One way to study the stressfulness of childbirth is to examine the output of stress hormones. In this study, urinary catecholamines and salivary cortisol from 50 primiparous women were collected for 1 day during gestational weeks 37 to 39, hourly during labor and delivery, and 2 hr and 2 days postpartum. All three stress hormones increased statistically significantly from pregnancy to labor. The increase in adrenaline and cortisol was more than 500%, and the increase in noradrenaline was about 50%. After labor, the output decreased but not statistically significantly below the levels during late pregnancy. Hormone levels during late pregnancy, during labor and delivery, and during the period postpartum mostly did not correlate systematically. However, noradrenaline and adrenaline, as well as adrenaline and cortisol, were positively correlated during labor. After administration of epidural analgesia, there was a moderate but significant decrease in noradrenaline and adrenaline, whereas cortisol did not change. In conclusion, the results of this study support the assumption that childbirth is a very stressful event and that the stress responses vary considerably among women. The substantial increase of adrenaline and cortisol compared with noradrenaline indicates that mental stress is more dominant than physical stress during labor.

Background. The aims of the present study were to compare primiparous and multiparous women’s experiences of fear of delivery during an early stage of active labor (cervix dilatation 3–5 centimeters) and to study whether fear of delivery, measured during the early stage of active labor, was a predictor of the amount of pain relief received during the remaining part of labor (cervix dilatation 5 cm – partus), of the duration of the remaining part of labor, and of the occurrence of instrumental vaginal delivery and emergency cesarean section.

Method. Thirty-five primiparous and 39 multiparous women answered the Delivery Fear Scale (DFS) once during the early stage of labor and before they had received any pain relief.

Results. Primiparous women reported higher levels of fear than multiparous women did. Fear during the first phase of labor predicted only the total amount of pain relief received during labor.

Conclusion. The clinical implications of the study are that the delivery staff should consider women’s fear during labor and pay attention especially to primiparous women’s increased risk of higher levels of fear during an early stage of active labor, as compared with multiparous women’s. The challenge for staff of a delivery ward is to support the woman in labor in a way that decreases fear, which in turn might reduce the woman’s need of pain relief.

The occurrence of sickness absence in relation to gender, occupation, age, pregnancy and parenthood was analysed in a Swedish county. Data on all new sick-leave spells exceeding 7 days in the county of Östergötland (400,000 inhabitants) were recorded in 1985-1987. Information on diagnoses, occupation, age, gender, number of children etc. for each of the 45,000 persons sicklisted/year were included in the database. Incidence measures were obtained using census data as denominator.

The largest and most consistent variation in occurrence of sickness absence concerned occupation and gender, When categorising the occupations according to degree of gender-segregation, women in the extremely maledominated group (>90% men) had exceptionally high sick-leave rates, while both men and women in the group of gender-integrated occupations had significantly lower sick-leave rates. These variations with male-and female domination of occupational groups were found for sickness absence in general as well as for sick-leave due to pregnancy-related diagnoses. Men with custody of young children had the lowest sickness absence, young women in the same situation the highest, while there were no gender differences in persons without young children. Sickness absence due to pregnancy-related diagnoses varied to a large degree with occupation, but was still high in occupations with a generally low sickness absence, and increased much more than in any otherdiagnostic group over the three years. About half of the gender differences in sickness absence could be explained by sickness absence among pregnant women.

In conclusion, the occurrence of sickness absence was associated with gender, age, occupation, gender segregation of occupation, pregnancy and parenthood. Further research should focus on etiological studies and intervention trials.

During the past decades, the focus of outcome studies in chronic diseases such as rheumatoid arthritis (RA) has changed from a technical and biological preoccupation towards a more patient-concemed psychosocial perspective. The changing paradigm of chronic disease impact has been conceptualised in a number of self-report health status and outcome measurements that have been called 11one of the primary achievements of rheumatology in the 1980s". The overall aim of the study was to make a broad elucidation of the perceived selfMreported impact of rheumatoid arthritis in a representative group of individuals from a health care district, with regard to treatment and care, quality oflife, coping and well-being.

A total of 321 patients from a health care district in the northern part of Kalmar county, Sweden, with both early/mild and more severe disease were enrolled in the first part of the study, in which the medical records of these individuals were scrutinised for information about previous treatment and care. In the second part of the study, 222 of the initial 321 persons participated in an extensive postal survey exploring perceived impact of RA by self-report.

