| 1. |
- Borssén, Bengt, 1946-
(författare)
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Foot lesions in diabetic patients aged 15-20 years : a population-based study
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Foot problems are not only the most common but in general also the most severe of the diabetic complications. The age group 15-50 yrs in this study was chosen because these patients were considered to be at their most active age and were felt to require optimal foot function.380 patients (96 %) participated, 78 % with Type 1, 20 % Type 2 and 1 % with secondary diabetes mellitus (DM) and 100 healthy controls. Only six patients had signs of peripheral ischaemia but half of the patients had deformities such as fallen forefoot arches and hammer toes. With sensory thresholds and clinical signs it was demonstrated that age, duration of DM and tall stature are major risk factors for diabetic neuropathy. Gender differences depend on differences in height. Dorsiflexion of the toes against resistance was used to test the function and volume of m.extensor digitorum brevis. When compared with measurements of sensory thresholds for vibration, perception and pain, it was found to be a valuable test for screening of distal motor neuropathy.To prevent worsening of foot deformities 266 patients with Type 1 DM were followed for 3 years. Those with the most pronounced deformities were fitted with custom-made insoles and had repeated examinations. Improvement was more common in patients with insoles compared to patients without insoles.Bone mineral density (BMD) was measured in nine patients with osteopathy in their feet and 18 controls. BMD was lower in L2-L3, but not in the proximal femur, implying osteopenia being a possible risk factor for distal osteopathy.Plaster cast treatment was used in 33 diabetic patients with severe foot ulcers who were selected because previous conservative treatment had been unsuccessful and they had been judged unsuitable for vascular surgery. The lesions healed in 19 patients.In conclusion, the main findings demonstrate the need for an increased awareness of early preventive foot care in young and middle-aged diabetic patients.
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| 2. |
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| 3. |
- Hedén, Bo
(författare)
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Analysis of Electrocardiograms Using Artificial Neural Networks.
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Most conventional ECG interpretation programs use decision tree logic for interpretation of the ECG. The performance is generally good but can be improved. Artificial neural networks represent a new computer method, which has proved to be of value in pattern recognition and classification tasks. The purpose of the studies in this thesis was to improve the analysis/interpretation of the 12-lead ECG by using artificial neural networks. The input values to the networks are extracted from the measurement section of a commercially available interpretation program. No special recording technique or devices have to be used. The results show that artificial neural networks improve computerized ECG interpretation for the diagnosis of acute and healed myocardial infarction. They also perform well in quality control of the ECG recordings by detecting lead reversals with high sensitivity and specificity. The output values from an accurately trained neural network can, under certain conditions, be regarded as a posteriori probabilities for a diagnosis. The output values can also be transformed to verbal statements concerning different probability levels for healed myocardial infarction. The agreement between these probability estimates and those of an experienced electrocardiographer was high. The results indicate that artificial neural networks, if properly trained and validated, will be a useful aid in the attempt to improve the diagnostic yield of the 12-lead ECG.
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| 4. |
- Yeung, Moorix Mo-Wai
(författare)
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Specific and nonspecific immune mechanisms in human gut : a comparative study of normal and ulcerative colitis intestine
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The intestine, with its large mucosal surface area, digests and absorbs food nutrients and maintains a beneficial microbial flora in the colon. Local protective immune responses against intestinal pathogens ensure the survival of the individual. These immune reactions are both specific and non-specific in nature. The intestinal epithelium is single-layered and constantly renewed with differentiating epithelial cells moving from the crypt to the luminal surface. Intraepithelial lymphocytes (IEL) are interspersed between the epithelial cells. Ulcerative colitis (UC) is a life-threatening chronic inflammation affecting colon.In this study three molecules belonging to the carcinoembryonic antigen (CEA) family, namely CEA proper, nonspecific cross-reacting antigen 50/90 (NCA 50/90) and biliary glycoprotein (BGP), were found to be