<p>Physicians are supposed to act as sick-listing experts and they possess a role as gate-keepers to the social insurance system. Earlier studies have demonstrated variation between physicians and physician categories regarding sick-listing practice. In addition to the patient's disease and its severity, a number of other factors may be expected to influence sick-listing practice. Most earlier studies have focused on the patient's disease and his or her work place as cause for sickness absence.</p><p>The aims of this study were to analyse variation of sick-listing practice between physician categories and the influence of physician characteristics on sick-listing practice, the influence of structure, organisation and remuneration of health care on physician sick-listing practice, the influence of local structural factors in the community, and the influence of a legislative change on physician sick-listing practice.</p><p>The study was conducted as a cross-sectional epidemiological study of 57563 doctors’ certificates for sickness absence, received by 28 local social insurance offices in eight Swedish counties, during four months in 1995 and two months in 1996.</p><p>Patient age, sex, and diagnostic group, issuing physician category, presence of a hospital in the municipality, municipality population size and county were all significantly and independently correlated to number of net days of sick-listing. Physician characteristics, such as age, sex and degree of specialisation were all associated with number of net days of sick-listing. Physicians working in general practice issued significantly shorter periods of sick-listing than the other physician categories. Reimbursement of general practice and participation in financial co-operation with social insurance were significantly correlated to length of sickness episode issued by general practitioners. A legislative change performed during the study period was associated with small effects in sick-listing practice.</p><p>In conclusion, a number of factors other than disease and disease severity and other patient and physician linked factors were found to influence the variation of sick-listing practice. It appears that the closer the influencing factor was to the place were the decision was taken, i.e., the patient-physician consultation, the higher the impact on the decision appeared to be.</p>

<p>The present work is analyzing the general biomechanical aspects of fixation techniques in the upper and lower cervical spine along with clinical implications.</p><p>The in vitro biomechanical properties of five different posterior atlanto-axial fixation techniques are compared. They provided for either a one, two or three-point fixation between atlas and axes. A new device, the C1 claw was biomechanically tested, which allow for fixation without the need for a structural bone graft. The three-point reconstructions indicated superior biomechanical properties compared to all others.</p><p>The new C1 claw device was clinically evaluated in a series of 26 patients treated with a posterior C1-C2 fusion. There were no clinical or radiological failures in the series, Twenty-one patients out of twenty-three with any length of follow up either showed a solidly healed fusion or a healed fracture. </p><p>Distractive flexion (DF) injuries in the lower cervical spine treated with anterior plate alone were analyzed with respect to healing rate and complications in a consecutive series of 36 patients. Results indicated that DF injury stage 1 and 2 according to Allen and Ferguson healed without complication, whereas DF injuries stage 3 had a high frequency of failure, needing an additional posterior fixation. </p><p>The in vitro biomechanical properties of four different fixation techniques for a distractive flexion injury stage 3 were analyzed. The result indicated that anterior plate alone for fixation of a DF injury stage 3 is insufficient supporting the clinical finding in the previous study.</p><p>Adjacent level motion was analyzed following a one segment fusion in the lower cervical spine. Motion was found to increase in adjacent levels possibly contributing to accelerated degeneration.</p>

<p>The blood vessels of the pancreatic islets are of crucial importance for oxygen and metabolite supply as well as dispersal of secreted hormones. In addition to this, endothelial cells have an important role in the revascularization process after islet transplantation. Previous studies have reported signs of poor engraftment of transplanted islets, presumably due to impaired revascularization. The aims of this thesis were to investigate the revascularization process of transplanted islets and to examine the role of islet endothelial cells. In this context, the lectin Bandeiraea simplicifolia was found to stain endothelium of both endogenous and transplanted pancreatic islets. By using this lectin we investigated the vascular density of both endogenous and islets transplanted syngeneically beneath the renal capsule, into the spleen or intraportally into the liver of normoglycemic C57BL/6 mice. One month post-transplantation, a time point when the grafts are assumed to be completely revascularized, the vascular density was decreased at all three implantation sites when compared to endogenous islets. Furthermore, most of the blood vessels were located in the graft connective tissue stroma. Similar results were obtained when islet transplant vascular density was determined six months post-transplantation and in cured diabetic animals after one month. In order to evaluate the function of intraportally transplanted islets, we developed a method to retrieve such islets. We treated the implantation organ (liver) first enzymatically (collagenase) and then mechanically, thereafter we could re-isolate the transplanted islets for further in vitro studies. The retrieved islets had a decreased insulin relase, insulin content and glucose oxidation rate when compared to non-transplanted control islets. To understand the role of islet endothelium in the revascularization of transplanted islets we performed angiogenesis GEArray studies on islet endothelial cells, from non-cultured, cultured and transplanted islets. We found that the islet endothelium expressed mRNA for both inhibitors and inducers of angiogenesis, and that this expression differed with time. The functional consequences of this remain to be determined. In summary, the results presented above provide a useful platform for future studies of the morphology and function of islet endothelial cells, especially with a view for elucidating changes induced by islet transplantation.</p>

