| 61. |
- Foldevi, Mats, 1952-
(författare)
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Implementation and evaluation of problem-based learning in general practice.
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Faculty of Health Sciences, Linköping, Sweden, started the reformedmedical curriculum in 1986. Problem-based Learning as an educational method was introduced into the entire curriculum. It was a response to requests for community-orientation by increasing the involvement of general practice. A new extensive communication skills training - the 'Strand', a new form of examination- 'phase examination', and recurrent clerkships in general practice in the clinical phase were also introduced. The medical cuniculum, with its focus on general practice, together with these innovations are presented in a case report of its implementation and development.The similarities between quality assurance and problem-based learning, as processes and methods, are also identified, described and discussed.Two of the innovations where general practice is a main contributor, namely, the clerkships in general practice and the phase examination 1 and 2 have been evaluated. Of the 115 students, in semester six to nine in the autumn of 1992, 74% filled in the clerkship evaluation questionnaire. The overall rating was very positive. Regression analysis of the rated variables showed that the quality of the tutoring was the strongest determinator of the overall rating. No decline in the students' ratings in the latter semesters was found.A qualitative study was made on all free comments made by the same study group in the same questionnaires. This study identified an area not covered in the quantitative evaluation, the important elements of the student-tutor relationship.The 'phase examinations' have been found to be a valid assessment ofcommunication skills, integrative knowledge and the search for scientificinformation. The use of general practitioners as assessors has strengthened the role of general practice in the curriculum.
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| 62. |
- Follin, Per, 1953-
(författare)
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The primed neutrophil : a friend or a foe in inflammation
- 1991
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human neutrophils are the most abundant of the white blood cells in circulation and represent the first line of defense against invading microorganisms. With a membrane-bound enzyme system (the NADPH oxidase), these cells can generate reactive oxygen metabolites that serve efficiently in antimicrobial defense. Neutrophils are normally dormant in the circulation but may become primed; in that state they can produce an enhanced respiratory burst response upon activation and thereby strengthen the immune response. During bacterial infections, endogenous inflammatory mediators orbacterial products induce metabolic priming of neutrophils, which thenexpose an increased number of receptors to the peptide f-Meth-Leu-Phe(fMLP). There is, however, no correlation between the increased level ofrespiratory burst response and the level of receptor upregulation, indicating that post-receptor events in the activation sequence are also involved. Neutrophils isolated from an inflammatory focus were found tobe metabolically deactivated as far as the agonists NAP-1/IL 8 and C5awere concerned but primed in relation to tMLP. Further characterizationof exudated cells revealed that the mechanism of priming involves protein kinase C but not a rise in intracellular Ca2+ or a decreased inactivation rate of the oxidase. In primed cells most of the increased production of reactive oxygen species induced by fMLP is located intracellularly, whereas, an increased extracellular release of reactive oxygen species occurs during phagocytosis. The fact that primed cells can both produce and, under certain conditions, release increased amounts of hydrogen peroxide raises the question of whether the primed cell is a friend or a foe in the inflammatory reaction.
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| 63. |
- Forastiere, Francesco
(författare)
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Epidemiologic studies of occupational and environmental exposures and cancer of the lung
- 1994
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In order to study the importance of some less well-known occupational exposures and environmental factors in lung cancer etiology, a series of investigations were conducted in the Latium region of Italy, which includes the city of Rome. Five historical cohort studies were carried out on various occupational groups: power plant workers and merchant seamen with potential exposure to asbestos occupations with exposure to silica dust (silicotics receiving a disability compensation), and occupations withexposure to sulphuric acid mist (soap production workers) and to engine exhaust (taxi drivers). In addition, a case-control study evaluated lung cancer risk among ceramic workers exposed to silica dust, and a correlation study compared lung cancer mortality rates in areas with distinct geological features as a proxy of radon exposure in dwellings. Finally, time trends and geographical differences in lung cancer mortality rates in Italy not due to active smoking (background rates) were estimated to obtain an overall view of the aggregate effect of other factors than active smoking.More or less clearly increased risks of lung cancer mortality were observed in the cohorts of power plant workers (SMR=ol. 8, 95% cr~D.77-3.5;9D~ cr~o.ss-3.2), and merchant seamen (SMR~1.7, 95~ CI=l.l-2. 5) 1 probably mainly due to asbestos. An excess lung cancer risk was detected among ceramic workers (OR=2. 0, 95% CI=l.l-3.5); those ceramic workers with silicosis showed an even higher relative risk (0R=3. 9, 95% CI=l. 8-8.3) . Subjects receiving a disability pension for silicosis in the region were also found to have an increased risk of lung cancer (MOR=1.5; 95% CI=l.l-1.9). There was a suggestion of excess risk of lung cancer among workers in the production of soap (SMR=1.7; 95%CI~D.55-3.9; 90~ CI~0.73-3.6), although the limited size of the study precludes any definitive conclusion. Taxi drivers in Rome also appeared to have a slightly increased risk of lung cancer (SMR~1.2, 95~ CI~D.97-1.5), especially those enrolled more recently (SMR~1.4, 95~ CI~l.02-1.9)After adjustment for smoking and urbanization, the ecologic study showed a 20% increase in mortality rates for lung cancer in an area with a higher level of background radiation. Indoor radon exposure may be suggested as a potentially important risk factor for lung cancer in that area.When differences of time and place in lung cancer death rates not attributable to active smoking were studied, all calculations indicated that the estimated background rates increased in Italy from the period 1956-58 to the period 1987-1989, especially in males. Higher background rates were observed in heavily urbanized areas than in rural areas.The overwhelming role in cigarette smoking is well recognized but various environmental factors also play an important role in causing lung cancer. These factors should not be neglected in public health efforts to reduce the risk of lung cancer, especially as they may at times be easier to reduce or eliminate than smoking.
