Epithelial sodium channel in airway epithelium of the newborn infant : Implications for postnatal pulmonary adaptation

The aim of the present thesis was to study the role of the epithelial sodium channel (ENaC) in clearance of fetal lung fluid in the newborn infant by measurement of airway epithelial expression of ENaC, of nasal transepithelial potential difference (N-PD), and of lung compliance (LC). In addition, the effect of postnatal dexamethasone on airway epithelial ENaC expression was measured in preterm infants with bronchopulmonary dysplasia (BPD). The patient population was formed of selected term newborn infants born in the Department of Obstetrics (Studies II-IV) and selected preterm newborn infants treated in the neonatal intensive care unit of the Hospital for Children and Adolescents (Studies I and IV) of the Helsinki University Central Hospital in Finland. A small population of preterm infants suffering from BPD was included in Study I. Studies I, III, and IV included airway epithelial measurement of ENaC and in Studies II and III, measurement of N-PD and LC. In Study I, ENaC expression analyses were performed in the Research Institute of the Hospital for Sick Children in Toronto, Ontario, Canada. In the following studies, analyses were performed in the Scientific Laboratory of the Hospital for Children and Adolescents. N-PD and LC measurements were performed at bedside in these hospitals. In term newborn infants, the percentage of amiloride-sensitive N-PD, a surrogate for ENaC activity, measured during the first 4 postnatal hours correlates positively with LC measured 1 to 2 days postnatally. Preterm infants with BPD had, after a therapeutic dose of dexamethasone, higher airway epithelial ENaC expression than before treatment. These patients were subsequently weaned from mechanical ventilation, probably as a result of the clearance of extra fluid from the alveolar spaces. In addition, we found that in preterm infants ENaC expression increases with gestational age (GA). In preterm infants, ENaC expression in the airway epithelium was lower than in term newborn infants. During the early postnatal period in those born both preterm and term airway epithelial βENaC expression decreased significantly. Term newborn infants delivered vaginally had a significantly smaller airway epithelial expression of αENaC after the first postnatal day than did those delivered by cesarean section. The functional studies showed no difference in N-PD between infants delivered vaginally and by cesarean section. We therefore conclude that the low airway epithelial expression of ENaC in the preterm infant and the correlation of N-PD with LC in the term infant indicate a role for ENaC in the pathogenesis of perinatal pulmonary adaptation and neonatal respiratory distress. Because dexamethasone raised ENaC expression in preterm infants with BPD, and infants were subsequently weaned from ventilator therapy, we suggest that studies on the treatment of respiratory distress in the preterm infant should include the induction of ENaC activity.

Matrix proteinases in lung injury in the preterm infant

During inflammation, excess production and release of matrix proteinases, including matrix metalloproteinases (MMPs) and serine proteinases, may result in dysregulated extracellular proteolysis leading to development of tissue damage. Pulmonary inflammation may play an important role in the pathogenesis of lung injury in the preterm infant. The aims of this study were to evaluate involvement of MMPs and serine proteinase trypsin in acute and chronic lung injury in preterm infants and to study the role of these enzymes in acute lung injury by means of an animal model of hyperoxic lung injury. Molecular forms and levels of MMP-2, -8, and -9, and their specific inhibitor, tissue inhibitor of metalloproteinases (TIMP)-2, as well as trypsin were studied in tracheal aspirate fluid (TAF) samples collected from preterm infants with respiratory distress. Expression and distribution of trypsin-2 and proteinase-activated receptor 2 (PAR2) was examined in autopsy lung specimens from fetuses, from preterm infants with respiratory distress syndrome (RDS) or bronchopulmonary dysplasia (BPD), and from newborn infants without lung injury. We detected higher MMP-8 and trypsin-2 and lower TIMP-2 in TAF from preterm infants with more severe acute respiratory distress. Infants subsequently developing BPD had higher levels of MMP-8 and trypsin-2 early postnatally than did those who survived without this chronic lung injury. Immunohistochemically, trypsin-2 was mainly detectable in bronchial epithelium, but also in alveolar epithelium, and its expression was strongest in prolonged RDS. Since trypsin-2 is potent activator of PAR2, a G-protein coupled receptor involved in inflammation, we studied PAR2 expression in the lung. PAR2 co-localized with trypsin-2 in bronchoalveolar epithelium and its expression was significantly higher in bronchoalveolar epithelium in preterm infants with prolonged RDS than in newborn controls. In the experimental study, rats were exposed to >95% oxygen for 24, 48, and 60 hours, or room air. At 48 hours of hyperoxia, MMP-8 and trypsin levels sharply increased in bronchoalveolar lavage fluid, and expression of trypsin appeared in alveolar epithelium, and MMP-8 predominantly in macrophages. In conclusion, high pulmonary MMP-8 and trypsin-2 early postnatally are associated with severity of acute lung injury and subsequent development of BPD in preterm infants. In the injured preterm lung, trypsin-2 co-localizes with PAR2 in bronchoalveolar epithelium, suggesting that PAR2 activated by high levels of trypsin-2 is involved in lung inflammation associated with development of BPD. Marked increase in MMP-8 and trypsin early in the course of experimental hyperoxic lung injury suggests that these enzymes play a role in the pathogenesis of acute lung injury. Further exploration of the roles of trypsin and MMP-8 in lung injury may offer new targets for therapeutic intervention.

