Ancient Philosophers on Mental Illness

This dissertation is about ancient philosophers notions of mental illness, from Plato onwards. Mental illness here means disorders that, in ancient medical thought, were believed to originate in the body but to manifest themselves predominantly through mental symptoms. These illnesses were treated by physical means, which were believed to address the bodily cause of the illness, conceived of as an elemental imbalance or a state of cephalic stricture , for example. Sometimes the mental symptoms were addressed directly by psychotherapeutic means. The first and most important question explored concerns how the ancient philosophers responded to the medical notion of mental illness, and how they explained such illnesses in their theories of physiology and psychology. Although the illnesses are seldom discussed extensively, the philosophers were well aware of their existence and regarded their occurrence an indication of the soul s close dependence on the body. This called for a philosophical account. The second question addressed has to do with the ancient philosophers role as experts in mental problems of a non-medical kind, such as unwanted emotions. These problems were dubbed diseases of the soul , and the philosophers thus claimed to be doctors of the soul. Although the distinction between mental illnesses and diseases of the soul was often presented as rather obvious, there was some vagueness and overlap. There is still a third question that is explored, concerning the status of both mental illnesses and diseases of the soul as unnatural conditions, the role of the human body in the philosophical aetiologies of evil, and the medico-philosophical theories of psycho-physiological temperaments. This work consists of an introduction and five main chapters, focusing on Plato, Aristotle, the Stoics and Galen, and the Sceptics, the Epicureans and later Platonists. The sources drawn on are the original Greek and Latin philosophical and medical texts. It appears that the philosophers accepted the medical notion of mental illness, but interpreted it in various ways. The differences in interpretation were mostly attributable to differences in their theories of the soul. Although the distinction between mental illness and diseases of the soul was important, marking the boundary between the fields of expertise of medicine and philosophy, and of the individual s moral responsibilities, the problematic aspects of establishing it are discussed rather little in ancient philosophy. There may have been various reasons for this. The medical descriptions of mental illness are often extreme, symptoms of the psychotic type excluding the possibility of the condition being of the non-medical kind. In addition, the rigid normativeness of ancient philosophical anthropologies and their rigorous notion of human happiness decreased the need to assess the acceptability of individual variation in their emotional and intellectual lives and external behaviour.

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.

"Secoituxesta järjettömäin luondocappalden canssa" : Perversiot, oikeuselämä ja kansankulttuuri 1700-luvun Suomessa

Bestiality was in the 18th century a more difficult problem in terms of criminal policy in Sweden and Finland than in any other Christian country in any other period. In the legal history of deviant sexuality, the phenomenon was uniquely widespread by international comparison. The number of court cases per capita in Finland was even higher than in Sweden. The authorities classified bestiality among the most serious crimes and a deadly sin. The Court of Appeal in Turku opted for an independent line and was clearly more lenient than Swedish courts of justice. Death sentences on grounds of bestiality ended in the 1730s, decades earlier than in Sweden. The sources for the present dissertation include judgment books and Court of Appeal decisions in 253 cases, which show that the persecution of those engaging in bestial acts in 18th century Finland was not organised by the centralised power of Stockholm. There is little evidence of local campaigns that would have been led by authorities. The church in its orthodoxy was losing ground and the clergy governed their parishes with more pragmatism than the Old Testament sanctioned. When exposing bestiality, the legal system was compelled to rely on the initiative of the public. In cases of illicit intercourse or adultery the authorities were even more dependent on the activeness of the local community. Bestiality left no tangible evidence, illegitimate children, to betray the crime to the clergy or secular authorities. The moral views of the church and the local community were not on a collision course. It was a common view that bestiality was a heinous act. Yet nowhere near all crimes came to the authorities' knowledge. Because of the heavy burden of proof, the legal position of the informer was difficult. Passiveness in reporting the crime was partly because most Finns felt it was not their place to intervene in their neighbours' private lives, as long as that privacy posed no serious threat to the neighbourhood. Hidden crime was at least as common as crime more easily exposed and proven. A typical Finnish perpetrator of bestiality was a young unmarried man with no criminal background or mental illness. The suspects were not members of ethnic minorities or marginal social groups. In trials, farmhands were more likely to be sentenced than their masters, but a more salient common denominator than social and economical status was the suspects' young age. For most of the defendants bestiality was a deep-rooted habit, which had been adopted in early youth. This form of subculture spread among the youth, and the most susceptible to experiment with the act were shepherds. The difference between man and animal was not clear-cut or self-evident. The difficulty in drawing the line is evident both in legal sources and Finnish folklore. The law that required that the animal partners be slaughtered led to the killing of thousands of cows and mares, and thereby to substantial material losses to their owners. Regarding bestiality as a crime against property motivated people to report it. The belief that the act would produce human-animal mongrels or that it would poison the milk and the meat horrified the public more than the teachings of the church ever could. Among the most significant aspects in the problems regarding the animals is how profoundly different the worldview of 18th century people was from that of today.

