| 1. |
- af Klercker, Tom
(författare)
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Method for inductive case-based decision support system over the Internet : exemplified by ear, nose and throat diagnostics in primary care
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is an example of an ear to loaf process:A Preliminary Essential Data Set (PEDS) for Ear, Nose and Throat (ENT) diagnostics in Primary Health Care (PHC) was established by infologic modelling of existing tractates, between the specialist organisations of ENT and PHC, and four contemporary text-books on the subject (I). The PEDS was then compared to the aggregated data from a sample of case-files from a Swedish PHC centre. The quality of the individual medical record was found to be poor and not sufficient for follow-up and Quality Management (QM) purposes (II). The aggregated data from the case-file sample was processed by an inductive "expert" computer program that generated a decision-tree, based on the total number of decisions (diagnoses) in the data-base. This was nearly identical to the PEDS and somewhat less complicated. Infological modelling of the PEDS and the decision-tree resulted in the proposed Essential Data Set (EDS) for ENT diagnostics in PHC. The decision tree was "pruned" to achieve simplicity and ease of use (III). It was converted into a Computer-aided Decision Support System (CDSS) and put on the Internet using World Wide Web (WWW) tools (IV). This system was then implemented in the Skänninge PHC centre where an Electronic Medical Record System (EMRS) was in everyday use. Due to technical difficulties no integration between the two systems was possible. The CDSS was run on a computer outside the centre and this raised the question of secrecy and security (V). Prior to the implementation, and after a study period of four months attitudes towards, and the acceptance of, new Information Technology (IT) was explored by using focus group methodology (VI). It is important that those who are to use the system are intimately involved in its development. The results showed, that participation of the end-users during implementation is crucial for its acceptance. The need for a uniform and agreed terminology was obvious to facilitate co-operation and QM. The importance of nurses and physicians using the same terminology for documentation, was paramount.
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| 2. |
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| 3. |
- Enskär, Karin
(författare)
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Assessing the life situation of children and adolescents with cancer and their families
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In recent decades, more children have been cured of cancer due to research development and intensification of treatment. Having a life-threatening disease, like cancer, during childhood effects both the child and the family. It is important for the staff working with those families to know what is distressing in order to provide appropriate care. The aim of this thesis was to develop instruments to assess the life situation of children with cancer and their families. First, the health care personnel's (n=24) perception of problems and symptoms caused by the disease were identified. An inquiry of Delphi-technique type was used. The results gave two Lists of Problems (LoP), one with 84 problems concerning the child, and one with 69 problems concerning the rest of the family. In the next study, using qualitative interviews, children's (n~5), adolescents' (n~10) and parents' (n~16) own experience of problems related to the disease and its perceived effect on their life situation were investigated. The result from those studies formed the basis for the three scales developed in the study, the Life Situation Scales for Children 7-12 years old (LSS-C), for Adolescents 13-19 years old (the LSS-A) and for Parents (the LSS-P). A new group of children (n~15), adolescents (n~21) with cancer and their parents (n~llO) answered one of the three questionnaires. The psychometric tests of the first version of the life situation scales gave some evidence of validity and reliability. However the scales for children and adolescents, in particular, need to be tested on larger samples. The study indicated how to proceed with futher development, as the methods used seemed to be adequate. After further development the tools could be used in research and clinical care evaluations.
