative. Early recovery was more rapid in patients anaesthetized with desflurane, but this group had a worse overall mood score, and a higher incidence of minor postoperative complications compared to the group in which anaesthesia was based on isoflurane. Postural stability was affected at 45 min after midazolam administration. The perceptive accuracy test was found to be sensitive in the detection of residual effects of anaesthetics, it was not associated with significant 'learning', it was easy to use, and the results obtained were 'on-line' and did not require tedious calculations.In summary, induction of anaesthesia with propofol followed by maintenance with isoflurane in oxygen and air, and alfentanil for analgesia is associated with rapid recovery, minimal post-operative complications and good overall mood scores. total intravenous anaesthesia based on propofol is a suitable alternative. Computerized dynamic posturography is a new method for studying balance disturbances. Perceptive accuracy test is sensitive in the detection of residual effects of anaesthetics but more studies are needed to describe its exact place amongst the battery of psychomotor tests.
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| 13. |
- Gustafsson, Urban
(författare)
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Microcirculation in skeletal muscle during hypoperfusion : An experimental study regarding some psysiological and pharmacological factors influencing blood flow and oxygen pressure distributions
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The vascular bed in skeletal muscle plays an important role in the regulation of the systemic circulation. The present study was undertaken to investigate how capillary blood flow and oxygenation in skeletal muscle are affected by: a) a reduction in the levels of respiratory gases in blood, hypocapnia or hypoxia, and b) the interaction of anesthetics (pentobarbital, propofol, ketamine) during hemorrhage, and c) hypotension induced pharmacologically by adenosine, sodium nitroprusside or acetylcholine.The experiments were performed on the vastus medialis muscle in mechanically ventilated anesthetized rabbits. Skeletal muscle microvascular perfusion was investigated with a local hydrogen clearance technique (LHC) (using a multi wire microelectrode) and laser-Doppler flowmetry (LDF). Skeletal muscle oxygen pressures (Pt02) and pH wereassessed using a multiwire Clark-type oxygen or an antimony (pH) microelectrode.Hypocapnia (arterial PC02 2.3 kPa) decreased LDF flow and Pt02, whereasmuscle tissue pH remained unchanged. This was interpreted as being due to a reduction in microvascular perfllsion induced by vasoconstriction. This led to a decline in both tissue oxygenation and in the removal of acid metabolites, which counteracted a developing tissue alkalosis. Apart form the vasoregulatory role of carbon dioxide, it appears that muscle tissue pH is an important factor in the control of skeletal muscle perfusion. Hypoxia (arterial P02 4.0 kPa) reduced LHC flow and Pt02. This was reversed by the administration of ritanserin (serotonin antagonist), despite a further reduction in blood pressure. This supports the concept that the decline in capillary perfusion during systemic hypoxia is at least partly mediated by serotonin.Hemorrhage was induced by withdrawal of blood to a mean arterial blood pressure of 40 mmHg, and measurements (LHC, LDF) were carried out during the spontaneous recovery period. When ketarnine wa<> used as anesthetic a higher capillary perfusion was found as compared to pentobarbital or propofol. These differences may be mediated, as suggested by the results from other studies, by the cardiovascular stimulating properties of ketamine, the effects on the renin-angiotensin system by pentobarbital and venomotor tone by propofol.Hypotension, 20-25% reduction in mean arterial blood pressure, induced by adenosine, was associated with a decrease in skeletal muscle capillary blood flow and an increase in PtOz. This may be explained by a redistribution of capillary flow and/or a reduction in local oxygen demand. Hypotension induced by sodiuin nitroprusside to a similar level, on the other hand, increased capillary blood flow, mostly in the high flow range, whereas the oxygen pressure distributions were reduced. This may be caused by an increased local oxygen demand. Acetylcholine-induced hypotension decreased capillary blood flow which was most pronounced in the high flow range, while oxygen pressure distributions decreased homogeneously in a manner similar to that seen during hemorrhage.The findings presented rnay be of importance in clinical situations with compromised skeletal muscle circulation.