Pain in juvenile idiopathic arthritis : parents and children as agents of disease management

Juvenile idiopathic arthritis (JIA) is a severe childhood disease usually characterized by long-term morbidity, unpredictable course, pain, and limitations in daily activities and social participation. The disease affects not only the child but also the whole family. The family is expected to adhere to an often very laborious regimen over a long period of time. However, the parental role is incoherently conceptualized in the research field. Pain in JIA is of somatic origin, but psychosocial factors, such as mood and self-efficacy, are critical in the perception of pain and in its impact on functioning. This study examined the factors correlating and possibly explaining pain in JIA, with a special emphasis on the mutual relations between parent- and patient-driven variables. In this patient series pain was not associated with the disease activity. The degree of pain was on average fairly low in children with JIA. When the children were clustered according to age, anxiety and depression, four distinguishable cluster groups significantly associated with pain emerged. One of the groups was described by concept vulnerability because of unfavorable variable associations. Parental depressive and anxiety symptoms accompanied by illness management had a predictive power in discriminating groups of children with varying distress levels. The parent’s and child’s perception of a child’s functional capability, distress, and somatic self-efficacy had independent explanatory power predicting the child’s pain. Of special interest in the current study was self-efficacy, which refers to the belief of an individual that he/she has the ability to engage in the behavior required for tackling the disease. In children with JIA, strong self-efficacy was related to lower levels of pain, depressive symptoms and trait anxiety. This suggests strengthening a child’s sense of self-efficacy, when helping the child to cope with his or her disease. Pain experienced by a child with JIA needs to be viewed in a multidimensional bio-psycho-social context that covers biological, environmental and cognitive behavioral mechanisms. The relations between the parent-child variables are complex and affect pain both directly and indirectly. Developing pain-treatment modalities that recognize the family as a system is also warranted.

Psychological consequences of cancer from the salutogenic and dyadic perspective

Previous empirical research has shown that positive, i.e. salutogenic, psychological resources and social support, have health-promoting effects in stressful life situations. In the present study the associations between sense of coherence (SOC), dispositional optimism, partner support, psychological distress, and quality of life among cancer patients and their partners were examined. The data was collected from Helsinki University Central Hospital in 1997 2000 by self-report questionnaires approximately 2, 8, and 14 months post diagnosis. Participants in studies I-IV were 155, 123, 153, and 147 cancer patients and their partners, respectively. The sample of the present study consisted of physically relatively well-functioning patients, whose overall psychological wellbeing was generally good as compared to the healthy population. Partners in this study, however, reacted more strongly to their partners illness and treatment. The partners displayed e.g. higher levels of anxiety and depression than the patients. The results of this study indicated that cancer patients and their partners with strong SOC and who are optimistic report fewer symptoms of distress. Moreover, patients who display an optimistic attitude to life, who receive support from their partner, and who control how they express anger have a better quality of life. The findings also confirmed that the role of the partner is significant in coping with cancer. The symptoms of depression and anxiety in patients and partners were associated, and the partner s optimism seemed to protect also the patient from elevated levels of anxiety. The role of the partner was also highlighted in the couples anger-expression styles. The patients and partners tendency to inhibit anger was associated with decreased partner support and worse patient quality of life. Finally, in the present study we found substantial gender differences. For the patients, partner support was more significant for the women than for the men. Furthermore, for the female patients, the husband s tendency to openly express anger (anger-out) had a negative impact on their psychological quality of life, whereas the wives high anger-out seemed to predict good psychological quality of life in the men. Also, in this study the female partners reported higher levels of anxiety and depression as compared to the male partners. The results of the present study extend the previous literature on positive psychological resources and psychological wellbeing among cancer couples. Furthermore, these findings support the theory on SOC and optimism as health-promoting factors. However, the construct of SOC seems to include other important elements besides optimism. The findings of this study are applicable in designing new rehabilitation programmes for cancer patients and their partners.