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| 4. |
- Ferrándiz, Rafael, 1953-
(författare)
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Allergenic characterization of the domestic mite Dermatophagoides siboney
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Allergic reactions to Pyroglyphid mites of the genus Dennatophagoides play an important role in the pathogenesis of asthma and other atopic diseases. Dermatophagoides siboney was described in Cuba in 1982. D. pteronyssinus and D. siboney are the most frequent mites in house dust collected from the homes of Cuban asthmatics, i.e., 100 and 85%, respectively.The aims of the present studies were to investigate the prevalence of sensitization to D. siboney, Blomia tropicalis and other mite species in asthmatic patients from Cuba; to study the allergenic composition and to characterize the major allergens of D. siboney extracts; to investigate the crossreactivity between D. siboney and other mite allergens, and the relevance of patient selection for the determination of the biological activity of D. siboney and other domestic mites in the tropics.Dermatophagoides siboney was found to be an important sensitizing agent among asthmatics in Cuba. Sensitization to B. tropicalis, D. pteronyssinus, D. farinae and A. siro, was also common as studied by skin and specific IgE tests. A combination of SPT with D. siboney, D. pteronyssinus and B. tropicalis diagnosed sensitization to mites in almost all mite sensitive patients. Thirteen allergenic proteins were identified in D. siboney extracts. Three components, 25, 14 and 30 kD, which bound to specific IgE strongly and frequently, were purified by affinity chromatography using crossreacting monoclonal antibodies to group 1; 2 and 3 allergens and named Der s 1, Der s 2 and Der s 3, respectively. TheN-terminal sequences of these allergens showed higher homology with D. jarinae and D. microceras than with D. pteronyssinus. The homology between group 2 allergens was higher than that of group 1 and 3 allergens.A higher degree of crossreactivity was observed between allergens from D. siboney and D. farinae than betWeen D. siboney and D. pteronyssinus, B. tropicalis, A. siro, L. destructor or T. putrescentiae. Due to the crossreactivity, Cubans not exposed to D. farinae and Swedes not exposed to D. siboney and B. tropicalis, reacted to these mites. The individual allergens of D. siboney crossreacted more with those of D. farinae and D. microceras than with those of D. pteronyssinus. The 65, 62, 37 and 30 kD proteins, always inhibited by more than 50 % by the other mite species, were the main cause of the crossreactivity, The 80 kD protein was the less crossreactive allergen. Three MoAbs directed to Der s 1, one group crossreacting and two species specific, were produced. The crossreacting monoclonal antibody partly inhibited IgE binding to Der s 1 allergen. The results confmned the existence of crossreacting epitopes onDer s 1 but also indicate that this allergen has at least one species specific epitope.The degree of reactivity to different mites seemed to be more related to patient selection criteria and extract potency rather than to exposure to a specific species.Since D. siboney is common in dust from Cuban homes, it is probably present in other Caribbean countries and found to be an important sensitizer, it has been considered a potential candidate for the development of extracts for diagnosis and therapy of mite allergy. These studies contribute to the understanding of the characteristics of the allergens from this species and their relation to other mite allergens.
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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
- Gustavsson, Johanna, 1956-
(författare)
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Insulin control of glucose transport in caveolae microdomains of the plasma membrane
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Caveolae are invaginated, dynamic microdomains in the plasma membrane and believed to be involved in receptor-mediated uptake of small molecules (potocytosis) and in signal transduction. A phosphatidylinositol glycan, a precursor of potential insulin second messengers, has been found to be enriched in the caveolae-fraction of adipocyte plasma membranes (Parpal et al., 1995, J Cell Biol 131:125-135). We now demonstrate that the insulin receptor is localized to caveolae microdomains. This was investigated in i) 3T3-Ll adipocyte plasma membranes by a morphological method (double immunofluorescence labeling and contbcal microscopy) and in ii) caveolae isolated by a biochemical, detergent-free method. The insulin receptor was enriched in caveolae and, in response to insulin, phosphorylated on tyrosine which indicated that the insulin receptor was active.Insulin stimulates the translocation of glUcose transporter protcins from intracellular stores to the plasma membrane which leads to an increased glucose uptake. Long-chain 1 ,2-diacylgiycerol, one of two potential second messengers for insulin, has been found to stimulate glucose uptake in rat adipocytes (Stn\1fors, 1988, Nature, 335:554-556). Here, we report that long-chain 1,2-diacylglycerol, emulsified in taurodeoxycholate, stimulates the translocation of GLUT4 to the plasma membrane. Moreover, physiological long-chain 1,2~diacylglycerols are taken up by different cell types in amounts sufficient to have biological eftects, equally well in the absence or presence of taurodeoxycholate.We also report that a rapid translocation of GLUT4 to the plasma membrane was followed by a slower transition of GLUT4 into caveolae. Accumulation of GLUT4 in caveolae coincided with the insulin-stimulated increase in glucose uptake. This offers a mechanistic explanation for the observed discrepancy between the appearance of GLUT4 in the plasma membrane and the delayed increase in glucose uptake.Non-hydrolyzable GTP-analogs stimulate the translocation of GLUT4 and increase glucose uptake in permeabilized cells. The small GTP·binding protein RaM is suggested to be involved in these processes since Rab4 has been localized to GLUT4-containing vesicles and is redistributed in response to insulin. We found that Rab4 is enriched in caveolae and that the amount of Rab4 increased in caveolae, in the same extent a<> GLUT4 did, in re!.J)Onse to insulin.Caveolae are characterized by high levels of sphingolipids and cholesterol. Depletion of cholesterol, which disrupts the integrity of caveolae, abolished insulin-stimulated glucose uptake reversibly. Insulin's control of protein pho.<:phorylation was also abolished while j3-adrenergic signaling was unaffected.The results suggest that caveolae are crucial Jor insulin-signuling in adipocytes and a disruption of these structures may have consequences for the development of insulin re.~istance and diabetes mellitus.