<p>Cardiopulmonary bypass (CPB) is associated with inflammatory response and activation of coagulation. Heparin coating of the CPB circuit is shown to improve the biocompatibility of the surface. The biological effects of a new heparin surface, the Corline Heparin Surface (CHS), prepared according to a new principle, have been studied. </p><p>The CHS used during coronary artery bypass grafting with CPB in sixty patients prevented adhesion of cells to the extracorporeal device. The activation of inflammation, coagulation, and fibrinolysis was significantly reduced by the use of CHS. Both a reduced and an increased dose of systemic heparin in combination with the heparin-coated surface resulted in more activation of inflammation and coagulation. </p><p>Photoelectron spectroscopy studies of the molecular structure of the CHS demonstrated that a single layer of the heparin surface, equivalent to what was used in the <i>in vivo</i> studies, did not completely cover the substrate surface. Additional layer of immobilized heparin has resulted in a complete coverage. We examined the biological effects, i.e. activation of inflammation and coagulation, by CHS in one and two layers in an <i>in vitro</i>-study. The data from this study clearly demonstrated that a uniform surface coating of the CHS results in only minor activation of coagulation, inflammation and cell activation. </p><p>Monocytes do not normally express tissue factor (TF), initiator of the coagulation <i>in vivo</i>, but can be induced upon adhesion to artificial surfaces. TF is receptor for coagulation factor VIIa (FVIIa) and binding subsequently leads to formation of thrombin. Other biological effects beyond coagulation, as inflammation and angiogenesis, has recently been associated with the formation of TF·FVIIa. The TF∙FVIIa signal transduction induced an increased sensitivity to PDGF-BB-stimulated migration and an increased production of IL-8 and TNF-α in monocytes. These could be important mechanisms for continued recruitment of cells to sites of inflammation. </p>

<p>The purpose of gene mapping is to understand the underlying genetics of simple and complex traits like plumage colour and growth. This thesis is based on a cross between the wild ancestor of the modern chicken, the red junglefowl, and a White Leghorn line selected for high egg mass. There are obvious phenotypic differences between these two breeds in several aspects such as growth, egg production and behaviour. These complex traits are often influenced by a number of genes or Quantitative Trait Loci (QTL) as well as environmental factors.</p><p>Identification of QTL regions involves testing of association between genetic markers and the phenotype of interest. The QTL identified in this study explain most of the difference in adult body weight between the red junglefowl and the White Leghorn, but less of the difference at earlier age. By applying a different method for detection of QTL, including gene interactions, epistasis, we can understand more of the genetics behind early growth. The allele coming from the red junglefowl is generally associated with lower weight, egg production and food consumption.</p><p>In this study we have also identified two genes explaining the difference in plumage colour in the cross. The <i>Extension</i> locus, encoded by the melanocortin receptor 1 (<i>MC1R</i>), controls the amount of pigment produced has shown to be associated with plumage colour. A mutation in the <i>MC1R</i> gene causes black pigmentation of the plumage. </p><p>We have also found association between the <i>PMEL17</i> gene, known to be involved in normal pigmentation, and the <i>Dominant white</i> phenotype present in the White Leghorn. After comparison of sequences from different alleles at the <i>Dominant white</i> locus, amino acid alteration caused by insertion and deletion in the transmembrane region of the <i>PMEL17</i> protein has been revealed. These mutations are associated with alleles representing different plumage colour variants.</p>