Finnish Homicides and Mental Disorders: An investigation of offense and offender characteristics

Although the majority of people with mental illness are not violent, scientific studies over the last decades show that certain psychiatric disorders increase the risk of violent behavior, including homicide. This thesis examined crime scene behaviors and offender background characteristics among mentally ill Finnish homicide offenders. Previously, homicide crime scene behaviors have been investigated in relation to offender demographic characteristics, whereas this study compares the behaviors of offenders with various mental illnesses. The study design was a retrospective chart review of the forensic psychiatric statements of Finnish homicide offenders. The work consists of four substudies. The aims of the study were as follows: To describe differences in the childhood and family backgrounds as well as in the adolescent and adult adjustment of Finnish homicide offenders belonging to different diagnostic categories (schizophrenia, personality disorder, alcoholism, drug addiction or no diagnosis). Further, the study examined associations between the crime scene behaviors and mental status of these offenders. Also, the distinguishing characteristics between two groups of offenders with schizophrenia were examined: early starters, who present antisocial behavior before the onset of schizophrenia, and late starters, who first offend after the onset of mental disorder. Finally, it was investigated how the use of excessive violence is associated with clinical and circumstantial variables as well as offender background characteristics among homicide offenders with schizophrenia. The main findings of the study can be summarized as follows. First, offenders with personality disorder or drug addiction had experienced multiple difficulties in their early environments: both family and individual problems were typical. Offenders with schizophrenia were relatively well-adjusted in childhood compared to the other groups. However, in adolescence and adulthood, social isolation, withdrawal and other difficulties attributable to these offenders illness became evident. In several aspects, offenders with alcohol dependency resembled offenders with no diagnosis in that these offenders had less problematic backgrounds compared to other groups. Second, the results showed that crime scene behaviors, victim gender and the victim-offender relationship differ between the groups. In particular, offenders with a diagnosis of schizophrenia or drug addiction have some unique features in their crime scene behaviors and choice of victims. Offenders with schizophrenia were more likely to kill a blood relative, to use a sharp weapon and to injure the victim s face. Drug addiction was associated with stealing from the victim and trying to cover up the body. Third, the results suggest that the offense characteristics of early- and late-start offenders with schizophrenia differ only modestly. However, several significant differences between the groups were found in characteristics of offenders: early starters had experienced a multitude of problems in their childhood surroundings and also later in life. Fourth, violent acts where the offender did not commit the offense alone or had previous homicidal history were predictive of excessive violence among offenders with schizophrenia. Positive psychotic symptoms did not predict the use of excessive violence. Nearly one third of the cases in the sample involved multiple and severe violence, including features such as sadism, mutilation, sexual components or extreme stabbing. In sum, mentally disordered homicide offenders are heterogeneous in their offense characteristics as well as their background characteristics. Empirically based information on how the offender s mental state is associated with specific crime scene behaviors can be utilized within the police force in developing methods of prioritizing suspects in unsolved homicide cases. Also, these results emphasise the importance of early interventions for problem families and children at risk of antisocial behavior. They may also contribute to the development of effective treatment for violent offenders.