The uncertain outcome of RA disease was emphasised by a high frequency of discontinuations of drug therapy due to lack of effect or side-effects. Underlining the lack of a medical cure for RA, more than 40% of the individuals had undergone some kind of surgical procedure due to the disease. The rehabilitation services to individuals with RA appear to be functioning fairly adequately since those still working were employed in administrative work rather than in production. The participants indicated a preference for a good reception by health care workers rather than technically correct care. Only a minority of the patients who had been treated as in-patients felt that they had been involved in the planning of the care. Also, the physicians seemed to underestimate the patients desire for information concerning both medical and social aspects of the disease.

Quality of life scores exhibited a change for the worse with increasing self-reported functional disability. Physical, psychological and social life domains were fairly highly interrelated and all revealed lower levels with increasing self-reported functional disability. Also, lower levels of well-being were closely associated with a more severe RA disease, in particular loneliness, indolence, tension, security, future-orientation and endurance. Coping and wellMbeing were only weakly interrelated, but individuals who declared an active lifostyle exhibited a better well-being with a higher basic mood, greater fotureorientation and less indolence, loneliness and inferiority. Individuals accepting the RA disease displayed less guilt and tension, and greater endurance and basic mood.

The study depicts how individuals with RA in a health care district are provided with both the basic treatment and more specialised care in a collaboration between medical and surgical specialists. In general, satisfaction with the care provided was more closely related with clinical signs rather than self-reported functional performance, although the latter might more adequately reflect the perceived need of the patients. Thus, the results support the application of self-reported functional disability assessment in routine clinical rheumatological practice. The study displays methods that measure and quantify the increasing negative psychosocial impact of RA with increasing functional disability. Some evidence was also found supporting the inclusion of coping enhancement elements in health care programmes targeting patients with RA. Consequently, the inclusion of counselling enhancing acceptance of the RA and encouraging decisions about new relevant goals might, at least theoretically, increase well-being in patients with RA.

Every year, drivers throughout the world are killed or injured in road traffic, particularly in developing countries. Young drivers run a greater risk everywhere, and this problem is still largely unsolved. Better understanding of the underlying processes could, however, be a useful tool in preventive endeavours. The aim of this thesis is to elucidate some of the accident problem among young car drivers. The focus is on understanding how lifestyle and other social and demographical factors influence the health of young people in terms of mobility and safety. Better knowledge of these factors makes it possible to design safety measures specially tailored for different subgroups. This is expected to help make the measures more effective and reduce the conflict between mobility and safety.

The thesis is based on five studies, the first of which focuses on the factors that influence young people in their decision concerning whether or not to obtain a driving licence (Paper I). In the second study, focus lies on how groups with different lifestyles and socio-economic background start practice driving and the benefit derived from the opportunity to practise from the age of 16 (Paper II). The third study aims at visualising accident patterns during driving practice (Paper III) while the fourth evaluates the effects of a reform that lowered the age limit for practice driving to 16 (Paper IV). The last study aims at analysing the relation between the lifestyles of young drivers and accidents (Paper V).

The results of the five studies underlines the complexity of the young driver problem. Many factors such as financial means, time and norms influence how many people take their licence and consequentially, safety and health (I). Socio-economic background together with lifestyle influences the possibility of obtaining a driving licence and of accumulating extensive driving practice (II), which is relevant as regards safety on the road for newly qualified drivers (IV). Paper III shows the prevalent accident pattern during driver training and Paper V shows that the accident risk is different in different lifestyle groups.

The combined results presented in the five papers offers the possibility of developing different countermeasures for the selective influencing of different groups under different conditions. If this is adapted as closely as possible to target groups and situations, it should be possible to significantly enhance safety without losing much of young drivers’ mobility, both during driving practice and afterwards.

Both epidemiological and experimental studies have indicated that the ubiquitous herpesvirus Epstein-Barr virus (EBV) plays a role in the pathogenesis of multiple sclerosis (MS). Some features of MS epidemiology, such as the decline in risk among migrants from high to low MS prevalence areas, suggest the presence of variant EBV strains that increase MS risk. The objective of this study was to investigate whether genetic variability in EBV is associated with MS. Genes encoding for two EBV antigens (EBNA1 and BRRF2) were sequenced in EBV isolates from 40 MS patients and a similar number of control subjects. These viral antigens were chosen for analysis because they are known to stimulate atypical immune responses in MS. Extensive sequence polymorphism was observed within the EBNA1 and BRRF2 genes in isolates from both MS patients and controls. Interestingly, several single nucleotide polymorphisms within the EBNA1 gene, and one within the BRRF2 gene, were found to occur at marginally different frequencies in EBV strains infecting MS patients versus controls. Although this study does not find a simple causal relationship between EBV strains and the occurrence of MS, the existence of haplotypes that occur at different frequencies in MS patients versus controls may provide an area for future study of the role of EBV strain variation in multiple sclerosis.