<p>In the field of transplantation, the increasing deficit of human donors have lead to an interest in animals as an alternative source of organs and tissues. </p><p>Different <i>in vitro </i>systems and rodent models of xenotransplantation were used to examine the most significant barriers that have to be overcome, before isolated islets of Langerhans from pigs can be used as a cure for insulin-dependent diabetes mellitus in humans.</p><p>In clinical transplantation, islets are infused into the liver through the portal vein. During this procedure the islets are susceptible to harmful innate reactions triggered in blood. Adenoviral vectors generating transgenic expression of human complement regulatory proteins were evaluated in pig islets and shown to confer protection against acute complement-mediated damage. </p><p>Transplanted islets escaping this immediate destruction will be targets of a cellular immune response. Using a new mouse model of islet xenograft rejection, it was demonstrated that macrophages, effector cells in the rejection, were part of an MHC-restricted xenospecific immune response mediated by T cells. In a strain of knockout mice it was further shown that this process can proceed in the absence of an important signalling system, mediated by Toll-like receptors, between cells in innate and adaptive immunity. These findings illustrate some of the mechanistic differences compared to cellular islet allograft rejection which partly explain why immunosuppressive drugs used in clinical allotransplantation is not sufficient for preventing xenograft rejection. </p><p>Porcine endogenous retroviruses (PERV) remain a safety concern in xenotransplantation. Characterization of PERV in pig islets indicated that virus expression is low <i>in vitro </i>but increases during the immediate time period following transplantation. This suggests that antiviral therapies administered at the time of transplantation could be used for preventing the risk of PERV transmission after xenotransplantation.</p>

<p>The overall aim of this thesis was to gain a deeper understanding about parents’ perceptions of quality of care and their own involvement in pediatric hospital care.</p><p>Parental involvement in the care of hospitalized children has gained increased attention in recent years. The aim of this thesis was to study parental involvement in pediatric hospital care and investigate its association to the work conditions of pediatric hospital staff. </p><p>The first study validated a parent questionnaire that measured parents’ views of the quality of care. The questionnaire measures quality of care by means of eight indices and an overall quality grade. Results showed that the questionnaire demonstrated satisfactory validity and reliability. </p><p>Study 2 examined whether there were differences in quality ratings between respondents and non-respondents to the parent questionnaire. The main parent questionnaire was distributed in hospital and a follow-up questionnaire was sent home to a random sample of parents three week after the hospital visit. This study pinpointed a number of difficulties that need to be considered when conducting investigations of non-response.</p><p>The third study aimed at gaining a deeper understanding of factors that influence parents’ views of their own involvement in pediatric care. Semi-structured interviews were conducted with parents of chronically ill children. Four themes emerged from the interviews: support, professionalism, work environment and responsibility. Underlying these four themes is a need for a clear communication between staff and parents.</p><p>The fourth study examined hospital staff’s perceptions of parental involvement and possible consequences for staff work environment. A questionnaire was sent out to hospital staff at oncology, neurology and surgery units at three university children’s hospitals. Hospital staff on oncology units gave higher ratings to their workplace routines for involving parents in the child’s care, and experienced less work strain from parental demands, compared to staff on the other units. </p><p>The results of this thesis indicate a clear association between parental involvement in pediatric care and the work conditions of pediatric hospital staff. </p>

<p>During the past decades the knowledge concerning risk factors and pathophysiology of coronary heart disease (CHD) has substantially increased. However, despite identification of important risk factors CHD remains the leading cause of death in the western world.</p><p>The metabolic syndrome is a cluster of metabolic disorders such as hypertension, hypertriglyceridemia, low HDL-cholesterol, and glucose intolerance associated with an increased risk of cardiovascular morbidity and mortality.</p><p>The studies in this thesis are epidemiological in their character, and examine the relationships between different aspects of CHD and the metabolic syndrome in a population-based study of middle-aged men (ULSAM).</p><p>The findings indicated that serum lipids were important risk factors for the development of both angina pectoris demanding revascularisation and acute myocardial infarction (MI). Proinsulin and blood pressure were independent predictors of MI only, suggesting these factors to be involved in thrombosis and plaque rupture. </p><p>It was also found that antihypertensive treatment with beta-blockers and thiazide diuretics resulted in increased fasting blood glucose concentrations in subjects with an insulin resistant state with elevated proinsulin concentrations. Both proinsulin concentrations and increase in fasting blood glucose were associated with increased risk of developing future MI. </p><p>The finding of a new Q/QS-pattern on the resting ECG, regardless of history of MI, was associated with impaired insulin secretion and was an independent predictor of total and cardiovascular mortality. </p><p>A risk prediction score for MI including proinsulin and the ratio between apolipoprotein B and apolipoprotein A1 was developed in middle-aged men. This score was predictive for future fatal and nonfatal MI, and proved to be at least as good as the Framingham and the PROCAM scores, being based on traditional risk factors.</p><p>In summary these studies provide further knowledge about the associations between CHD and the metabolic syndrome and the possible importance of new markers of cardiovascular risk such as proinsulin and the apolipoproteins.</p>