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| 14. |
- Henriksson, Chris, 1938-
(författare)
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Living with fibromyalgia : A study of the consequences for daily activities
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Fibromyalgia (FM) is a chronic generalized muscle pain syndrome. This thesis is a study of 116 patients with FM, twenty living in the USA and the rest in Sweden, all meeting the classification criteria proposed by the American College of Rheumatology, and 39 patients with chronic regio!Jal muscle pain. The purpose was to explore the consequences of the fibromyalgia syndrome for the activities of daily life. The consequences of the syndrome have, been described from the patients' perspective. Data have been collected through different types of questionnaires, 250 semi-structured diaries, and qualitative analysis of 40 semi-structured interviews. A five-year follow-up study was performed to collect data on changes over time in symptoms and psychosocial consequences.The results show that the fibromyalgia syndrome influences daily life profoundly. Both pain and muscular fatigue are continuous, though there are changes in severity, both during the day and over longer periods. Most activities are difficult to perform, at least over a prolonged period. The time structure of the day is disrupted and most patients have to adjust habits and roles in order to manage their life situation. There is acontradiction between the level of disability experienced by the patients and their healthy and non-disabled appearance. This leads to misunderstandings and influences the selfimage. The results in this thesis indicate the importance of early intervention, where the patient is given information about the condition and support to adjust to the limitations, thus preventing unnecessary disabilities and handicaps from evolving.The comparison between patients with chronic regional muscle pain and fibromyalgia indicates that there is a quantitative, rather than a qualitative, difference between the two conditions.
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| 15. |
- Holmgren-Peterson, Kajsa, 1964-
(författare)
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Structure and dynamics of epithelial cells : Studied with confocal microscopy and flourescence recovery after photobleaching
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Epithelial cells of the human body form a physical barrier to harmful agents and potential invading microorganisms. In the small intestine they must also produce enzymes for digestion of food and be able to absorb nutrients.The aim of this work was to study properties of epithelial cells in model systems using cell lines and toad bladder cells, and to study the effect of gluten intolerance (celiac disease, CD), viz. a pathological condition, on human small-intestine epithelial cells, enterocytes. Fluores-cence microscopy techniques, and primarily confocallaser scanning microscopy (CLSM), have beeen used as the major methods in the investigation. Part of the work has also been to develop, and apply, tools for measurements in confocal rnicroscopy images to obtain semi-quantitative information on structures.Fluorescence recovery after photobleaching (FRAP) was used to study the effect of maturation of small intestine-like epithelial cells. Lateral diffusion of membrane components was measured to reveal alterations in membrane fluidity induced by differentiation. No general effects on the lateral mobility of membrane components was observed, rather distinct effects were noticed on protein diffusion.Vasopressin induces the fusion of vesicles containing water channels with the apical membrane of toad bladder epithelial cells. This fusion is known to result in depolymerization of fllamentous actin (F-actin) of the cell. CLSM was used to assess where in the cell the depolymerization occurs. It was demonstrated that the depolymerization is not evenly distributed, but confined only to the apical region of the cells.In children suffering from celiac disease the mucosa of the small intestine is severely damaged. The damage at the enterocyte level is, however, less investigated. In the present work, CLSM was applied to compare the distributions ofF-actin and of glycoconjugates in enterocytes from children with CD to enterocytes from children not suffering from the disease. The results show that in children with active CD the distribution of both structures was altered, but also that compliance to a gluten-free diet results in the return to normal-looking enterocytes.