Mother-Infant Antibodies to Pneumococcal Polysaccharides and Proteins : Transfer and Persistence of Maternal Antibodies and Development of Vaccine-Induced and Naturally Acquired Antibodies in Infants

Symptomless nasopharyngeal carriage of Streptococcus pneumoniae (pneumococcus) is very common in young children. Occasionally the carriage proceeds into mild mucosal diseases, such as sinusitis or acute otitis media, or into serious life-threatening diseases, such as pneumonia, sepsis or meningitis. Each year, up to one million children less than five years of age worldwide die of invasive pneumococcal diseases (IPD). Especially in the low-income countries IPD is a leading health problem in infants; 75% of all IPD cases occur before one year of age. This stresses the need of increased protection against pneumococcus in infancy. Anti-pneumococcal antibodies form an important component in the defence against pneumococcal infection. Maternal immunisation and early infant immunisation are two possible ways by which potentially protective antibody concentrations against pneumococci could be achieved in early infancy. The aim of this thesis is to increase the knowledge of antibody mediated protection against pneumococcal disease in infants and young children. We investigated the transfer of maternal anti-pneumococcal antibodies from Filipino mothers to their infants, the persistence of the transferred antibodies in the infants, the immunogenicity of the 23-valent pneumococcal polysaccharide vaccine (PPV) in infants and the response of the children to a second dose of PPV at three years of age. We also investigated the development of antibodies to pneumococcal protein antigens in relation to culture-confirmed pneumococcal carriage in infants. Serum samples were collected from the mothers, the umbilical cords and from the infants at young age as well as at three years of age. The samples were used to determine the antibody concentrations to pneumococcal serotypes 1, 5, 6B, 14, 18C and 19F, as well as to the pneumococcal proteins PspA, PsaA, Ply, PspC, PhtD, PhtDC and LytC by the enzyme immunoassay. The findings of the present study confirm previously obtained results and add to the global knowledge of responses to PPV in young children. Immunising pregnant women with PPV provides the infants with increased concentrations of pneumococcal polysaccharide antibodies. Of the six serotypes examined, serotypes 1 and 5 were immunogenic already in infants. At three years of age, the children responded well to the second dose of PPV suggesting that maternal and early infant immunisations might not induce hyporesponsiveness to polysaccharide antigens after subsequent immunisations. The anti-protein antibody findings provide useful information for the development of pneumococcal protein vaccines. All six proteins studied were immunogenic in infancy and the development of anti-protein antibodies started early in life in relation to pneumococcal carriage.

Herätys kylässä ja tuvissa : Rääkkylän Oravisalon kylä ja renqvistiläinen herätys 1820-luvulla

