<p>The aims of the present thesis were to survey the prevalence and incidence ofpressure ulcers in patients with hip fracture and to investigate nursing staffknowledge and documentation regarding pressure ulcer prevention for the samepatient group. Another aim was to test the effect of three preventive interventions:risk assessment and pressure ulcer grading, a pressure-reducing mattress and aneducational programme. Experimental, comparative and descriptive designs wereused and quality improvement philosophy guided the research. In 1997 and 1999, atotal of 124 and 101 patients > 65 years with hip fractures were included andfollowed with risk assessment and skin observation. Audit of patient records, aquestionnaire to nursing staff and a focus group interview were also employed.</p><p>The findings from the first studies showed that 20% of the patients hadpressure ulcers on arrival to the hospital. During the hospital stay, 55% developednew pressure ulcers. Nursing staff knowledge and documentation regardingpressure ulcer prevention was unsatisfactory. An extensive educational programmewas developed and conducted in 1998. Twenty-five registered nurses participatedfrom the hospital and the community setting.</p><p>There were no significant differences in the prevalence/incidence ofpressure ulcers between the experimental and control groups in the twoexperimental studies. However, there was a significant reduction of the incidence ofpressure ulcers between 1997 and 1999 (from 55% to 29%). The focus group indicatedthat there had been changes since 1997 in nursing and treatment routines in theAccident and Emergency Department and in the orthopaedic wards.</p>

<p>Left ventricular hypertrophy (LVH) and the insulin resistance syndrome are common conditions associated with a markedly increased cardiovascular risk. In a fairly large prospective longitudinal study of men from the general population, we found that an unfavorable serum fatty acid profile and components of the insulin resistance syndrome such as dyslipidemia, obesity and hypertension at age 50 predicted the prevalence of LVH at age 70. In cross-sectional analyses at age 70, several components of the insulin resistancesyndrome were significantly related to left ventricular relative wall thickness and concentric remodeling, but less to LVH. Left ventricular relative wall thickness was inversely related to insulin sensitivity in skeletal muscle and borderline significantly directly related to insulin sensitivity in the myocardium in a healthy, normotensive sample of the cohort investigated with positron emission tomography, whereas left ventricular mass index was not related to myocardial or skeletal muscle insulin sensitivity. At age 70, echocardiographic LVH was related to a variety of common electrocardiographic diagnoses. In a prospective mortality analysis with baseline at age 70 and a median follow-up time of five years, echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of other cardiovascular risk factors, implying that echocardiographic and electrocardiographic LVH in part carry different prognostic information.</p><p>In summary, components of the insulin resistance syndrome predicted LVH twenty years later, but were cross-sectionally more related to increased left ventricular relative wall thickness and concentric remodeling. Echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of components of the insulin resistance syndrome.</p>

<p>The sick building syndrome (SBS) comprises eye, nose, skin, and throat symptoms, headache and fatigue. Gender, personality aspects, and psychosocial factors at work have lately been at focus in health research. The main aim of this thesis was to investigate the relationships between SBS and personal factors, personality traits, and psychosocial work stress. Two different populations were studied: a cohort of 195 subjects working in suspected “sick buildings” followed 1988-1999, and a random sample of 695 subjects from the Swedish population, 20-65 y. Two personality scales were used; the Karolinska Scales of Personality (KSP) and the Sense of Coherence (SOC). Two stress questionnaires were used: the 3-dimensional demands-control-support model (DCS) and the Assessment of Perceived Psychosocial Work Environment (PPWE). SBS and personal factors were assessed by a postal symptoms questionnaire and a symptom score (SC) was calculated. Personality was assessed by means of two verbal personality scales, the KSP and the SOC. Females in problem buildings had more SBS than men, and females had a lower SOC and more anxiety and aggressivity in the KSP. Females and males in the general working population reported differences in psychosocial work environment. Moreover, the associations between personality traits and SBS, and between DCS and SBS, differed between males and females. Over all, the investigated occupants of suspected sick-buildings were within the normal range for both KSP and SOC norms. However, those with symptoms showed prominent personality vulnerability, especially in anxiety, aggressivity, and lower SOC, compared to those that were not reporting symptoms. Female gender, low age, asthma, and a history of atopy were related to SBS in the general working population. A combination of low social support and either passive, strained, or active work situation, as well as a combination of high social support and active work situation, were associated with SBS. In conclusion, measurements of personality and psychosocial work environment could be of value in future studies on environmental syndromes. Moreover, the demans-control-support model can predict SBS, but in a more complex way than indicated by earlier research. </p>