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| 16. |
- Jacobsson, Per, 1948-
(författare)
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Skeletal muscle metabolism in patients with severe chronic obstructive pulmonary disease : A study of carbohydrate and fat metabolism
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In chronic obstructive pulmonary disease (COPD) deterioration of skeletal muscle metabolism is reported in both respiratory and non-respiratory muscles. This deterioration may contribute to both the development of respiratory failure and general disability often seen in severe COPD patients. The aim of this study was to obtain more information on carbohydrate and fat metabolism in advanced, stable COPD patients and to investigate the possible association between muscle glycogen and estimates of malnuttition. Furthermore, the effect of long-term oxygen therapy on the metabolic state was studied. Using the needle biopsy technique, muscle specimens were obtained from the quadriceps femoris muscle for analysis of muscle metabolites, glycolytic and oxidative enzyme activities and skeletal muscle fibre composition. Blood fuel metabolites were studied at rest, during exercise and recovery. Lipolysis was studied using a tracer technique and the response of lipolysis to insulin, as well as insulin resistance in peripheral tissues were studied using the euglycaernic, hyperinsulinaernic glucose clamp technique.Depletion of glycogen, A TP and creatine phosphate and increased concentrations of creatine and lactate were observed in the quadriceps femoris muscle. Metabolite concentrations correlated to anerial blood gas values- the lower the Pa02 and the higher the PaC02 the greater the deterioration of the metabolic state. Muscle glycogen concentration correlated to estimates of malnuttition. The correlation between glycogen concentration and prealbumin concentration was strong - the lower the glycogen concentration the lower the prealbumin concentration. After 8 months of long-term oxygen therapy (L TOT) the high energy phosphate state had improved. There was a verylow percentage "oxidative" Type I muscle fibres in the quadriceps femoris muscle. Analysis of enzyme activity also showed adaptation in the form of augmented glycolysis and decreased aerobic metabolism. No changes in enzyme activity were observed after 7 months of LTOT. The turnover rate of free fatty acids (FFA) and plasma FFA concentration were increased in the fasting state. There was a significant positive correlation between turnover rate ofFFA and FFA concentration in arterial plasma. The results also suggest a reduction in the inhibitory effect of inulin on lipolysis. A few hours after a light breakfast FFA, glycerol and 3-hydroxybutyrate concentrations were lower in COPD patients with chronic respiratory failure (CRF) that in COPD patients without CRF at rest, during exercise and recovery, indicating decreased lipolysis in the CRF patients compared to COPD patients without CRF. In patients with severe COPD and muscle glycogen depletion no resistance to insulin in peripheral tissues was observed.In conclusion, skeletal muscle depletion exists in patients with severe, stable COPD. Skeletal muscle glycogen concentration is associated with concentrations of serum proteins. Adaptation of muscle metabolism in the form of augmented glycolysis and reduced aerobic metabolism was observed. Lipolysis is increased in the fasting state and the results suggest a reduction in the inhibitory effect of insulin on lipolysis. No resistance to insulin in peripheral tissues was found. LTOT may improve the muscle energy state of hypoxaemic COPD patients.
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| 17. |
- Jacobsson, Sven-Arne, 1953-
(författare)
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Clinical and experimental studies on total hip arthroplasty
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In a 12-year follow-up study, a low-friction, metal-on-plastic hip prosthetic system (Charnley) was compared with a high-friction, metal-on-metal prosthetic system (McKeeFarrar) in a consecutive series of 169 patients, mean age 67 at the start. Satisfactory results were reported in 92 percent of the patients. One-third of the prostheses showed radiographic signs of loosening. The cumulative aseptic failure rate was 8 percent for the Charnley prosthesis and 15 percent for the MKF prosthesis. The difference was not statistically significant.The performance of a flexible (Bute!) and a rigid (PCA) cementless femoral component was studied in a prospective, randomized study of 28 matched pairs of patients (mean age 52 years). A high rate of stem loosening was observed for the flexible prosthesis and 4 cases of fatigue breakage occurred within the 3- to 5-year follow-up period. Proximal resorption and distal hypertrophy of the femur were frequently noted on the radiographs for the rigid stem. The scintigraphic activity around stems well fixed to bone became normalized in the calcar region. In contrast, it was about 50 percent increased around the prosthetic tip. For loose prostheses, the bony uptake was more intense and did not show the same time-related decrease. The scintimetric results did not correlate well with the signs of bone remodeling seen on the radiographs. Repeated at different time intervals, bone scintimetry may be informative in the followup of noncemented THA.In a consecutive series of THAs, the straight ITI-I stem (n=65), made of titanium alloy, was compared at a 5-year review with the Lubinus femoral component (n=77), curved and made of cobalt-chrome alloy. The ITH stem showed a high frequency of surrounding radiolucent lines. Six of the stems were considered loose as compared with none of the Lubinus stems. To date, 5 have been revised and 2 more are in need of revision operations, all in the ITH group. Although the initial costs were somewhat reduced with the use of the cheaper ITH prosthesis, the estimated accumulated costs turned out to be higher in the ITH than in the Lubinus group due to the increased need for revisions.In a study of THA performed on patients 80 years and older, good pain relief was achieved but at the cost of increased postoperative complications and hospital expenses as compared with patients around 65 years of age at operation. Functional improvement was not as evident as pain alleviation. The procedure did not result in decreased use of welfare services in the elderly group of patients.An experimental study was performed on 10 rabbits. Hydroxyapatite coated titanium plugs were implanted in both femora of each animal. Five were treated for seven days with an NSAID (diclofenac) and five were used as controls, receiving no treatment. A significantly lower force was required to pull out the implants 3 weeks after surgery in the group treated with diclofenac than in the untreated group. The results indicate that even short-term treatment with NSAIDs might interfere with the process of bony ingrowth and thereby endanger primary fixation of the implant despite the presence of a hydroxyapatite coating.A new cementless prosthesis was designed in titanium alloy in order to integrate the principles ofpressfit and flexibility. In a special test set-up the endurance properties of the stem were determined. Prototypes of the prosthesis were subjected to load cycles of 4,000 N in one ·test and to a more physiologic load pattern in another test. In both tests the prostheses broke after approximately 600,000 cycles without showing any material defects. It was concluded that considerable difftculty exists in constructing an "isoelastic" stem with reasonable safety limits to fatigue failure when using titanium alloy.