The aim of the study was to provide a standardisation of self-reported competencies and emotional/behavioural problems among Swedish adolescents, using the Youth Self-Report (YSR). The YSR was completed by 2522 adolescents aged 13-18 years, recruited from secondary and upper secondary schools in different regions in Sweden. The results showed that effects of gender and age were small but significant with girls scoring higher than boys on most problem scales, and 15- to 16-year-olds scoring higher than younger and older adolescents on the problem scales. Small effects were also found for residence as well as for parental SES. The correlations between internalising and externalising problems were 0.51 for boys and 0.49 for girls, whereas the correlation between competence and problem scores was low. We conclude that the individual variation in YSR-scores is much greater than can be attributed to factors such as gender, age, SES, or residential area. Consequently, the YSR has the potential to serve as an instrument for assessing individual adolescents' self-reported competencies and problems in Sweden. Given the almost orthogonal relation between self-reported competencies and problems, the competence scale is surprisingly little used in psychopathology research.

Background

The ethical issue of foregoing life-sustaining treatment for newborn infants at high risk of death or severe disability is extensively debated, but there is little information on how physicians in different countries actually confront this issue to reach end-of-life decisions. The EURONIC project aimed to investigate practices as reported by physicians themselves.

Methods

The study recruited a large, representative sample of 122 neonatal intensive-care units (NICUs) by census (in Luxembourg, the Netherlands, and Sweden) or stratified random sampling (in France, Germany, the UK, Italy, and Spain) with an overall response rate of 86%. Physicians' practices of end-of-life decision-making were investigated through an anonymous, self-administered questionnaire. 1235 completed questionnaires were returned (response rate 89%).

Findings

In all countries, most physicians reported having been involved at least once in setting limits to intensive care because of incurable conditions (61–96%); smaller proportions reported such involvement because of a baby's poor neurological prognosis (46–90%). Practices such as continuation of current treatment without intensification and withholding of emergency manoeuvres were widespread, but withdrawal of mechanical ventilation was reported by variable proportions (28–90%). Only in France (73%) and the Netherlands (47%) was the administration of drugs with the aim of ending life reported with substantial frequency. Age, length of professional experience, and the importance of religion in the physician's life affected the likelihood of reporting of non-treatment decisions.

Interpretation

A vast majority of neonatologists in European NICUs have been involved in end-of-life limitation of treatments, but type of decision-making varies among countries. Cultur-related and other country-specific factors are more relevant than characteristics of individual physicians or units in explaining such variability.

Background: The protective effect of breast milk against atopic manifestations in infancy, i. e. atopic eczema and food allergy, has been controversial for the last decades. Differences in the composition of human milk could explain these controversies.

Aims: To investigate the composition of milk antibodies, such as lgE, total S-IgA and S-IgA antibodies against food and inhalant allergens (B-lactoglobulin, ovalbumin and cat allergen) in milk from atopic and non atopic mothers. To study human milk nucleotide, polyamine and polyunsaturated fatty acid (PUFA) composition. Furthermore, the composition of these factors in maternal milk were related to the development of allergic disease in the children during the first 18 months of life.

Methods: One hundred and twenty (120) children were followed at 3, 6, 12 and 18 months of age. Blood samples were obtained at birth and at 3 months. Skin prick tests were petformed at 6, 12 and 18 months and the development of atopic diseases was assessed in the children. Breast milk samples were collected from their mothers at birth and monthly dming the lactation period. Total IgE antibodies were measured by RIA and S-IgA antibodies by ELISA. Milk nucleotides and polyamines were measured by HPLC and PUFA by gas chromatography.

Results: Total IgE and total S-IgA levels were similar in colostrum from atopic and non atopic mothers, Total S-IgA levels were, however, lower in mature milk from atopic than from non atopic mothers. Levels of S-IgA antibodies against foods and cat, were similar in the two groups during the lactation period, except for low levels of anti-OVA S-lgA in colostrum of atopic mothers. Nucleotide composition was similar in milk from atopic and non atopic mothers. Low levels of putrescine and spermine were, however, found in mature milk from atopic mothers.

Low levels of LA, LNA, n-6 LCP and n-3 LCP and particularly higher LAILNA and AA!EPA ratios were found in milk from atopic mothers at one month of lactation. Correlations between individual LCP levels were observed in milk from non atopic mothers. These correlations were absent in milk from atopic individuals, indicating a disturbed PUFA metabolism. The differences were less obvious in serum phospholipids from newboms.