<p>Human papillomavirus type 16 (HPV-16) is the major causative agent of cervical cancer. The life cycle of this oncogenic DNA tumour virus is strictly associated with the differentiation program of the infected epithelial cells. Expression of the viral capsid genes L1 and L2 can only be detected in the terminally differentiated epithelial cells. The studies here focus on the regulation of HPV-16 late gene expression, which is under tight regulation. </p><p>Our experimental system consisted of almost the full length HPV-16 genome driven by a strong CMV promoter. This plasmid and mutants thereof could be transfected into HeLa cells and RNA levels monitored. Using this system, we identified an hnRNP A1-dependent splicing silencer between positions 178 and 226 of the L1 gene. This silencer inhibited the use of the 3' splice site, located immediately upstream of the L1 AUG. We speculate that this splicing silencer plays an essential role in preventing late gene expression at an early stage of the viral life cycle. We subsequently identified a splicing enhancer located in the first 17 nucleotides of L1 that may be needed to counteract the multiple hnRNP A1 dependent splicing silencers in the L1 coding region. A 55kDa protein specifically bound to this splicing enhancer. We also demonstrated that binding of the cellular factors to the splicing silencer in the L1 coding region had an inhibitory effect on expression from L1 cDNA expression plasmids.</p><p>The HPV-16 genome is divided into the early region and the late region, separated by the early poly(A) signal (pAE). pAE is used preferentially early in infection, thereby efficiently blocking late gene expression. We demonstrated that a 57 nucleotide U-rich region of the early 3’untranslated region (3’eUTR) acted as an enhancing upstream element on the usage of pAE. We demonstrated that this U-rich region specifically interacts with hFip1, CstF-64, hnRNP C1/C2 and PTB, suggesting that these factors were either enhancing or regulating polyadenylation at the HPV-16 pAE. </p><p>In conclusion, two regulatory RNA elements that both act to prevent late gene expression at an early stage in the viral life cycle and in proliferating cells were identified: a splicing silencer in the late region and an upstream u-rich element at the pAE.</p>

<p>Oral complications and symptoms are common among patients with cancer. The aim of this thesis is to study several aspects of oral status, oral health and its relation to quality of life, and oral care among patients treated with radiotherapy or chemotherapy. Descriptive, comparative and correlational designs were used. </p><p>A series of consecutive patients admitted to a university hospital or a regional hospital to receive radiotherapy for head and neck cancer or chemotherapy for haematological malignancies, were studied prospectively with regard to oral symptoms and their relation to health-related quality of life using interviews and questionnaires, examination of the oral cavity and saliva tests. All nurses and enrolled nurses who worked with these patients or with patients with lung cancer were interviewed about their education and knowledge in oral care and performed oral care. The medical and nursing records on patients with these cancer diseases at the two hospitals were reviewed. </p><p>The results indicate that patients receiving radiotherapy experienced increasing oral symptoms, which remained to a large extent one month after treatment. Patients receiving chemotherapy did not experience oral symptoms to the same extent. The oral symptoms were significantly related to patients' health-related quality of life, particularly among those receiving radiotherapy. Data also indicate that there is a lack of adequate education and continuing education in oral care among nursing staff. All patients were not examined orally before or during treatment, nor did they receive sufficient information or instruction related to oral hygiene. Patient compliance with oral hygiene procedures was acceptable, although some patients reported difficulties. Oral status and oral care were insufficiently documented, particularly in nursing records. The attitudes to oral examination and discussion on oral hygiene differed between nursing staff and patients. Nursing staff objected to examining the oral cavity referring to patient integrity. This was not considered as a hindrance among patients. In conclusion, oral health is related to health-related quality of life, which motivates a multi-disciplinary approach to oral care. </p>