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| 18. |
- Johansson, Anders
(författare)
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Elimination of circulation IgA and IgS immune complexes : An experimental study in mice, rats and guinea pigs
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Immune complexes were formed between dinitrophenyl- (DNP-) conjugated human serum albumin (HSA) and anti-DNP antibodies (monoclonal mouse IgA or polyclonal rabbit IgG). Blood clearance and tissue distribution of intravenously injected labelled antigen and immunecomplex preparations were studied in mice, rats and guinea pigs. Interaction between immune complexes and liver cells were also studied in vitro. Although neither IgG nor IgA had any great influence on the antigen blood clearance kinetics, both of the antibody preparations had influence on the hepatic uptake. IgG immune complexes were taken up very efficiently by the rat liver and to some extent by the spleen. IgA immune complexes were taken up by the liver in both rats and guinea pigs, although far less efficiently. In rats about 90% of the intravenously injected IgG immune complexes were recovered from the Kupffer cells and 8% from the liver endothelial cells, whereas only minor amounts were found in the hepatocytes. The IgG immune complexes were degraded to about the same relative extent by both Kupffer cells and liver endothelial cells. In vitro the quantitativeuptake and degradation of IgG immune complexes was similar in Kupffer cells and liver endothelial cells. The binding of IgG immune complexes to Kupffer cells and liver endothelial cells was saturable and blocked by preincubation with unlabelled IgG immune complexes, indicating Fc-receptor mediated uptake. Our results suggest that Kupffer cellsnormally eliminate most circulating IgG immune complexes, but that the liver endothelial cells may constitute an important reserve capacity. Also in vitro, the binding ofigG immune complexes by hepatocytes was negligible, and these cells do not seem to be of importance for the handling of IgG immune complexes. Kupffer cells, but not liver endothelial cells, were found to release H202 in response to lgG immune complexes. Further, H202 was found to decrease the association of uncomplexed antigen to both Kupffer cells and liver endothelial cells but had no effect on the association of IgG imrmme complexes in vitro. In vivo, IgA increased the antigen localisation to the hepatocytes in rats, but not in guinea pigs. This difference is probably explained by the fact that rat hepatocytes express the polyIg- receptor on their cell surface, whereas guinea pigs (like man) do not. In both rat and guinea pig circulating IgA immune complexes were, to some extent, taken up by Kupffer cells. In vitro, however, IgA failed to increase the antigen uptake to Kupffer cells from either species. On the contrary, IgA actually decreased the antigen uptake by these cells, and therefore appeared functions as an antiopsonin.