A Revival in a Village and its Households. The Village of Oravisalo in Rääkkylä Parish and the Renqvistist Revivalism in the 1820s. My purpose is to apply the science of religion and the study of past communities to the study of religious revivalism. Revivalism will be considered a religious phenomenon as well as a cultural and social phenomenon. What makes this study unique is the possibility to reconstruct a list of participating revivalists based on entries in the communion book of the time. The conflict between the revivalists and the chaplain of Rääkkylä also generated other documentary material. The community in Oravisalo was relatively stratified. People lived in complex and varying forms of households. They also had plentiful contacts both with unrelated inhabitants of Oravisalo and with the neighbouring villages. Through these contacts the inhabitants of Oravisalo were introduced to revivalism. In Oravisalo, the revival for the most part fell into a certain social stratum and did not severely damage existing relationships within families or among acquaintances. The revivalists formed a new community within the village but the community was neither very tightly-knit nor was it closed. The revival was an individual phenomenon affected by general factors. First, there were factors that brought about a quest for an applicable system of meanings. These factors included at least three important issues: the Great Partition of land, the crisis of slash-and-burn cultivation, and a population growth that increased the proportion of the landless in the village. As a result, many of the revivalists had low status and poor expectations for the future. Second, there were factors that appealed to the people in the message and character of the preacher, Henrik Renqvist. Third, the proximity of the village to Liperi, where the revival got its start, was crucial to revivalism s spread to Oravisalo. Culturally, the revival meant a change in the system of symbols or meanings, so it was not solely a matter of intensified religious fervour. For instance, Communion, prayer, reading, and perhaps baptism symbolised different things to the revivalists than to other villagers. However, the revivalists do not seem to have started any moral revolution in their village. The religious aspect defined the limits of the protest and the resistance towards authorities. The revivalists wanted only to have the right to follow their conscience. The freedom granted the female members was limited to the religious sphere. No social or economic claims were made. The revival altered the situation of its members only on a symbolic level, yet it also offered them status within their own group.

Gustaf III inför sina undersåtar : Konsten att härska och politikens kulturhistoria

The dissertation analyses the political culture of Sweden during the reign of King Gustav III (1771-1792). This period commonly referred to as the Gustavian era followed the so-called Age of Liberty ending half a century of strong parliamentary rule in Sweden. The question at the heart of this study engages with the practice of monarchical rule under Gustav III, its ideological origins and power-political objectives as well as its symbolic expression. The study thereby addresses the very nature of kingship. In concrete terms, why did Gustav III, his court, and his civil service vigorously pursue projects that contemporaneous political opponents and, in particular, subsequent historiography have variously pictured as irrelevant, superficial, or as products of pure vanity? The answer, the study argues, is to be found in patterns of political practice as developed and exercised by Gustav III and his administration, which formed a significant part of the political culture of Gustavian Sweden. The dissertation is divided into three parts. The first traces the use and development of royal graces chivalric orders, medals, titles, privileges, and other gifts issued by the king. The practice of royal reward is illustrated through two case studies: the 1772 coup d état that established Gustav III s rule, and the birth and baptism of the crown prince, Gustav Adolf, in 1778. The second part deals with the establishment of the Court of Appeal in Vasa in 1776. The formation of the Appeals Court was accompanied by a host of ceremonial, rhetorical, emblematic, and architectural features solidifying its importance as one of Gustav III s most symbolic administrative reform projects and hence portraying the king as an enlightened monarch par excellence. The third and final part of the thesis engages with war as a cultural phenomenon and focuses on the Russo-Swedish War of 1788-1790. In this study, the war against Russia is primarily seen as an arena for the king and other players to stage, create and re-create as well as articulate themselves through scenes and roles adhering to a particular cultural idiom. Its codes and symbolic forms, then, were communicated by means of theatre, literature, art, history, and classical mythology. The dissertation makes use of a host of sources: protocols, speeches, letters, diaries, newspapers, poetry, art, medals, architecture, inscriptions and registers. Traditional political source material and literary and art sources are studied as totalities, not as separate entities. Also it is argued that political and non-fictional sources cannot be understood properly without acknowledging the context of genre, literary conventions, and artistic modes. The study critically views the futile, but nonetheless almost habitual juxtaposition of the reality of images, ideas, and metaphors, and the reality of supposedly factual historical events. Significantly, the thesis presumes the symbolic dimension to be a constitutive element of reality, not its cooked up misrepresentation. This presumption is reflected in a discussion of the concept of role , which should not be anachronistically understood as roles in which the king cast himself at different times and in different situations. Neither Gustav III nor other European sovereigns of this period played the roles as rulers or majesties. Rather, they were monarchs both in their own eyes and in the eyes of their contemporaries as well as in all relations and contexts. Key words: Eighteenth-Century, Gustav III, Cultural History, Monarchs, Royal Graces, the Vasa Court of Appeal, the Russo-Swedish War 1788–1790.