Total lgE, total S-IgA and S-IgA antibodies against foods and cat, as well as nucleotide and polyamine levels were similar in milk from mothers of allergic children. Lower levels of EPA in transitional milk and lower levels of EPA, DPA and DHA (p<0.05 for all) in mature milk were found in mothers of allergic as compared to mothers of non allergic children. Total n-6/total n-3 and AA/EPA ratios were low in both transitional and mature milk from mothers of allergic children. The disturbed correlations within the n-6 fatty acids in milk from atopic mothers were not related to the development of atopy in the children. In contrast, C20:4 n-3 correlated well to most of the n-6 fatty acid levels only in milk from non atopic mothers of non atopic children.

The PUP A levels in serum from allergic and non allergic children were similar, except higher levels of C22:4 n-6 and C22:5 n-6 (p<0.05 for both) and higher AA!EPA ratio in serum phospho1ipids from the former group (p<0.05). Changes in levels of milk PUFA were reflected in changes in PUFA serum phospholipids, particularly for the n-6 PUPA. The AA!EPA ratio in maternal milk was related, however, to the AA/EPA only in serum from non allergic children, while this was not the case in allergic children.

Conclusion: Low levels of anti-QV A S-IgA antibodies in colostrum and low levels of total S-IgA, putrescine and spermine in mature milk. were related to maternal atopy. Human milk IgE antibody and nucleotide composition were not related to maternal atopy. Neither of these milk factors were, however, related to development of anergic disease in children. Low levels of n-6 and n-3 PUFA in transitional milk were related to maternal atopy, particularly low levels of n-3 PUP A and high AA/EPA ratio in maternal milk and serum phospholipids in the infants were related to the development of allergy in the children. The milk PUPA composition influenced the composition of PUPA in serum phospholipids of the children. The findings are suggested to be partly related to a 8-6 desaturase dysfunction in atopic individuals.

The majority of previous studies have demonstrated a correlation between diagonal earlobe creases (ELC) and coronary artery disease (CAD).In this study of 520 forensic autopsy cases, the earlobes were studied and photographed before autopsy, and the existence of a diagonal ELC was noted in 55%. The cause of death, the degree of coronary atherosclerosis, aortosclerosis, and cerebrosclerosis, as well as heart, kidney, and spleen weights, were noted in each case. The body mass index (BMI), thickness of abdominal fat, baldness, and excessive hair in the meatus externa of the external ears were also assessed. Nonparametric methods were used in the statistical calculations.It was found that ELC was strongly correlated with CAD in both men and women (P < 0.0001) but with sudden cardiac death (SCD) only in men (P < 0.04). The sensitivity of the ELC sign was 75% and the positive predictive value (ppv) was 68%. In individuals below 40 years, the ppv was as high as 80%. Using multiple logistic regression analysis, ELC was found to be the strongest independent risk factor for CAD and SCD apart from age and BMI (both genders), as well as baldness and hair in the meatus externa (in males).It is concluded that in a patient population similar to that in the present study the ELC sign could be especially useful in screening for premature CAD in younger individuals. Copyright © 2006 by Lippincott Williams & Wilkins.

The primary objective of this study was to investigate if detection of apoptosis in the heart can be used to diagnose early myocardial ischaemia. The material consisted of myocardial tissue from autopsy cases: 10 cases with occlusive, thrombotic coronary artery disease and acute myocardial infarction, 10 cases of sudden cardiac death without coronary artery disease (CAD) and 8 controls without cardiovascular disease and with known causes of death. Necrotic changes in the myocardium were detected with hematoxylin-erythrosin-saffron, Mallory's PTAH stain and with antibodies against complement 9. Apoptotic nuclei were visualised with two different kits using the terminal deoxynucleotidyl transferase-mediated desoxyuridinetriphosphate nick end-labeling (TUNEL) method on histological sections. In the patients with CAD, early myocardial infarction was found in one defined area of the ventricular wall, apoptotic myocyte nuclei were observed not in the necrotic lesions, but evenly spread usually without a gradient, all over the myocardium with a mean number per high power field of 29% (range 3-56%) of the total number of myocyte nuclei. In the sudden cardiac deaths without CAD, necrosis was scarce and distributed both focally and irregularly in both the left and right ventricular walls. With few exceptions, the percentage of apoptotic myocyte nuclei exceeded 20% in all sections (mean 24%, range 0-68%). No difference was seen between patients with CAD and those without CAD (p > 0.05). With the TUNEL method, positively stained nuclei were seen very early and extensively all over the myocardium. It is not certain that they represent true apoptosis induced by ischemia, but TUNEL appears to be a useful screening method in cases where sudden cardiac death is suspected.