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| 64. |
- Forslund, Tony, 1956-
(författare)
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Nitric oxide modulates neutrophil function
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An important role of the neutrophils is to attack and destroy microbial intruders. In order to do so, these leukocytes must adhere to the blood vessel wall, pass through the endothelial cell layer, move through the tissues to the point of infection, ingest the intruder and destroy it.The aim of this thesis was to study the effects of nitric oxide (NO) on the different steps in the inflammatory response of the neutrophil.Adhesion to a collagen surface was decreased by pretreatment with a NO-releasing substance, and this was mimicked by pretreatment with a functional cGMP-analogue, indicating a role of the NO/cGMP pathway. Homotypic adhesion, aggregation, was not affected by external NO, but when the precursor of endogenous NO-production CLarginine) was added, the aggregation increased. Measurements of total F-actin content in cells showed that a NO-releasing substance decreased the total amount of F-actin, while cGMP increased it. Treatment with L-arginine had no effect.Phagocytosis was neither affected by endogenous NO, nor by a NO-releasing substance. However, if the prey itself released NO, both the adhesion to and phagocytosis of the target was decreased. This NO-particle also inhibited the production of oxygen metabolites, as measured using Luminal-dependent chemiluminescence. The inhibition was almost exclusively affecting the intracellular production of oxygen metabolites, as could be seen when neutrophils were stimulated with FMLP or PMA after an incubation with the NO-releasing particles.Treatment of neutrophils with the NO-releasing substance nitroprusside resulted in a decrease of the respiratory burst. It was primarily the extracellular release that was diminished. This effect can be explained by an inhibition of the enzyme producing oxygen metabolites. Endogenous NO-production increased the chemiluminescence whereas an inhibitor of the NO-synthase decreased it. A possible explanation for these effects is an NO-inhibition of the protection against hydrogen peroxide, i.e. catalase activity, resulting in an increased amount of oxygen metabolites.In conclusion, these results shows that NO has different effects depending on where it is produced and in what quantities. It modulates the different steps of the inflammatory response of neutrophils. Control of NO-formation could therefore be a way to control inflammation.