Child temperament and parental personality: continuity and transactional change

Studying the continuity and underlying mechanisms of temperament change from early childhood through adulthood is clinically and theoretically relevant. Knowledge of the continuity and change of temperament from infancy onwards, especially as perceived by both parents is, however, still scanty. Only in recent years have researchers become aware that personality, long considered as stable in adulthood, may also change. Further, studies that focus on the transactional change of child temperament and parental personality also seem to be lacking, as are studies focusing on transactions between child temperament and more transient parental characteristics, like parental stress. Therefore, this longitudinal study examined the degree of continuity of temperament over five years from the infant s age of six months to the child s age of five and a half years, as perceived by both biological parents, and also investigated the bidirectional effects between child temperament and parents personality traits and overall stress experienced during that time. First, moderate to high levels of continuity of temperament from infancy to middle childhood were shown, depicting the developmental links between affectively positive and well-adjusted temperament characteristics, and between characteristics of early and later negative affectivity. The continuity of temperament was quantitatively and qualitatively similar in both parents ratings. The findings also demonstrate that infant and childhood temperament characteristics cluster to form stable temperament types that resemble personality types shown in child and adult personality studies. Second, the parental personality traits of extraversion and neuroticism were shown to be highly stable over five years, but evidence of change in relation to parents views of their child s temperament was also shown: an infant s higher positive affectivity predicted an increase in parental extraversion, while the infant s higher activity level predicted a decrease in parental neuroticism over five years. Furthermore, initially higher parental extraversion predicted higher ratings of the child s effortful control, while initially higher parental neuroticism predicted the child s higher negative affectivity. In terms of changes in parental stress, the infant s higher activity level predicted a decrease in maternal overall stress, while initially higher maternal stress predicted a higher level of child negative affectivity in middle childhood. Together, the results demonstrate that the mother- and father-rated temperament of the child shows continuity during the early years of life, but also support the view that the development of these characteristics is sensitive to important contextual factors such as parental personality and overall stress. While parental personality and experienced stress were shown to have an effect on the child s developing temperament, the reverse was also true: the parents own personality traits and perceived stress seemed to be highly stable, but also susceptible to their experiences of their child s temperament.

Bacillus cereus spores and cereulide in food-borne illness

B. cereus is a gram-positive bacterium that possesses two different forms of life:the large, rod-shaped cells (ca. 0.002 mm by 0.004 mm) that are able to propagate and the small (0.001 mm), oval shaped spores. The spores can survive in almost any environment for up to centuries without nourishment or water. They are insensitive towards most agents that normally kill bacteria: heating up to several hours at 90 ºC, radiation, disinfectants and extreme alkaline (≥ pH 13) and acid (≤ pH 1) environment. The spores are highly hydrophobic and therefore make them tend to stick to all kinds of surfaces, steel, plastics and live cells. In favorable conditions the spores of B. cereus may germinate into vegetative cells capable of producing food poisoning toxins. The toxins can be heat-labile protein formed after ingestion of the contaminated food, inside the gastrointestinal tract (diarrhoeal toxins), or heat stable peptides formed in the food (emesis causing toxin, cereulide). Cereulide cannot be inactivated in foods by cooking or any other procedure applicable on food. Cereulide in consumed food causes serious illness in human, even fatalities. In this thesis, B. cereus strains originating from different kinds of foods and environments and 8 different countries were inspected for their capability of forming cereulide. Of the 1041 isolates from soil, animal feed, water, air, used bedding, grass, dung and equipment only 1.2 % were capable of producing cereulide, whereas of the 144 isolates originating from foods 24 % were cereulide producers. Cereulide was detected by two methods: by its toxicity towards mammalian cells (sperm assay) and by its peculiar chemical structure using liquid-chromatograph-mass spectrometry equipment. B. cereus is known as one of the most frequent bacteria occurring in food. Most foods contain more than one kind of B. cereus. When randomly selected 100 isolates of B. cereus from commercial infant foods (dry formulas) were tested, 11% of these produced cereulide. Considering a frequent content of 103 to 104 cfu (colony forming units) of B. cereus per gram of infant food formula (dry), it appears likely that most servings (200 ml, 30 g of the powder reconstituted with water) may contain cereulide producers. When a reconstituted infant formula was inoculated with >105 cfu of cereulide producing B. cereus per ml and left at room temperature, cereulide accumulated to food poisoning levels (> 0.1 mg of cereulide per serving) within 24 hours. Paradoxically, the amount of cereulide (per g of food) increased 10 to 50 fold when the food was diluted 4 - 15 fold with water. The amount of the produced cereulide strongly depended on the composition of the formula: most toxin was formed in formulas with cereals mixed with milk, and least toxin in formulas based on milk only. In spite of the aggressive cleaning practices executed by the modern dairy industry, certain genotypes of B. cereus appear to colonise the silos tanks. In this thesis four strategies to explain their survival of their spores in dairy silos were identified. First, high survival (log 15 min kill ≤ 1.5) in the hot alkaline (pH >13) wash liquid, used at the dairies for cleaning-in-place. Second, efficient adherence of the spores to stainless steel from cold water. Third, a cereulide producing group with spores characterized by slow germination in rich medium and well preserved viability when exposed to heating at 90 ºC. Fourth, spores capable of germinating at 8 ºC and possessing the psychrotolerance gene, cspA. There were indications that spores highly resistant to hot 1% sodium hydroxide may be effectively inactivated by hot 0.9% nitric acid. Eight out of the 14 dairy silo tank isolates possessing hot alkali resistant spores were capable of germinating and forming biofilm in whole milk, not previously reported for B. cereus. In this thesis it was shown that cereulide producing B. cereus was capable of inhibiting the growth of cereulide non-producing B. cereus occurring in the same food. This phenomenon, called antagonism, has long been known to exist between B. cereus and other microbial species, e.g. various species of Bacillus, gram-negative bacteria and plant pathogenic fungi. In this thesis intra-species antagonism of B. cereus was shown for the first time. This brother-killing did not depend on the cereulide molecule, also some of the cereulide non-producers were potent antagonists. Interestingly, the antagonistic clades were most frequently found in isolates from food implicated with human illness. The antagonistic property was therefore proposed in this thesis as a novel virulence factor that increases the human morbidity of the species B. cereus, in particular of the cereulide producers.