Torture is common today and is practised in over 100 countries according to Amnesty International. A substantial number of refugees coming to Europe have been tortured including females. Documentation of physical injuries due to torture is done by forensic pathologists often in collaboration with psychiatrists. In Sweden, the majority of torture documentations is done by an organization (KTC) which have specialized in documenting torture, and in short-term therapy of refugees and other crime victims suffering from post-traumatic stress. From the KTC archives of 500 documented alleged torture victims, the records of 63 females were studied separately. Age, nationality, asylum motive, social situation, torture methods, number of injuries, and sequels to torture were among the variables studied. Female torture victims differed from their male counterparts studied previously in the following: (i) The most common reason for seeking asylum was persecution because of the political activity of their husbands or some other close relative. (ii) Rape often both anal and vaginal, several times, and by different persons, was reported by 76% of the women. Physical abuse by use of blunt force was alleged by 95% but (iii) other types of force and specific torture methods was reported infrequently. (iv) A high frequency of PTSD - 87% was diagnosed. © 2007 Elsevier Ltd and FFLM.

A case of sudden infant death with histiocytoid cardiomyopathy and ventricular non-compaction was investigated with immunohistochemical methods. Histiocytoid cardiomyopathy is thought to be a developmental defect of the cardiomyocytes of the conduction system. In contrast to mature cardiomyocytes, the histiocytoid cells showed only weak reactions to desmin and myosin antibodies. They lacked cross-striation but reacted strongly to enolase and myoglobin antibodies. The protein Pax-7, seen only in cells undergoing differentiation, and the proliferation marker Ki-67 were not expressed in the histiocytoid cells. In areas of altered myocardium, clusters of CD4-, CD8-, and CD68-positive inflammatory cells were seen as well an abundance of mast cells. With the TUNEL method, it was found that many of the histiocytoid cells were undergoing apoptosis. Our results confirm that the histiocytoid cells are defective cardiomyocytes. The apoptotic and inflammatory changes point to a degenerative process rather than defective maturation of cardiomyocytes as has been suggested in some earlier studies. Ventricular non-compaction is a developmental defect of the subendocardial tissue with hypertrabeculation and weak development of the papillary muscles. Only one case combined with histiocytoid cardiomyopathy has been described previously. A causal connection between the two conditions cannot be established until more cases have been analyzed.

Background: In 1994, the mortality in coronary heart disease was four times higher among Lithuanian middle-aged men than among Swedish men. Over the period 1993-1995, the LiVicordia study investigated possible causes for this difference. We have earlier reported lower serum levels of cholesterol and higher susceptibility of low-density lipoprotein cholesterol for oxidation among Lithuanian men. Objective: In this part of the study, the aim was to compare mean estimates of food intake. Design: Cross-sectional study of random samples of 50-year-old men from each of the cities of Link÷ping, Sweden and Vilnius, Lithuania (n=150). The volunteers were interviewed about their food intake with the 24-hour recall method. Results: We found no differences in total energy intake, but Vilnius men had a higher energy intake from fat. Vilnius men consumed more fat from meat and less vegetable fat, while fat intake from dairy products was almost the same. Also, Vilnius men had a higher intake of vegetables, while Link÷ping men had a higher intake of fruit and berries. Conclusion: The observed differences in food consumption and dietary composition are partly consistent with the higher CHD mortality among Lithuanian men. However, data on biomarkers indicate that other dietary and lifestyle factors play a role.

The aim of the present study was to develop a PCR-based method to detect and identify fungi directly from human venous blood. We used broad-range PCR primers that targeted a part of the large subunit 28S rRNA genes. To obtain species-specific hybridisation probes, type strains of Candida albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis and Cryptococcus neoformans were PCR amplified, and the amplicons were analysed by gene sequencing. Based on the sequence analysis, species-specific probes that targeted variable regions were designed and used in hybridisation analyses. Between 2 to 10 fungal cells/ml of spiked blood samples could be detected and correctly identified to species. We applied the technique to blood samples obtained from two patients with or two patients without verified candidaemia. The three samples of candidaemia patients were correctly identified to species level, and those of the negative patients remained negative. This method is a potential tool for diagnosis of systemic invasive candidiasis.