specifically localized to the apical surface of colonic epithelial cells. Full expression of these molecules occurs when the cells reach the upper 1/3 of the crypts and are maintained on the mature cells at the luminal surface. Ultrastructurally, CEA, NCA50/90 and BGP are localized to microvesicles and microfilaments of the fuzzy coat/glycocalyx as well as to the microvilli of the epithelial cells. Their unique localization and documented bacterial binding capacities suggest that they have a role in innate immunity.Functional analysis of IEL in normal jejunum, ileum and colon revealed that IEL are in vivo activated T-lymphocytes expressing mRNA for the cytokines IL-1β, IL-2, IL-8, IFNγ and TNFα and that jejunal IEL have T-cell receptor (TCR)/CD3 dependent cytolytic capacity. As many as 10% of IEL actively produce IFNγ. CD4+TCRαβ+IEL, CD8+TCRαβ+IEL and CD4-CD8-TCRαβ+IEL all had a TH1/cytotoxic cytokine profile. IEL could be further stimulated in vitro to express IL-10, TNFβ and TGFβ1, to proliferate and to secrete IFNγ. Thus, active protection and/or regulation of the epithelium via cell-mediated immune reactions are prominent in the gut.UC colon was characterized by a marked lymphocyte infiltration in the lamina propria, 10-50 times the normal level. Most lymphocytes were present in follicle-like cell aggregates containing both T- and B-cells. An unexpected finding was that γδT-cells constituted about 15% of the cells in the aggregates. Such cells are only found intraepithelially in normal gut. γδT-cells of both the intestinal- (TCR-Vδ1/Vγ8) and blood type (TCR-Vδ2/Vγ9) were seen. T-cells in UC colon were activated but nonproliferating and had a down-regulated TCR/CD3 complex. RT-PCR and quantitative immunohistochemistry for cytokine mRNA (n=11) and protein respectively, revealed that the T-cells in UC colon did not produce IL-2, in marked contrast to T-cells in normal colon and to ileal T-cells from UC patients. This was a selective defect since TNFα, IFNγ, IL-1β, IL-8 and TGFβ1 were similarly expressed in normal colon. No TH2 cytokines were seen. Lamina propria leukocytes in UC colon expressed IL-6, a cytokine not found in normal colon. The epithelial cells of UC colon were activated expressing MHC class II antigens, heat shock proteins and the co-stimulatory molecule B7.1/CD80.Our study demonstrates that UC is an immunological disease. The immunopathological picture seen in UC colon probably reflects an inappropriate down-regulation of local immune responses perhaps due to a selective loss of the key cytokine IL-2 in a situation of extreme antigenic stress.
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| 5. |
- Janciauskiene, Sabina
(författare)
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Hydrophobic interactions of serpins
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The proteins of the serpin family are primarily but not exclusively proteinase inhibitors, which share a common, similar structure. It is known that this structure undergoes major conformational changes upon cleavage in the serpin reactive site loop, and that these changes include rearrangements within the hydrophobic core of the molecule. AAT and the free C-terminal peptide dissociated from cleaved AAT are found in human bile, where they are exposed to high concentrations of hydrophobic compounds, such as cholesterol and denaturing bile salts. ACT has been identified in the amyloid deposits of Alzheimer`s disease, where it is exposed to the hydrophobic peptide, Ab, from which neurotoxic amyloid fibrils are formed. The present studies were designed to determine the effects of such hydrophobic components on AAT and ACT. The interactions of AAT with hydrophobic bile acids and with its own hydrophobic C-terminal peptide were studied. The effects of these small molecules on the structure and biochemical properties of AAT were determined. The interaction of ACT with Ab was characterized, and the effects of ACT on fibril formation were determined. The binding of small sterol ligands in the hydrophobic core of AAT alters the conformation and aggregation properties of AAT. Large scale changes of AAT structure also occur in bile, which result in alteration of antigenicity and loss of activity of AAT. The C-terminal peptide from AAT has been found to polymerize into amyloid fibrils, which can be disrupted by intact AAT. The heterogeneous fibrils formed from the immunoglobulin lambda light chain were also found to be disaggregated by intact AAT. A specific interaction of ACT with Ab was found to be dependent on the concentrations of both interacting components and to affect the fibrillogenic property of the peptide and the heat stability and inhibitory activity of ACT. Available structural information and solution stability data enabled a model of the complex between ACT and Ab to be designed and a mechanism proposed of the action of ACT in fibril formation. Interaction of AAT and ACT with specific hydrophobic molecules and milieus results in conformational transitions of the serpin structure, with attendant changes in physicochemical properties which may be relevant to disease states.