Äidinmaito - terveysjuomaa ja normaalibakteereita

The chemical composition of breast milk has been studied in detail in the past decades. Hundreds of new antibacterial and antiviral components have been found. Several molecules have been found to promote the proper function of neonatal intestine. However, microbiological studies of breast milk have been, until recently, focused mainly on detecting harmful and pathogenic bacteria and viruses. Natural microbial diversity of human milk has not been widely studied before the work reported in this thesis. This is mainly because breast milk has traditionally been thought to be sterile - even if a certain amount of commensal bacteria have usually been detected in milk samples. The first part of this licentiate thesis contains a short literature review about the anatomy and physiology of breast feeding, human milk chemical and microbiological composition, mastitis, intestinal flora and bacteriocins. The second part reports on the experiments of the licentiate work, concentrating on the microbial diversity in the milk of healthy breast-feeding mothers, and the ability of these bacteria to produce antibacterial substances against pathogenic bacteria. The results indicate that human milk is a source of commensal bacteria for infant intestine. 509 random isolates from 40 breast milk samples were isolated and identified by 16S rRNA sequencing. Median bacterial count was about 600 colony forming units per milliliter. Over half of the isolates were staphylococci, and almost one third streptococci. The most common species were skin bacteria Staphylococcus epidermidis and oral bacteria Streptococcus salivarius and Streptococcus mitis. Lactic acid bacteria, identified as members of Lactobacillus-, Lactococcus- and Leuconostoc -genera, were found in five milk samples. Enterococci were found in three samples. A novel finding in this study is the capability of these commensal bacteria to inhibit the growth of pathogens. In 90 precent of the milk samples commensal bacteria inhibiting the growth of Staphylococcus aureus were found. In 40 precent of samples the colonies could block the growth completely. One fifth of the isolated Staph. epidermidis strains, half of Str. salivarius strains, and all lactic acid bacteria and enterococci could inhibit or block the growth of Staph. aureus. In further study also Listeria innocua- and Micrococcus luteus active isolates were found in 33 and 11 precent of milk samples (out of 140). Furthermore, two Lactococcus lactis isolates from the breast milk were shown to produce bacteriocin nisin, which is an antimicrobial molecule used as a food preservative. The importance of these human milk commensal bacteria in the development of newborn intestinal flora and immune system, as well as in preventing maternal breast infections, should be further explored.