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| 65. |
- Fredriksson, Mats
(författare)
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Epidemiological studies on colorectal cancer : Some design issues and analytical considerations
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Determinants of colon and rectal cancer have been studied in two case-control data sets, one from the north of Sweden, i.e., Norrland, and the other from the county of Östergötland. In the studies carried out, the main interest was focused on occupational aspects, but diet, medication and earlier diseases were also considered, including a detailed interview regarding diet for a sample of the subjects in Östergötland.A main finding was an association between sedentary work and an increased risk of colon cancer whereas a decreased risk was seen for rectal cancer. Forestry and agricultural work was associated with a reduced risk. Railway employees had an increased risk in Norrland and a tendency to increased risk in Östergötland. Among specific exposures, asbestos was associated with an increased risk. Rectal cancer did not share any of these factors except for a decreased risk for forestry work. The main finding regarding rectal cancer was an increased risk for painters who sanded walls before painting. It seems as occupational exposures influence the risk of colon and rectal cancer in different ways.Regarding diet, reduced risks was seen for daily intake of cheese and to some extent for fiber rich diet. In Östergötland, a protective effect was seen for calcium and cereal fiber on colon cancer. Tea was associated with a reduced risk, whereas coffee or alcohol did not show any association. Increased risk was found for smoked food. Fiber had a protective effect on rectal cancer, whereas alcohol appeared as a strong risk factor.The Norrland study was also analyzed regarding drug intake and other diseases than cancer. In particular, increased risks was associated with iron and verapamil medication. No effect was seen regarding acetylsalicylic drugs. Ulcerative colitis appeared as a strong risk factor and other determinants of risk were cholecystectomy and hyperplasia oftl1e prostate. Appendectomy was associated with a decreased risk.Information regarding inactivation of the tumor suppressor gene p53 was available for some cases in the Östergötland study, providing for a new approach by means of a case-control analysis. High intake of alcohol andthe use of hydralazine-containing drugs were associated with an inactivated gene, whereas iron medication and familial colorectal cancer were not. The results indicate that dividing the cases in subgroups based on molecular biology may reveal more specific associations between exposure and subgroups of colorectal cancer.Some variables were further analyzed in order to check if there would be any gain in using time or intensity as an effect variable as compared to a crude exposure variable. Considering design issues and data analysis, it was found that if a crude determinant indicates that there is an association, then a more in-depth analysis by using time or intensity variables might be worthwhile. A simple method for categorizing continuous variables was also demonstrated. Furthermore, a more thorough analysis of the association between dietary fat and physical activity indicated an interaction between low physical activity and high intake of fat.Validity aspects were critically discussed in relation to the studies. Selection and information bias were found unlikely to have occurred in the kind of data at hand and neither differential nor non-differential misclassification should be a serious problem. Confounding, including combinations wiih misclassification, was considered, in relation to the studies, but with the methods used such a phenomena is less likely to have influenced the results.
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| 66. |
- Frennesson, Christina, 1949-
(författare)
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Age-related maculopathy and macular degeneration : New diagnostic and therapeutic procedures
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Age-related maculopathy (ARM) may progress into age-related macular degeneration (AMD), which is often disastrous to near vision and reading. Currently used treatment is generally not successful in a long-term perspective. Therefore, searching for an early detection of functional disturbances as well as for prophylactic treatment appears important.Colour contrast sensitivity was measured in patients with soft drusen maculopathy (early ARM). No deterioration in visual function was observed with conventional tests. A highly significant elevation (p<0.001-0.0001) of thresholds for all three colour axes was found, indicating an impairment of retinal function. A tendency towards a bimodal distribution was seen, suggesting a subgroup with a more prominent decrease in foveal sensitivity and possibly at higher risk of progression into the exudative form of the disease. Colour contrast sensitivity appears to be a more sensitive measure of early functional disturbances of the retina than provided by the currently used tests.Contrast sensitivity was measured peripheral to an absolute central scotoma in patients with AMD and was found to be significantly lower (p<0.001) than In normals at the same degree of eccentricity. This finding may explain the variations in the need for magnification in low vision patients with identical visual acuity for achieving the same visual performance.A new system for evaluating paramacular function and establishing the most suitable area for eccentric viewing was designed. The method facilitates the procedure of teaching and training the patient to use the eccentric viewing technique successfully. Reading speed increased significantly (pIn a prospective, randomised study, patients with early ARM were treated with green argon laser photocoagulation perifoveally over the drusen area. Parameters such as visual acuity, colour contrast sensitivity and central visual field were unchanged at the 12-month follow-up. The total drusen area decreased significantly (p<0.0001) after laser photocoagulation over a period of 12 mOnths. No complications were noticed. In a matched control group, the area of drusen tended to increase, and there was a significant difference {p