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| 6. |
- Wållberg Jonsson, Solveig, 1953-
(författare)
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On inflammation and cardiovascular disease in patients with rheumatoid arthritis
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients with rheumatoid arthritis (RA) have a shorter life span than the general population. An increased death due to cardiovascular disease (CVD) has been reported. RA is characterized by synovitis and joint destruction accompanied by an acute phase reaction and systemic features. The present work investigates the epidemiology of CVD in patients with RA in the county of Västerbotten and the influence of inflammation on lipid metabolism and haemostasis.In a retrospective cohort study on 606 RA patients, the overall mortality was significantly higher than in the general population, with an excess death rate for CVD and for ishemic heart diseae (IHD) in both sexes. Multiple Cox regression, showed that male sex, higher age at disease onset and cardiovascular event increased the risk for death. Male sex, high age at disease onset and hypertension increased the risk for cardiovascular event. Diabetes mellitus, treatment with corticosteroids, disease modifying antirheumatic drugs and postmenopausal estrogen neither influenced survival nor the risk of cardiovascular event.In 93 patients with active RA, the levels of cholesterol, high density- (HDL) and low density (LDL) lipoprotein cholesterol were significantly lower, and Lipoprotein(a) was significantly higher compared to controls. In a follow-up on 53 patients, a relation between the change of Lp(a) and acute phase proteins was found only in patients with high levels of Lp(a). Preheparin lipoprotein lipase (LPL) activity and mass were significantly decreased in 17 postmenopausal women with active RA. Preheparin LPL mass correlated inversely to several acute phase proteins and interleukin-6. Low levels of LPL mass may implicate increased hepatic clearence but also increased macrophage ingestion of lipoproteins via the LDL receptor-related protein (LRP).Haemostasis of the circulation was investigated in 74 of the 93 patients with active RA. In patients with extraarticular disease, the release of tissue plasminogen activator (tPA) was significantly decreased, and its inhibitor (PAI-1) was significantly increased compared to patients with nonsystemic disease, implicating hypofibrinolysis. In a two year follow-up, patients with thromboembolic events had significantly elevated levels of von Willebrand factor, PAI-1, triglycerides and haptoglobin compared to event-free patients.In 29 RA patients and 18 spondylarthropathy patients with gonarthritis, radiological joint destruction correlated to PAI-1 antigen in synovial fluid and, inversely, to plasminogen. A relationship between activation of fibrin degrading proteolytic enzymes and joint destruction was implicated.In conclusion, several processes involved in lipid metabolism and haemostasis are influenced in active RA. In view of the increased death rate due to CVD, an efficient control of inflammation should be important, not only for reducing joint destruction, but also for reducing systemical atherogenic and thrombogenic effects.
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| 7. |
- Axelsson, Paul
(författare)
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On lumbar spine stabilization
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 71 consecutive posterolateral lumbar fusions without decompression or internal fixation were evaluated with a mean follow-up time of 3.5 (2-7) years. The diagnoses were spondylolysis-olisthesis in 43 cases, degenerative disc disease and/or facet joint arthrosis in 16 cases and pain post laminectomy/ decompression in 12 cases. 54/70 patients had a solid fusion. In the group with spondylolysis-olisthesis, 29 patients were good and clinical improvement correlated with solid fusion. For both the other diagnostic groups, the clinical outcome was inferior and less correlated to the radiographic result. In 50 patients scheduled for lumbar fusion, spinal immobilization in a lumbar orthosis had some pain relieving effect registered before surgery, but this pain relief could not predict the clinical outcome of subsequent surgery. External pedicular fixation provided an adequate mechanical basis for the prognostic external fixation test in lumbar fusion studied by roentgen stereophotogrammetric analysis (RSA) in 7 patients. Fusion of the olisthetic lumbosacral segment transformed mobility to the juxta-fused level inducing relative hypermobility in this segment in 2 out of 6 patients examined by RSA. The healing rate of noninstrumented posterolateral lumbar fusion was increased by extending the postoperative immobilization period from 3 to 5 months. A lumbar orthosis, soft or rigid, could not stabilize the intervertebral translations studied by RSA without active mobility provocation, consistent with the postoperative regimen when the patient cooperates to minimize gross body motions and keeps the trunk straight. Adding unilateral hip fixation to the orthosis yielded a tendency towards intervertebral stabilization however not shown important for the postoperative situation after fusion. During this period any lumbar support can be used as long as it reminds the patient of the regimen to avoid all active movements of the spine.