Tila tilassa : Liturgian ja tilan dialogi alttarin äärellä

This study examines the organisation and transformation of altar space in the modern Evangelical Lutheran Church of Finland in liturgical and architectural perspective. The research data consists of 65 altar spaces in The Finnish Evangelical Lutheran church buildings. All of these were characterised in Church Government records as churches , built 1962 1999 and had been consecrated. The main data was collected by means of observation, photographing, and drawing sketches of altar spaces. The focus of this study concerns the organisation of modern Finnish Evangelical Lutheran altar spaces and, in particular, their changes also in relation to the liturgical movement. The challenge of this approach was especially in discovering the spatial identity of an altar space in terms of unequivocal boundaries. The analysis was realised in three stages. Interiors, the organisation of altar space, as well as architectonic qualities of altar spaces in terms of floor elevations, shapes of ceilings, lighting, and openings in the altar space were analysed. Moreover, attention was focused on furnishing and fixed versus movable pieces of furniture (such as the altar, altar rail, the pulpit, the baptismal font, and lectern). Finally, the potential qualitative and quantitative changes in altar space were examined. All in all, the majority of churches in the data featured elongated church halls with an altar at the end of the nave. To look at the data in chronological perspective, increasingly wide church halls had been built since the 1980s (yet there was only one central hall in which the altar was placed at the middle point of the church). Every third church altar was movable. As for the focal point of this study and the altar in particular, it was my aim to pay attention to the versus populum altar and its development in relation to the (Lutheran) liturgy. Hence, it was meaningful to determine, in terms of interior design, whether liturgists were able to celebrate facing the people attending the service. In the 1960s and 70s, a versus orientem altar featured in more than half of all new Finnish Lutheran churches, yet in 2000 two out of three churches featured a versus populum altar. For architectural and esthetic reasons (and not primarily due to liturgical ideas), also altars standing freely off the walls had been constructed. In terms of the liturgy, versus populum altars had been realised in expectation of increased communication between liturgist and worshippers. However, the analysis indicated that the altar could also become a divider of space. This aspect is a novel finding in relation to earlier and concurrent discussions concerning the liturgical movement. This study concluded, all in all, that altars had been increasingly constructed closer and closer to the worshiping parish and, accordingly, used increasingly often in the versus populum manner. Lecterns were often movable until the millennium this was the case in most altar spaces. Baptismal fonts did not have a permanent place in this data, and the data even included altar spaces with no baptismal fonts in the choir, nor the church hall. The position and status of fonts was generally weakened even if baptism in the Lutheran Church was regarded as one of the two sacraments together with the eucharist. The study concluded that even if baptism is regarded as a sacrament in the church, the position and status of baptismal fonts had weakened overall in newer church architecture. In other words, the tendency of the liturgical movement to emphasise the service and its celebration had obviously had its effect on the placement of baptismal fonts in the church hall. This research indicated that the pieces of furniture that mostly involved (many kinds of) visual and spatial changes included the altar and the lectern. In certain instances, fixed furnishings had been substituted by movable pieces or, moreover, new pieces of furniture and paraphernalia such as music instruments, pieces of art, tables, chairs and plants were brought in. In the Evangelical Lutheran Church of Finland, liturgical changes were principally inspired by the Catholic Church, in which liturgical changes are essentially based on Canon Law. Unlike Finnish Lutheranism, Catholicism provides detailed rules and principles even regarding the design of an altar space. According to this study, in the Finnish Lutheran Church, the primarily functional nature of given guidelines and instructions characterises several practical solutions in furnishing.