<p>Bronchial carcinois are subdivided into typical and atypical. Atypical carcinoids are more malignant, but typical carcinoids may also influence survival. In the present study immunohistochemistry was performed to identify prognostic markets in patients with typical bronchial carcinoids. The diagnostic efficacy of octreoscan was evaluated, in comparison with CT and bone scan, and finally our experience of treating patients with metastatic bronchial carcinoids is reported. In an unselected material of 43 patients with typical bronchial carcinoids, metastatic disease was found in 12 patients (28%). Five patients (12%) developed distant metastases and died from their disease. High Ki-67 index, as well as positive staining for bcl-2 or p53 was associated with de- creased survival time. Positive staining for CD44s, v7-8 and v9, as well as positive nuclear staining for nm23 correlated to decreased mortality. Staining for CD44 and Ki-67 should be performed routinely for prognostic evaluation in these patients. </p><p>Octreoscan positive tumors were found in altogether 20/28 patients (71%). The primary tumor was detectable in 81% and intrathoracic metastases in 78% of the patients on octreoscan; the corresponding figures for CT were 94% and 89% respectively. Liver metastases, as shown by CT, were demonstable by octreoscan in 64% of patients. Octreoscan showed 70% and bone scan 90% sensitivity for identification of bone metastases. </p><p>Plasma chromogranin A was elevated in 28/30 patients (94%) with metastatic bronchial carcinoids and was the most sensitive tumor marker. Increased urinary 5'HIAA was found in 68%. </p><p>Biotherapy with α-interferon and Octreotide relieved carcinoid syndrome in 7/16 patients. However, only 4/27 patients showed stable disease during median 15 months, while 23 patients progressed. Treatment with cisplatinum + etoposide resulted in an objective response or stable disease for 6-8 months in 3/8 patients with widespread tumors. Doxorubicin combined with streptozotocin or paclitaxel was associated with stable disease for 9 months in 2/2 patients each. All 7 patients treated with streptozotocin+5-FU progressed. </p><p>Among the 43 unselected typical bronchial carcinoid patients, 5-year and 10-year survival was 95% and 91%, respectively. The prognosis in patients with bronchial carcinoids showing distant metastases was poor: 5-year survival was 70% from diagnosis and 22% from treatment start. </p>

<p>Postal work is performed in very different settings, and the works are e.g., drivers, letter carriers, postal sorters, and counter clerks. A finding that a small group of parcel sorters with a good psychosocial work situation had much lower health complaints than comparable workers with a worse psychosocial situation at work, indicated that it might be possible to improve mental and physical health among postal employees by improving work organization.</p><p>The theoretical framework for this thesis is the demands-control-support (DCS) model by Karasek, Theorell, and Johnson. Two cross-sectional studies were performed with questionnaires. In a study on 144 workers at a postal terminal it was found associations between low support from superiors and high psychological work demands, on one hand and gastrointestinal and sleep problems on the other. In another study on 655 postal workers in 6 different occupations, high psychological work demands and low skill discretion was associated with low-back pain, and low social support at work with neck pain. In this study, the associations differed significantly between men and women.</p><p>A follow-up study on the postal terminal (136 persons) was performed 8 and 12 months after an organizational change took place. The changes were aimed at improving the shift system, and psychosocial work situation. Authority over decision and skill discretion increased, and sick-leave decreased during the follow up period. Changes in contact with superiors, team-mates, and skill discretion were associated with changes in gastrointestinal and sleep complaints. In another follow up study, 82 individuals were studied before and 1 year after improvement of the psychosocial work environment. Musculoskeletal complaints were significantly reduced in the intervention group but not in the control group. Increased support from superiors was associated with less symptoms. Younger age and higher authority over decisions at baseline was associated with reduced symptoms at follow-up.</p><p>The main findings of this thesis are that there are significant associations between psychosocial work situation among postal workers and psychosomatic and musculoskeletal symptoms, and that it is possible to reduce symptoms and sick-leave, by changes of organization, and improvement of the psychosocial work situation </p>

<p>Enterovirus (EV) infections have been associated with the pathogenesis of Type 1 Diabetes (T1D). However, the pathway(s) by which EV may induce or accelerate diabetes is not well understood. The purpose of this thesis was to obtain new information on the mechanism by which EV infections, with different strains of EV, could cause damage to the insulin-producing β-cells in isolated human islets and in a rat insulin-producing cell line (RINm5F). </p><p>Infection with EV strains isolated from T1D patients revealed replication/cell destruction in human islets and EV-like particles in the cytoplasm of the β-cell and infection with the isolates affected the release of insulin in response to glucose stimulation as early as three days post infection, before any decrease in cell viability was observed. A decrease in the induction/secretion of the chemokine RANTES in human islets during EV infection was also detected. When islets were cultured with nicotinamide (NA) the secretion of RANTES was increased irrespectively if the islets were infected or not. In addition, the degree of virus-induced cytolysis of human islets was reduced by NA, suggesting an antiviral effect of NA. Infection with EV strains revealed permissiveness to islet-derived cells. </p><p>All EV strains used for infection were able to replicate in the RIN cell clusters (RCC) but not in the RIN cells that were cultured as a monolayer. This might be due to the differences in expression of the Coxsackie-adenovirus receptor (CAR), which only could be detected on the RCC. Infection of RCC with a CBV-4 strain did not affect cell viability and did not induce nitric oxide (NO) production alone or with the addition of IFN-γ. This was in contrast to the results obtained with synthetic dsRNA, poly(IC), which induced NO, suggesting that synthetic dsRNA does not mimic enteroviral intermediate dsRNA.</p><p>During analyses performed with the samples from a family where the mother and one son where diagnosed with T1D on the same day, the results showed that the whole family had a proven EV infection at the time diagnosis.</p><p>To conclude, the ability of EV strains to replicate in RIN cells is dependent on the growth pattern of the cells and this may be due to the upregulation and/or changed expression pattern of CAR in these cells. In the RIN cells, contrary to artificial dsRNA, viral dsRNA does not induce NO. The isolated EV virus strains used were able to infect and affect human pancreatic islets in vitro. The chemokine RANTES is reduced during an EV infection of human pancreatic islets and NA causes upregulation of RANTES in infected and uninfected islets. </p>