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| 19. |
- Johansson, Agneta
(författare)
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Human mononuclear phagocytes : Production of reactive oxygen species generated by the NADPH oxidase
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human professional phagocytes constitute the first line of defence against invading microorganisms. With a membrane-bound enzyme system, the NADPH oxidase, these cells generate bactericidal metabolites. Activation of NADPH oxidase results in a generation of reactive oxygen species, e.g. superoxide anion and hydrogen peroxide. These oxygen species constitute an important part of the host defence against invading microbes. The subcellular localization of the NADPH oxidase is of great importance, since activation of plasma-membrane-localized oxidase system results in cellular release of potentially hannful oxygen species in the vicinity of the phagocyte. A regulated intracellular store of NADPH oxidase could focus the bactericidal arsenal on the phagocytosed prey and thereby reduce the risk of extracellular release and tissue damage in the host A new technique was developed that allowed measurement of the release, as well as the intracellular generation, of reactive oxygen species. The technique was used to compare the response induced in different types of phagocytic leukocytes, polymorphonuclear neutrophils, monocytes and macrophages. Stimulating neutrophils with the chemoattraclant peptide fMet-Leu-Phe induce an association of the ligand-receptor complex to the cell cytoskeleton. An event that has been suggested to terminate the activation of NADPH oxidase. Termination of the NADPH oxidase actiVity in monocytes occurs without any association of the complex to the cytoskeleton. Obviously, different mechanisms to terminate the fMet-Leu-Phe-induced oxidase response opemte in monocytes and neutrophils. No qualitative difference was observed between neutrophils and monocytes, with respect to the localization of the respiratory burst. However, macrophages lack the intracellular phase of the respiratory burst, and the molecular background of this difference could be identified by using indirect immunofluorescence and subcellular fractionation to localize the membrane component of the oxidase (cytochrome bsss). In neutrophils, most of the cytochrome b558 as well as most of the donnant oxidase activity, was recovered in the specific granules, whereas only a minor part was recovered in the plasma membrane and secretory vesicles. Considering disintegrated macrophages, NADPH oxidase activity was found exclusively in a fraction enriched in plasma membranes. These results indicate that macrophages are incapable of intracellular generation of reactive oxygen species due to the absence of a granule-localized pool of the NADPH oxidase. Despite large similarities between different professional phagocytes, fundamental differences are apparent when comparing structural and regulatory processes related to the NADPH oxidase.
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| 20. |
- Kald, Bengt
(författare)
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Platelet-activating factor, intestinal epithelial cells, and Chron's disease : An experimental study
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Platelet-activating factor (PAF-acethcr, 1-0-alky l-2-acetyl-s n- glycero-3- phosphocholine), is a potent inflammatory mediator that can be formed by a variety of cells and tissues. In the present investigation, the content of PAFacether was determined in mucosal biopsies from the ileum and colon of patients with Crohn's disease and control patients. PAF-acether was found in both groups and was raised in patients with Crohn's disease, both in the ileum and colon.Colonic PAF-accther content was raised irrespective of the presence of colonic inflammation as judged macroscopically. The activity of PAF acetylhydrolase in ileal biopsies was lower in patients with Crohn's disease than in controls, and patients with high disease activity had lower PAF acetylhydrolase activity in plasma than patients in clinical remission or healthy subjects. PAF-acether was also found in small intestinal and colonic mucosa of neonatal rats and was found to decrease as the proportion of epithelial cells decreased during early postnatal development. Cultured intestinal epithelial cells (INT 407 cells) produced PAFaccther when stimulated with calcium ionophorc (A23187) or with phospholipase C from Clostridium perfringens, a naturally occurring bacterial toxin in the intestine. Phospholipase C increased the formation of PAF-acether in INT 407 cells, but did not increase the level of lyso PAF-acethcr. The phospholipase A2 inhibitor 4-bromophcnacyl bromide (BPB) had no significant effect on the PAF- and lysoPAF-acether formation, wheras the calmodulin inhibitor trifluoperazine (TEPA), and the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)- -methyl-piperazine (H-7), decreased the PAF-acether formation, but not the lysoPAF-acether formation. Tumor necrosis factor-alpha (TNA-alpha) potentiated phospholipase A2-mediated release of arachidonic acid (AA), after stimulation with phospholicpase C, withour affecting the formation of PAF-acether.These findings indicate that intestinal epithelial cells are able to produce and metabolize PAF-acether, and that increased PAF-acether formation in INT-407 can be evoked by phospholipase C from Clostridium perfringens , a naturally occuring bacterial toxin. Moreover, the findings add further support to the impirtance of bioactive lipids in inflammatory bowel bowel disease and suggest a possible role for PAF-acether in Croh's disease
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