Vedestä vai Hengestä? : Uuras Saarnivaaran kasteteologia

Of water or the Spirit? Uuras Saarnivaara s theology of baptism The aim of the study was to investigate PhD and ThD Uuras Saarnivaara s views on baptism as well as their possible changes and the reasons for them. Dr Saarnivaara said himself that he searched for the truth about the relationship between baptism and faith for decades, and had faltered in his views. The method of this research is systematic analysis. A close study of the source material shows that Dr Saarnivaara s views on baptism have most likely changed several times. Therefore, special attention was paid to the time periods defined by when his literary works were published. This resulted in revealing the different perspectives he had on baptism. The fact that Dr Saarnivaara worked on two continents Europe and North America added a challenge to the research process. At the beginning of the research, I described Dr Saarnivaara s phases of life and mapped out his vast literary production as well as presented his theological basis. Saarnivaara s theological view on the means of grace and their interrelation in the church was influenced by the Laestadian movement, which caused him to adopt the view that the Holy Spirit does not dwell in the means of grace, but in the believers. Thus the real presence of Christ in the means of grace is denied. God s word is divided into Biblical revelation and proclamation by believers through the means of grace. Also, the sacraments are overshadowed by the preached word. Because grace is received through the word of the gospel preached publicly or privately by a believer, the preacher s status gains importance at the expense of the actual means of grace. Saarnivaara was intrigued by the content of baptism from the time he was a student until the end of his life. As a young theologian, he would adopt the opinions of his teachers as well as the view of the Evangelical Lutheran Church of Finland, which at the time was dominated by the pietistic movement and the teachings of J. T. Beck. After Saarnivaara had converted to the Laestadian movement, moved to the United States and started his Luther research, he adopted a view on baptism which was to a great extent in accordance with Luther and the Lutheran Symbolical Books. Saarnivaara considered his former views on baptism unbiblical and publicly apologised for them. In the 1950s, after starting his ministry within the Finnish neopietistic movements, Saarnivaara adopted a Laestadian-neopietistic doctrine of baptism. During his Beckian-pietistic era, Saarnivaara based his baptism theology on the event of the disciples of Jesus being baptised by John the Baptist, the revival of Samaria in the Book of Acts and the conversion of Cornelius and his family, all cases where the receiving of the Holy Spirit and the baptism were two separate events in time. In order to defend the theological unity of the Bible, Saarnivaara had to interpret Jesus teachings on baptism in the Gospels and the teachings of the Apostles in the New Testament letters from a viewpoint based on the three events mentioned above. During his Beckian-pietistic era, the abovementioned basic hermeneutic choice caused Saarnivaara to separate baptism by water and baptism by the Holy Spirit in his salvation theology. Simultaneously, the faith of a small child is denied, and rebirth is divided into two parts, the objective and the subjective, the latter being moved from the moment of baptism to a possible spiritual break-through at an age when the person possesses a more mature understanding. During his Laestadian-Lutheran era, Saarnivaara s theology of baptism was biblically consistent and the same for all people regardless of the person s age. Small children receive faith in baptism through the presence of Christ. The task of other people s faith is limited to the act of bringing the child to the baptism so that the child may receive his/her own faith from Christ and be born again as a child of God. The doctrine of baptism during Saarnivaara s Laestadian-neopietistic era represents in many aspects the emphases he presented during his first era, although they were now partly more radical. Baptism offers grace; it is not a means of grace. Justification, rebirth and salvation would take place later on when a person had reached an age with a more mature understanding through the word of God. A small child cannot be born again in baptism because being born again requires personal faith, which is received through hearing and understanding the law and the gospel. Saarnivaara s views on baptism during his first and third era are, unlike during his second era, quite controversial. The question of the salvation of a small child goes unanswered, or it is even denied. The central question during both eras is the demand of conversion and personal faith at a mature age. The background for this demand is in Saarnivaara s anthropology, which accentuates man s relationship to God as an intellectual and mental matter requiring understanding, and which needs no material instruments. The two first theological eras regarding Saarnivaara s doctrine of baptism lasted around ten years. The third era lasted over 40 years until his death.