Background: The transport mobility of children and adolescents with cerebral palsy (CP) is of vital interest for the individual, as well as for society. Enhanced transport mobility can be related to improved functional health status and a higher degree of autonomy, which in turn may reduce the demand for societal support. UN Resolution 48/96, together with Swedish legislation and "Vision Zero" have in different ways established that the transport system must be designed to meet also the needs of children and adolescents with disabilities. Hence, it is necessary to identify and eliminate obstacles hindering children and adolescents with CP from using public transport and other means of transport, such as their own cars, at the same level as other members of society. However, in the case of children and adolescents with CP, the transport situation and the learner driver's educational situation have so far been largely unknown.

Aim: The general aim of the thesis was to describe and analyse, from a legislative and a public health perspective, the transport mobility situation for children and adolescents with CP. Furthermore, the general aim was to identify obstacles for the target group to use public transport and other means of transportation, at the same level as other members of the society, and to suggest improvements that will remove the identified obstacles.

Material and methods: Several different data collection methods were used. Data, concerning travel habits and parents' perceived risks regarding transportation, were taken from a postal questionnaire addressed to parents of children and adolescents with CP. In order to estimate the numbers of potential learner drivers with CP in each age group in Sweden, a literature review was conducted, based on Swedish material. Furthermore, logbooks for learner drivers with CP were analysed retrospectively, in order to identify procedures, problems and key tasks in their driver education. Visual search strategies for learner drivers with CP were analysed, utilizing an eye tracker, and an attempt was made to introduce a screening tool for predicting the outcome of driver education.

Results: Children and adolescents with CP were found to be transported under unsafe conditions, causing worry among their parents. When transporting children in the family vehicle, the parents were exposed to a very heavy burden, which increased their worry. The prevalence of potential learner drivers with CP who were in need of highly specialised driver education, including individually adapted driver training vehicles, was estimated to be 0.15 per 1,000 of a population-based age group of learner drivers in Sweden. Complex procedures, structural problems and financial obstacles made it difficult for adolescents with CP to obtain a driving licence and an adapted vehicle. The total duration of the driving tuition given by a driving instructor was found to be almost nine times higher for learner drivers with CP than for non-disabled learner drivers. Visual search strategies among learner drivers with CP were found to be less flexible than among other learner drivers. This fact indicated a need for better methods of teaching such strategies to this group as an integral component of their driver education. The validity of the motor-free visual perceptual test, TVPS-UL, for predicting the outcome of driver education for learner drivers, was found to be low. In order to find a reliable and valid screening tool for this purpose, future studies should focus on cross-validation of visual perceptual and dual task performance tests for different types of independent variables, such as obtaining a driving licence or not, accident involvement and driving ability.

Conclusion: The transport system was found, from a legislative and public health perspective, to be unsuitable to meet the needs of children and adolescents with CP. Suggestions for improving transport mobility for children and adolescents with CP are provided. Several of these suggestions are practical, concrete and contextual for Swedish conditions, and some of them necessitate future research. However, a number of these suggestions are also applicable in an international context.

In order to study the importance of some less well-known occupational exposures and environmental factors in lung cancer etiology, a series of investigations were conducted in the Latium region of Italy, which includes the city of Rome. Five historical cohort studies were carried out on various occupational groups: power plant workers and merchant seamen with potential exposure to asbestos occupations with exposure to silica dust (silicotics receiving a disability compensation), and occupations withexposure to sulphuric acid mist (soap production workers) and to engine exhaust (taxi drivers). In addition, a case-control study evaluated lung cancer risk among ceramic workers exposed to silica dust, and a correlation study compared lung cancer mortality rates in areas with distinct geological features as a proxy of radon exposure in dwellings. Finally, time trends and geographical differences in lung cancer mortality rates in Italy not due to active smoking (background rates) were estimated to obtain an overall view of the aggregate effect of other factors than active smoking.

More or less clearly increased risks of lung cancer mortality were observed in the cohorts of power plant workers (SMR=ol. 8, 95% cr~D.77-3.5;9D~ cr~o.ss-3.2), and merchant seamen (SMR~1.7, 95~ CI=l.l-2. 5) 1 probably mainly due to asbestos. An excess lung cancer risk was detected among ceramic workers (OR=2. 0, 95% CI=l.l-3.5); those ceramic workers with silicosis showed an even higher relative risk (0R=3. 9, 95% CI=l. 8-8.3) . Subjects receiving a disability pension for silicosis in the region were also found to have an increased risk of lung cancer (MOR=1.5; 95% CI=l.l-1.9). There was a suggestion of excess risk of lung cancer among workers in the production of soap (SMR=1.7; 95%CI~D.55-3.9; 90~ CI~0.73-3.6), although the limited size of the study precludes any definitive conclusion. Taxi drivers in Rome also appeared to have a slightly increased risk of lung cancer (SMR~1.2, 95~ CI~D.97-1.5), especially those enrolled more recently (SMR~1.4, 95~ CI~l.02-1.9)

After adjustment for smoking and urbanization, the ecologic study showed a 20% increase in mortality rates for lung cancer in an area with a higher level of background radiation. Indoor radon exposure may be suggested as a potentially important risk factor for lung cancer in that area.