<p>Positron Emission Tomography (PET) permits regional myocardial perfusion, fibrosis and oxidative metabolism to be non-invasively quantified with radioactive tracers such as [¹⁵O]-water and [1-¹¹C]-acetate. PET is an established research tool in congestive heart failure (CHF), a major cause of morbidity and mortality. However, as CHF is a syndrome that eventually affects all aspects of cardiac and systemic hemodynamic function, more clinically relevant information from a single PET scan is desirable. The aim of this thesis therefore was to develop and implement some new concepts in cardiac PET.</p><p>A new method for the measurement of cardiac output with any tracer was validated in animal experiments and CHF patients. The early pulmonary retention of [1-¹¹C]-acetate was inversely related to left ventricular (LV) function in animals and was directly proportional to lung water content and severity of LV diastolic dysfunction in patients.</p><p>Eight patients with acute myocardial infarction were followed with serial PET from 3 hours to 3 weeks after trombolytic treatment. PET revealed that myocardial perfusion and the extraction and utilization of fuel substrates all decreased closer to the infarct centre. The rate of oxygen utilization within the infarct at 3 h predicted degree of myocardial fibrosis, pulmonary oedema and tissue viability at 3 weeks. </p><p>Seventeen patients with CHF due to chronic ischemic cardiomyopathy and severely reduced LV function were evaluated with [1-¹¹C]-acetate PET before and after coronary artery bypass surgery. There was a dramatic improvement in physical performance and symptoms, which was not correlated to the standard LV ejection indices. PET revealed that functional improvement was associated with improved LV loading conditions, reversed remodeling and homogenization of oxidative metabolism rather than increased output.</p>

<p>Reverse transcriptase (RT) is a crucial enzyme for retrovirus replication, and its presence in the virion is indispensable for infectivity. This thesis illustrates the use of RT activity assays as tools for quantitation and characterization of different retroviruses, particularly HIV. </p><p>A non radioactive assay, using microtiter plates, for the RT of Moloney murine leukemia virus (MMuLV) was developed. Assay conditions for MMuLV and HIV-1 RT, together with isozyme specific RT activity blocking antibodies, were shown useful for discrimination between RTs from different retrovirus genera. RT activity assay for HIV-1 was found to quantitate different subtypes more equally efficient than p24 antigen assays did.</p><p>Viral load (VL), the amount of HIV particles in the blood, is an important marker of the clinical status of an infected person. A method for VL determination based on RT activity (ExaVir Load) was developed. After plasma pretreatment, to inactivate cellular DNA polymerases, virions in patient plasma were immobilized on a gel, which was washed to remove disturbing factors. The virions were lysed with a detergent containing buffer and the lysate eluted. Finally, the RT activity in the lysate was determined and found to correlate strongly to VL by RNA according to a PCR based standard method (Roche Amplicor 1.5). The second version of the method was able to measure VL down to approximately 400 HIV-1 RNA copies/ml. The usefulness of RT from the VL procedure for determination of susceptibility towards anti-HIV drugs was demonstrated, and the results were in agreement with genotypic data. </p><p>Due to its technical simplicity, and ability to detect a broad range of HIV-1 subtypes, ExaVir Load and the drug susceptibility application are interesting for clinical use, particularly but not only in resource limited settings. The concept is also potentially useful for research purposes, e.g. in combination with specific RT assay conditions.</p>