<p>The aim was to contribute to the optimal use of the resting ECG by exploring, in middle-aged and elderly men, the development and regression of ECG abnormalities; the prognostic value of the ECG for cardiovascular disease compared to conventional risk factors; and the impact of age at baseline and follow-up time for prediction of cardiovascular disease.</p><p>It was based on the Uppsala Study of Adult Men cohort that was started in 1970. Participants were examined at ages 50, 70, 77, and 82, with annual updates on mortality and in-hospital morbidity using national registries. </p><p>The studies indicated that the prevalence of silent MI and frequency of regression of major Q/QS patterns may be higher than previously believed. Considering that persistent T wave abnormalities and ST segment depression carried twice as high a risk for future cardiovascular disease (CVD) mortality as new or reverted abnormalities, the results suggested that serial electrocardiograms (ECG) would contribute to proper risk assessment. Also, the inclusion of ischemic ECG findings significantly increased the predictive power of the Framingham score at age 70 for CVD. </p><p>While hypertension and dyslipidemia were consistent long-term risk factors for myocardial infarction at ages 50 and 70, the length of follow-up period and age at baseline affected the predictive power of ECG abnormalities, fasting insulin, BMI, and smoking. </p><p>For stroke, midlife values for blood pressure and ECG abnormalities retained prognostic value over long follow-up periods, even though they improved when re-measured in elderly participants. ApoB/apoA1 ratio, driven by apoA1, was associated with stroke in elderly but not middle-aged men. Hyperinsulinemia and diabetes mellitus were more specifically associated with ischemic stroke than with any-cause stroke. </p><p>In summary, the resting ECG carried prognostic information beyond conventional risk factors. Even though the low prevalence of ECG abnormalities at the age of 50 calls into question the role of the ECG as a screening tool, the additional risk information it carries with it justifies its regular and repeated registration above the age of 50. </p>

<p>The aim was to study the prevalence of asthma, eczema, allergy and respiratory symptoms among pupils in Shanxi province, China, in relation to home and school environment and outdoor air pollution. In one study there was a low prevalence of self-reported asthma, eczema and pollen or pet allergy among pupils (9-20y). Rural childhood and consumption of fruit and fish were negatively associated with asthma or allergy, while current urban residency and consumption of hamburgers tended to be risk factors. In another study in junior high school pupils, similar low prevalence of asthma and allergy was found. Compared with pupils at the same age in Uppsala, Sweden, asthma and allergy were less common while daytime attacks of breathlessness were more common in Chinese pupils. Parental asthma or allergy was a predictor of asthma symptoms. Factors in the home environment such as new floor, new furniture and ETS exposure were risk factors for asthma symptoms. Crowdedness, dust amount, CO₂, temperature and air humidity were negatively associated with respiratory symptoms. Microbial chemical components like muramic acid and ergosterol, markers for bacteria and fungi, were negatively associated with wheeze or daytime attacks of breathlessness. The associations with endotoxin varied depending on the length of 3-hydroxy fatty acids of the lippopolysaccharides (LPS). Among outdoor air pollutants, SO₂ and formaldehyde were positively associated with asthma symptoms or respiratory infections. In addition, indoor SO₂, NO₂ and formaldehyde were positively associated with asthma symptoms and respiratory infections. In conclusion, rural childhood and dietary factors can be protective for asthma and allergy. ETS and chemical emissions from new material at home can be risk factors for asthmatic symptoms. In the school environment, factors of indoor origin seemed to be generally protective for respirator symptoms while factors of outdoor origin seemed to be risk factors.</p>