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| 67. |
- Fällman, Maria
(författare)
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Complement receptor-mediated signal transduction in human neutrophils : A role for protein kinase C in the phagocytic process
- 1992
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The neutrophil granulocyte comprises the first line of human defense against invading microorganisms. A versatile motile machinery enables the cell to migrate to the inflammatory site and there engulf and destroy the pathogens by phagocytosis. Engulfment is facilitated by opsonization of the microbes with C3b or C3bi complement fragments or with immunoglobulins, proteins which respectively bind to complement receptors (CRs) and Fe receptors on the neutrophil surface. The aim of the present thesis was to investigate the transmembrane signaling events involved in receptor-mediated engulfment. Experimentially induced inhibition of the phagocytic capacity of human neutrophils could be reversed by pretrcating the cells with protein kinase C (PKC)-activating agents such as PMA and a synthetic diglyceride. This indirectly suggests an important role for PKC in the process of engulfment. Presentation of opsonized yeast particles to neutrophils stimulated the phosphoinositide signaling pathway, resulting in an accumulation of Ins(1,4,5)P3 (IP3) and diglyceride (DG; the endogenous activator of PKC) with a time kinetic correlating that of the cellular uptake of the particles. However, in calcium-depleted neutrophils, formation of IP3 was totally abolished during phagocytosis of complement-opsonized yeast particles, thereby excluding this signal as a regulator of the engulfment process. DG, on the other hand, was still produced in these cells, suggesting a source other than phosphatidylinositols for the generation of this second messenger. Further studies revealed that a major part of CR-mediated DG formation originated from phospholipase D (PLD)-mediated hydrolysis of phosphatidylcholine (PC). The presence of DG suggested a subsequent activation of PKC, which was confirmed by the demonstration of CR-mediated phosphorylation of a well-known PKC substrate, myristoylated alanine-rich C kinase substrate (MARCKS). Moreover, the activity of PLD was shown to be regulated by PKC, which stimulated the production of its own activator by enhancing the activity of the lipase: PKC should thereby be able to maintain its own activity.Furthermore, we could also show that both CRI and CR3 can mediate PLO activation and that the degree of this activation is potentiated by PMA pretreatment and dependent on the fonn of ligand presentation. In conclusion, CR-mediated phagocytosis is associated with PLDmediated hydrolysis of PC and stimulation of PKC, the activity of the latter enzyme appears to be an important regulatory event in the engulfment process.
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| 68. |
- Gadegaard Jensen, Anders
(författare)
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Clinical and laboratory studies on propofol
- 1993
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients undergoing major abdominal surgery were randomly given total intravenous anaesthesia based on propofol and fentanyl, anaesthesia based on propofol, fentanyl and nitrous oxide or anaesthesia based on isoflurane and fentanyl. Postoperative atelectasis demonstrated by computed tomography of the chest was found to a similar extent and a similar decrease in arterial oxygen pressure was seen in the groups. No correlation was seen between the size of atelectasis and postoperative oxygen pressure. Cardiovascular stability was equally well maintained during surgery, but the patients anaesthetized with propofol needed more ephedrine and glycopyrrolate to achieve stability. In all groups the Acute Physiology Score was normal by day I (range 1-7). A similar impairment of bowel function after operation was found, with passage of gas day 3 ( 1-6) and tolerance of enteral intake day 5 (1-10). Hospital stay 11 (6-45) days and incidence of complications were unaffected by anaesthetic technique. Early recovery was similar in the three groups, but patients anaesthetized with propofol reported fewer symptoms, better subjective control and a higher degree of socially orientation than patients anaesthetized with isoflurane. On the whole, the advantages with propofol compared to isoflurane were small, and the addition of nitrous oxide to propofol had no influence on. the results.Laboratory tests on human leucocytes, cultured human glial cells and rat glial cells and neurons were performed with propofol in concentrations between 0.3 ~g·ml" and 50 ~g·ml" (1.7 to 280 ~M). Clinically relevant concentrations of propofol decreased random and chemotactic locomotion of leucocytes in an agarose assay. Concentration dependent and reversible effects of propofol were found on the actin distribution of the cytoskeleton in cultured cells. The maximal effect was seen after 20 min of incubation. Using a single cell microfluorometric method with Fura2 an increase in cytosolic free calcium in rat neurons was seen immediately after the addition of propofol, lasting 128±39 seconds and thereafter returning to normal. This effect was dual, 60-7 5% of the increase came from the extracellular buffer and the remaining part from intracellular stores. A rise in intracellular calcium can lead to changes in the cytoskeleton and to hyperpolarization of a neuron.