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| 9. |
- Haglund, Lena, 1953-
(författare)
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Occupational therapy assessment in general psychiatric care
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to develop an Instrument to Investigate psychiatric patients' occupational performance In order to identify their need of occupational therapy service. A literature review and analysis of different concepts used to describe the patient's activity resulted In the construction of new concepts which subdivide the activity Into elementary parts; operations, single actions, generated actions, action sequences and simultaneous actions.Occupational therapists (n = 38) In general psychiatric care collaborated In a study of the agreement level when deciding whether patients (n = 10) should be Included In, or excluded from, occupational therapy service. The results Indicate the imJ?Orlance of studying In more detail the screening process and the development of screening mstruments.One instrument, the Occupational Case Analysis Interview and Rating Scale (OCAIRS), was identified. The instrument, which gives Information about patients' adar.tive occupational functioning, was translated Into Swedish and tested for interrater reliability In two different studies. The result showed that the second version of the instrument had good lnterrater agreement.In order to investigate whether a patient's adaptive occupational functioning is related to diagnoses of schizophrenia or mood disorders, a study was made on three groups of inpatients: patients with schizophrenia (n = 18), major depression (n = 20) and bipolar disorders (n = 22). To examine the patient's occupational functioning OCAIRS was used. The result Indicated that the patient's adaptive occupational functioning was related to psychiatric diagnoses. Patients with schizophrenia and with bipolar disorders had great difficulties In adapting to everyday occupation and were In need of intervention from the occupational therapist. Patients with maJor depression, however, do not seem to have the same need of intervention.By Interviewing 145 patients, the predictive values of OCAIRS was calculated. OCAIRS seems to predict Inclusion and exclusion Into occupational therapy, seems to select which patients are In immediate need of treatment, and seems to identify those who need a new assessment later on. However, the results Indicate a need to Investigate how the rating of the different components In OCAIRS influence the occupational therapist when judging the patient's need of occupational therapy.
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| 10. |
- Hellberg, Carina
(författare)
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β2 integrin-induced signal transduction in granulocytic cells
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neutrophil granulocytcs are highly mobile, phagocytic white blood cells whose motile functions are critically dependent on adhesion receptors belonging to the B2 integrin subfamily. These integrins are vital for neutrophil functions due to their ability to generate intracellular signals. The B2 integrin~rnediated phagocytosis of complement-opsonised particles is believed to be regulated by PKC. Particle engulfment has previously been found to be accompanied by accumulation of DG, a lipid known to activate PKC. In the present experiments, this DO originated mainly from PLD-mediated hydrolysis of phosphatidylcholinc. The subsequent activation of PKC was demonstrated by the ability of this kinase to phosphorylate the PKC~ specific substrate MARCKS. Moreover, PKC regulated the activity ofPLD in a positive way and thereby maintained its own activity. PKC has also been shown to phosphorylate the B2 subunit of the integrin. Although this phosphorylation does not regulate the avidity of the integrins, it may be needed for the induction of intracellular signals. However, antibody-induced ligation of B2 integrins did not alter the phosphorylation status of these integrins, indicating that this phosphorylation is not involved in the generation of second messengers. In contrast, pretreatment of cells with phorbol esters inhibited the tyrosine kinase activation and the subsequent rise in cytosolic free Ca2+ in a way that correlated with its ability to induce a phosphorylation of the B2 subunit of the integrin. Therefore, a PKC-mediated phosphorylation of this subunit may represent a mechanism for other receptors to regulate the signalling capacity of B2 integrins.The B2 integrin-induced ca2+ signal was shown to be due to both a release of ca2+ from intracellular stores and an influx across the plasma membrane, Moreover, integrin ligation induced a tyrosine phosphoryialion of PLCy2 accompanied by a small formation of Ins(1,4,5)P3, indicating that PLCy2 is responsible for the intracellular release of ca2+. Further evidence was provided by the findings that an activation tyrosine kinase(s) precedes, and is a prerequisite for, the rise in cytosolic free ca2+ concentration. The Src family tyrosine kinase Fgr is activated by B2 integrin-dependent neutrophil adhesion, and this occurs through mechanisms that are yet unidentified. The present results show that ligation of B2 integrins elicited a rapid and transient association of Fgr with B2 integrins. The tyrosine kinase inhibitor genistein did not affect this association, but it did prevent the subsequent dissociation. The interaction between these two proteins could represent an initial step in the B2 integrin-induced activation of Fgr, whereas the dissociation of Fgr from B2 integrins appears to be dependent on the activation of a tyrosinekinase, probably Fgr itself.
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