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| 8. |
- Eckerwall, Göran
(författare)
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Legg-Calvé-Perthes´ disease. Synovitis, cartilage, remodeling
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis evaluates and correlates the findings in a series of children with Legg-Calvé-Perthes´ Disease at the Departments of Orthopedics, University Hospitals in Lund, Sweden and Odense, Denmark during 1984-1993. It focuses on the importance of synovitis and its effect on the cartilage, on the shape of the femoral head in the early phases of LCPD and on femoral head remodeling after proximal femoral varus derotation osteotomy. Synovitis, i.e.inflammation and edema of the synovium with or without joint effusion, can be diagnosed sonographically in LCPD. Significantly increased concentrations of proteoglycan fragments and stromelysin-1 in hip joint effusions, confirms the presence of synovitis. It causes an increase in intracapsular pressure, the magnitude of which may intermittently compromise the blood supply to the proximal femoral epiphysis and metaphysis. Synovitis persists late in the course of the disease and seems to be an important factor as regards symptoms and prognosis; It causes pain and decreased range of motion and, if persistent, contracture of the joint. Moreover, synovitis may be responsible for the cartilage hypertrophy and subsequent lateral subluxation with poor containment, deformation and incongruency. Consistent signs of fat necrosis in the proximal metaphysis with reactive, reparative changes, indicates previous episodes of ischemia in a prognostically poor subset of LCPD. The bony shape seen on conventional radiography does not adequately reflect the cartilage shape of the femoral head on MRI or on arthrography. MRI provides early and reliable information about the cartilaginous outline of the head of the femur, thus constituting a potential, early prognostic tool. MRI also provides earlier and more reliable information on the remodeling of the femoral head in LCPD than conventional radiography does. In a subset of prognostically poor cases of LCPD, there is an early, continuous spherical remodeling of the femoral head following proximal femoral varus derotation intertrochanteric osteotomy.
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| 9. |
- Erjefält, Jonas
(författare)
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Airway epithelial shedding: Morphological and functional aspects in vivo.
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Epithelial damage may contribute to the pathology in airway diseases such as asthma and rhinitis. However, the distribution of epithelial shedding in inflammatory airway diseases and, particularly, the ensuing repair processes are largely unknown. In the present studies we have developed novel in vivo techniques to explore epithelial repair mechanisms and associated tissue responses occuring in guinea-pig trachea after mechanical-induced epithelial shedding or an allergic inflammation. The results emerging from the studies of mechanichal shedding and repair include: morphological characterisation of prompt dedifferentiation of both ciliated and secretory epithelial cells into repair cells that with a high speed migrate to cover the denuded basement membrane. Another major finding was that epithelial shedding, by itself, evoked several disease-like tissue responses such as plasma exudation, hypersecretion, and infiltration and activation of neutrophils and eosinophils. Repeated treatment with a potent topical glucocorticoid (budesonide) did not affect the speedy epithelial restitution and its associated tissue responses. A novel technique was developed to selectively remove columnar epithelial cells to demonstrate that also airway basal cells have a capacity to promptly assume a barrier structure. In vivo allergen challenge, selectively of the large airways, produced crater-like damage sites in the epithelium. Dedifferentiated repair cells were present at the floor and the borders of these damage sites. Activated granulocytes and extravasated plasma proteins abounded in the airways, particularly in association with the damage sites. In conclusion this thesis demonstrates that epithelial repair after mechanical or allergen-induced epithelial shedding is a speedy an efficient process with the participation of basal, secretory, and ciliated cells in a milieu of plasma exudates and leukocytes. This thesis further shows that in allergic inflammation patchy epithelial damage areas are dynamic sites where damage and repair processes occur simultaneously and where plasma exudates and activated leukocytes accumulate. If transferable to human airways the present observations on sequelae to epithelial shedding suggest that epithelial restitution processes quickly restore a barrier structure but causes also effects that significantly contribute to the pathology and pathophysiology observed in inflammatory airway diseases.
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| 10. |
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