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| 69. |
- Gao, Jizong
(författare)
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The Entheses of the Medial Meniscns and Ligaments of the Knee Joint : Descriptive and Experimental Studies
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Meniscal injuries are common in sports. Surgical removal of the meniscus to relieve symptoms is associated with a high risk for late knee joint osteoarthrosis and pain. Meniscal repair or replacement has therefore been advocated. In meniscal replacement procedures proper fixation of the substitute to bone is decisive to guarantee normal meniscal load transmitting function and prevention of osteoarthrosis. Secure fixation of the graft is also essential for the success of ligament reconstruction. Thus, this thesis concentrates on exploration of normal morphology of the insertions of the medial meniscus and other knee ligaments, their ultimate strength and failure mode, and finally the capacity of the meniscal insertion for repair and reconstruction in a rabbit animal model.Extreme mechanical demands are posed on the insertion which connects highly loaded and mobile ligamentous tissue to bone. The abrupt change in tissue stiffness in the insertion is made more gradual by interposition of uncalcified and calcified fibrocartilage tissues of intermediate stiffness between the soft ligament and the hard bone. The thickness of calcified fibrocartilage in an insertion seems to be related to the amount of bending at this site. The interface between calcified fibrocartilage and bone is irregular thereby increasing the contact area between these 2 mechanically different tissues and their resistance to separation; its configuration is individual in each ligament and seems adapted to the loads to which the insertion is subjected. During mechanical testing failures through insertional structures were rare, which confirmed the effectiveness of this tissue configuration. Presence of nerve fibres in meniscal insertional structures suggests sensory function beside the mechanical ones. Hence, all of these specific features need to be reestablished after a reconstructive procedure to ensure adequate insertional function.Transection of meniscal insertions without refixation resulted in repair which after 12 weeks showed tissue differentiation and maturation according to local loading conditions. The repair tissue in the anterior insertion which is mainly loaded in tension acquired ligament-like appearance; in the posterior insertion, which is subjected to compressive, shear and tensile loading, fibrocartilage-like tissue had formed. Calcified and uncalcified fibrocartilages mimicing insertional tissue formed after refixation of the insertion into a bone channel, but a nonnal collagen matrix, interface to bone and mechanical strength did not reestablish.A meniscal insertion healed in prolongated position after transection, and in a case with refixation, it was found partially pulled out. This resulted in both instances in a displacement of the meniscus to the joint periphery and signs for osteoarthrosis similar to what has been found after removal of the meniscus. Thus, despite some capacity of the repair tissue to differenciate and mature to insertionspecific tissue after transection or reconstruction a normal load transmission function of the meniscus probably did not reestablish, and osteoarthrosis was common. Further studies are necessary to improve the fixation of meniscal or ligament substitutes to bone.
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| 70. |
- Garpenholt, Örjan
(författare)
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Vaccination against Haemophilus influenzae type b in Sweden : Aspects of epidemiology, economy and the process of introduction
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Since 1992-1993 vaccination against Haemophilus influenzae type b (Hib) with conjugated vaccines is included in the general Swedish childhood vaccination programme. In this thesis the introduction of Hib vaccination has been evaluated.The epidemiology and clinical spectrum of invasive H. influenzae disease was prospectively studied during the pre-vaccination period in a well-defined population of Sweden 1987-1992. The incidence (cases/100 000/personyear) was 5.9 for all ages and 55 in children 0 to 4 years of age. Serotype b was the dominating type, especially in children. Three patients died in connecting with illness and six developed permanent sequelae.In national studies, the incidence before and after introduction of the Hib vaccination programme was compared. The source for the studies was the report system from the clinical microbiology laboratories to the Swedish Institute of Infectious Disease Control. Already within one year after introduction a decreased incidence was observed. In the prevaccination period the incidence was 34 in 0 to 4 years old children. In 1998 the incidence had decreased to 1.6 in the same age group. Thirteen children were identified with invasive Hib disease in spite of vaccination. Effectiveness, which take in account both direct and indirect effects of vaccination in 0 to 4 years old children was calculated to 96.0% (95 %Cl, 94.2-97.4). To study the impact of Hib vaccination in the on the diagnosis epiglottitis a national register of all patients treated at Swedish hospitals was used. In the age group 0-4 year the incidence decreased with 95 % after introduction of Hib vaccination. Even in older ages a decrease was observed but this trend did not reach statistically significance.An evaluation of the economic consequences of a general childhood vaccination programme against Hib in Sweden was conducted. A retrospective prevaccination annual cohort of 0-4 year old children was compared with an annual cohort of the same age group after a completely implemented vaccination programme against Hib. The cost analysis shows that vaccination against Hib is cost saving when indirect costs are included in the analysis. In the cost-benefit analysis it is shown that society will gain -88 million Swedish Crowns annually when Hib vaccination is totally implemented.The process of introducing general childhood Hib vaccination was studied. The critical factors for implementation of the immunisation programme were found to be the vaccine product, conception of the disease, government economy and public decision-making. Five activity systems were found to be involved in the implementation process, the systems of vaccine production, government administration, news distribution, science, and disease prevention. To structure the results a theoretical framework was used, Culture Historical Activity Theory. The study shows that a broad range of aspects must be considered before an intervention such as a general vaccination programme can be implemented in society.
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