When differences of time and place in lung cancer death rates not attributable to active smoking were studied, all calculations indicated that the estimated background rates increased in Italy from the period 1956-58 to the period 1987-1989, especially in males. Higher background rates were observed in heavily urbanized areas than in rural areas.

The overwhelming role in cigarette smoking is well recognized but various environmental factors also play an important role in causing lung cancer. These factors should not be neglected in public health efforts to reduce the risk of lung cancer, especially as they may at times be easier to reduce or eliminate than smoking.

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.

Aims: To study the introduction of Haemophilus influenzae type b (Hib) vaccination in Sweden, and to identify factors promoting and inhibiting the process. Methods. The introduction of general childhood vaccination against Hib in Sweden in 1992-93 was studied using the Cultural Historical Activity Theory as a theoretical framework. Results: Five activity systems were found to be involved in the introduction process, the systems of vaccine production, government administration, news distribution, science, and disease prevention. The critical factors for introduction of the programme were found to be the vaccine product, conception of the disease, government economy and public decision-making. Conclusions: The results show that a broad range of non-biomedical aspects must be considered when a public health intervention such as a general vaccination programme is introduced.

Since 1992-1993 vaccination against Haemophilus influenzae type b (Hib) with conjugated vaccines is included in the general Swedish childhood vaccination programme. In this thesis the introduction of Hib vaccination has been evaluated.

The epidemiology and clinical spectrum of invasive H. influenzae disease was prospectively studied during the pre-vaccination period in a well-defined population of Sweden 1987-1992. The incidence (cases/100 000/personyear) was 5.9 for all ages and 55 in children 0 to 4 years of age. Serotype b was the dominating type, especially in children. Three patients died in connecting with illness and six developed permanent sequelae.

In national studies, the incidence before and after introduction of the Hib vaccination programme was compared. The source for the studies was the report system from the clinical microbiology laboratories to the Swedish Institute of Infectious Disease Control. Already within one year after introduction a decreased incidence was observed. In the prevaccination period the incidence was 34 in 0 to 4 years old children. In 1998 the incidence had decreased to 1.6 in the same age group. Thirteen children were identified with invasive Hib disease in spite of vaccination. Effectiveness, which take in account both direct and indirect effects of vaccination in 0 to 4 years old children was calculated to 96.0% (95 %Cl, 94.2-97.4). To study the impact of Hib vaccination in the on the diagnosis epiglottitis a national register of all patients treated at Swedish hospitals was used. In the age group 0-4 year the incidence decreased with 95 % after introduction of Hib vaccination. Even in older ages a decrease was observed but this trend did not reach statistically significance.

An evaluation of the economic consequences of a general childhood vaccination programme against Hib in Sweden was conducted. A retrospective prevaccination annual cohort of 0-4 year old children was compared with an annual cohort of the same age group after a completely implemented vaccination programme against Hib. The cost analysis shows that vaccination against Hib is cost saving when indirect costs are included in the analysis. In the cost-benefit analysis it is shown that society will gain -88 million Swedish Crowns annually when Hib vaccination is totally implemented.

The process of introducing general childhood Hib vaccination was studied. The critical factors for implementation of the immunisation programme were found to be the vaccine product, conception of the disease, government economy and public decision-making. Five activity systems were found to be involved in the implementation process, the systems of vaccine production, government administration, news distribution, science, and disease prevention. To structure the results a theoretical framework was used, Culture Historical Activity Theory. The study shows that a broad range of aspects must be considered before an intervention such as a general vaccination programme can be implemented in society.

This study covers the lifestyle component of the problems related to young drivers' accident risk. The purpose of the study is to measure the relationship between lifestyle and accident risk, and to identify specific high-risk and low-risk groups. Lifestyle is measured through a questionnaire, where 20-year-olds describe themselves and how often they deal with a large number of different activities, like sports, music, movies, reading, cars and driving, political engagement, etc. They also report their involvement in traffic accidents. With a principal component analysis followed by a cluster analysis, lifestyle profiles are defined. These profiles are finally correlated to accidents, which makes it possible to define high-risk and low-risk groups. The cluster analysis defined 15 clusters including four high-risk groups with an average overrisk of 150% and two low-risk groups with an average underrisk of 75%. The results are discussed from two perspectives. The first is the importance of theoretical understanding of the contribution of lifestyle factors to young drivers' high accident risk. The second is how the findings could be used in practical road safety measures, like education, campaigns, etc.