Systemic Inflammation in Preterm Infants

Even though mortality among preterm infants has decreased, their risk for chronic complications such as bronchopulmonary dysplasia (BPD) and neurological disability remains significant. One common risk factor for these is exposure to inflammation. The fetus may be exposed prenatally during maternal chorioamnionitis. Pre-eclampsia is also associated with low-grade maternal inflammation. Postnatally, local and systemic inflammation is present during respiratory distress syndrome (RDS). Furthermore, septic infections in the preterm infant are an important source of inflammatory stimuli and can lead to death in only a few hours. The diagnosis of septic infection is difficult, since reliable diagnostic markers are unavailable. This thesis evaluates peri- and postnatal systemic inflammation in preterm infants in septic infections, in RDS treated with mechanical ventilation and surfactant treatment, and in preterm infants prenatally exposed to chorioamnionitis and pre-eclampsia. Surface expressions of the activation markers CD11b, CD54, and CD62L, determined by flow cytometry on circulating phagocytes and T lymphocytes, serve as indicators of systemic inflammation. The main findings: I) In preterm infants with developing late-onset sepsis and fulminant necrotizing enterocolitis, a significant increase in CD11b expression on circulating phagocytes is already present on the day of onset of clinical symptoms. II) In preterm infants with RDS, circulating phagocytes become activated within hours after start of mechanical ventilation. In preterm infants treated for RDS with nasal continuous positive airway pressure, no such activation occurs. III) In preterm infants, RDS is associated during the first days of life with fewer circulating helper and cytotoxic T lymphocytes, of which the greater proportions are activated. Even greater proportions of circulating T cells are activated in infants subsequently developing BPD. IV) In preterm infants born after maternal pre-eclampsia, RDS-associated phagocyte CD11b up-regulation is greater than in preterm infants not exposed to pre-eclampsia during the first week of life. These findings suggest that I) an increase in CD11b expression on circulating phagocytes can identify preterm infants with late-onset sepsis as early as at sampling for blood culture and may thus aid in the diagnosis. II) In preterm infants with RDS, initiation of mechanical ventilation, but not the use of nasal continuous positive airway pressure, promotes a systemic inflammatory reaction; exogenous surfactant does not seem to promote inflammation. III) In addition to activation of circulating cells of the innate immunity in preterm infants with RDS, the circulating cells of the adaptive immunity are activated. The activation of adaptive immunity may link acute inflammation and development of chronic inflammation-associated problems such as BPD. IV) Maternal pre-eclampsia may prime neonatal immunity to react more strongly to postnatal stimuli. In conclusion, the preterm infant is exposed to numerous potentially injurious events such as intrauterine inflammation, respiratory distress syndrome (RDS), and systemic infections, all evoking systemic inflammation. Due to ongoing development of the lung and the brain, this may, in addition to acute injury, lead to aberrant lung and brain development and to clinical syndromes of BPD and neurologic sequelae.

Early life determinants of atopy : A 20-year prospective follow-up study on unselected, healthy newborns

Atopy-related allergic diseases, i.e. allergic rhinoconjunctivitis, atopic dermatitis and asthma, have increased in frequency in the industrialized countries. In order to reverse this trend, effective preventive strategies need to be developed. This requires a better understanding of the early-life events leading to the expression of the atopic phenotype. The present study has aimed at defining early-life factors and markers associated with the subsequent development of allergic diseases in a cohort of 200 healthy, unselected Finnish newborns prospectively followed up from birth to age 20 years. Their mothers were encouraged to start and maintain exclusive breastfeeding as long as it was nutritionally sufficient for the infant. Consequently, all the infants received some duration of exclusive breastfeeding, 58% of the infants were on exclusive breastfeeding for the first 6 months of life, and 18% received this feeding at least for the first 9 months. Of the infants, 42% had a family history of allergy. After the first year of follow-up, the children were re-assessed at ages 5, 11 and 20 years with clinical examination, skin prick testing, and parental and personal interviews. Exclusive breastfeeding for over 9 months was associated with atopic dermatitis and symptoms of food hypersensitivity at age 5 years, and with symptoms of food hypersensitivity at age 11 years in the children with a familial allergy. Subjects with allergic symptoms or a positive skin prick test in childhood or adolescence had lower retinol concentrations during their infancy and childhood than others. An elevated cord serum immunoglobulin E concentration predicted subsequent atopic manifestations though with modest sensitivity. Children and adolescents with allergic symptoms, skin prick test positivity and an elevated IgE had lower total cholesterol levels in infancy and childhood than the nonatopic subjects. In conclusion, prolonging strictly exclusive breastfeeding for over 9 months of age was not of help in prevention of allergic symptoms; instead, it was associated with increased atopic dermatitis and food hypersensitivity symptoms in childhood. Due to the modest sensitivity, cord serum IgE is not an effective screening method for atopic predisposition in the general population. Retinol and cholesterol concentrations in infancy were inversely associated with the subsequent development of allergic symptoms. Based on these findings, it is proposed that there may be differences in the inborn regulation of retinol and cholesterol levels in children with and without a genetic susceptibility to atopy, and these may play a role in the development of atopic sensitization and allergic diseases.