The thesis presents five different studies with the overall purpose of developing better preconditions for preventing accidents among young novice drivers. Too many young drivers are killed or injured in road accidents all over the world and we have still not succeeded in reducing their overrisk and fully understanding the interaction between the processes behind their accident involvement. The focus of the thesis is on the development of a model of the behaviour of young drivers in which different factors contributing to their accident involvement are explained. In the first study, new strategies in driver training have been developed and experimentally tested, the aim being to reduce the problems of overestimation, poor visual search patterns and unstructured teaching and training by laymen (I). In the second study, different safety measures were developed and experimentally tested with the purpose of finding the best method for reducing accidents among professional drivers (II). These two studies, combined with literature surveys, have contributed to the design of the model of young drivers' accident involvement. The suggested model is presented in paper m. The last two studies aim at deeper understanding of two specific relations in the model, the relation between training strategy and young drivers' subjective skill (N) and the relation between lifestyle and accidents (V).

The results of these studies, including the literature surveys of paper Ill, underline the complexity of the young driver problem. A structure with three main factors influencing accident involvement is suggested: the learning process, social influence and individual preconditions. Through different processes such as training and subjective skill, feedback and motives for driving, skill acquisition and automation, subjective norms or lifestyle, these factorsinfluence driving behaviour and thereby accident involvement. In the two first studies, it was shown that improved driver training, in spite of poor results from many other evaluations of driver training, may contribute to the prevention of young drivers' accident involvement. It was also found that the strategy that is chosen for driver training is important for the driver's own estimation of his skill. The wrong type of training may produce over-confident drivers.

Even if we have considerable knowledge about the factors contributing to accident involvement, we cannot yet with certainty identify the best countermeasures. We need to know more about these processes. Since there are still many unsolved problems and many processes in young driver behaviour that are not understood well enough, there is probably still a large potential for improving safety among young drivers.

Objective: We have recently shown that terminal sialic acid residues are essential for α1-acidglycoprotein (AGP)-induced Ca²⁺ mobilization in neutrophils. The aim of the present studywas to establish the importance of sialic acid-residues on AGP in modulating humanneutrophil functions, with emphasis on the generation of reactive oxygen species (ROS).Material and methods: ROS were measured by luminol-enhanced chemiluminescence inisolated human neutrophils.

Results: We found that AGP did not provoke ROS generation in resting or L-selectin presensitizedneutrophils. Moreover, AGP did not affect the N-formyl-methionyl-leucylphenylalanine(fMLP)-induced ROS generation but it slightly suppressed opsonized zymosaninducedresponses. However, when the neutrophils were pre-stimulated with fMLP, thefollowing addition of AGP provoked a marked ROS response. Dose-response studies and timestudies revealed that the ROS generating capacity of AGP was maximal at a concentration of0.05 mg/ml and when given 3-10 min after addition of fMLP. A desialylated form of AGP orpre-treatment of neutrophils with 3’- and 6’-sialyllactose caused a substantial lower ROSresponse in neutrophils pre-stimulated with fMLP.

Conclusions: Our data show that AGP can stimulate a second ROS response in fMLP preactivatedneutrophils and that terminal sialic acid residues on AGP play a crucial role in thisregard.

PURPOSE: Most men who undergo castration therapy for prostatic carcinoma will have vasomotor symptoms that usually persist for years. Vasomotor symptoms are elicited from the thermoregulatory center, possibly due to a decrease in hypothalamic opioid activity induced by low sex steroid concentrations. Acupuncture treatment in women, which stimulates hypothalamic opioid activity, alleviates vasomotor symptoms. We report on men treated with acupuncture for relief of vasomotor symptoms after castration therapy.

MATERIALS AND METHODS: We asked 7 men with vasomotor symptoms due to castration therapy to receive acupuncture treatment 30 minutes twice weekly for 2 weeks and once a week for 10 weeks. Effects on flushes were recorded in logbooks.

RESULTS: Of the 7 men 6 completed at least 10 weeks of acupuncture therapy and all had a substantial decrease in the number of hot flushes (average 70% after 10 weeks). At 3 months after the last treatment the number of flushes was 50% lower than before therapy. Therapy was discontinued after 10 weeks because of a femoral neck fracture in 1 man and after 3 weeks due to severe back pain in 1.

CONCLUSIONS: Acupuncture may be a therapeutic alternative in men with hot flushes after castration therapy and merits further evaluation.