Evaluation of driving ability of the disabled persons in the context of the psychological activity theory

In the future the number of the disabled drivers requiring a special evaluation of their driving ability will increase due to the ageing population, as well as the progress of adaptive technology. This places pressure on the development of the driving evaluation system. Despite quite intensive research there is still no consensus concerning what is the factual situation in a driver evaluation (methodology), which measures should be included in an evaluation (methods), and how an evaluation has to be carried out (practise). In order to find answers to these questions we carried out empirical studies, and simultaneously elaborated upon a conceptual model for driving and a driving evaluation. The findings of empirical studies can be condensed into the following points: 1) A driving ability defined by the on-road driving test is associated with different laboratory measures depending on the study groups. Faults in the laboratory tests predicted faults in the on-road driving test in the novice group, whereas slowness in the laboratory predicted driving faults in the experienced drivers group. 2) The Parkinson study clearly showed that even an experienced clinician cannot reliably accomplish an evaluation of a disabled person’s driving ability without collaboration with other specialists. 3) The main finding of the stroke study was that the use of a multidisciplinary team as a source of information harmonises the specialists’ evaluations. 4) The patient studies demonstrated that the disabled persons themselves, as well as their spouses, are as a rule not reliable evaluators. 5) From the safety point of view, perceptible operations with the control devices are not crucial, but correct mental actions which the driver carries out with the help of the control devices are of greatest importance. 6) Personality factors including higher-order needs and motives, attitudes and a degree of self-awareness, particularly a sense of illness, are decisive when evaluating a disabled person’s driving ability. Personality is also the main source of resources concerning compensations for lower-order physical deficiencies and restrictions. From work with the conceptual model we drew the following methodological conclusions: First, the driver has to be considered as a holistic subject of the activity, as a multilevel hierarchically organised system of an organism, a temperament, an individuality, and a personality where the personality is the leading subsystem from the standpoint of safety. Second, driving as a human form of a sociopractical activity, is also a hierarchically organised dynamic system. Third, in an evaluation of driving ability it is a question of matching these two hierarchically organised structures: a subject of an activity and a proper activity. Fourth, an evaluation has to be person centred but not disease-, function- or method centred. On the basis of our study a multidisciplinary team (practitioner, driving school teacher, psychologist, occupational therapist) is recommended for use in demanding driver evaluations. Primary in a driver’s evaluations is a coherent conceptual model while concrete methods of evaluations may vary. However, the on-road test must always be performed if possible.

Social-class inequalities in ill health - the contribution of physical workload

Tutkimuksen aiheita olivat yhteiskuntaluokkien väliset erot sairastavuudessa ja alentuneessa toimintakyvyssä, sekä fyysisen työkuormituksen ja joidenkin muiden työolojen vaikutus sairastavuuteen. Empiirisestä työstä on raportoitu myös neljässä kansainvälisissä tieteellisissä aikakauskirjoissa julkaistussa artikkelissa. Tässä julkaistu yhteenveto sisältää tulosten yhteenvedon lisäksi myös tutkimusta koskevien käsitteellisten ja teoreettisten kysymysten sekä tutkimustradition kriittisen katsauksen. Työn päätavoitteita olivat 1) tutkia fyysisesti kuormittavan työn, ja jossain määrin muiden työolojen osuutta yhteiskuntaluokkien välisiin eroihin sairaudessa ja toimintakyvyn alentuneisuudessa; 2) tutkia työn fyysisen kuormittavuuden, työhön liittyvien vaikutusmahdollisuuksien ja hallinnan (decision latitude), luokka-aseman, iän ja sukupuolen yhteisvaikutuksia heikentyneeseen terveydentilaan; sekä 3) tutkia missä määrin mekaanisten työaltisteiden ja tuki- ja liikuntaelinsairastavuuden välinen yhteys voi selittää yhteiskuntaluokkien välisiä eroja heikentyneessä yleisessä terveydentilassa. Tutkittavat olivat keski-ikäisiä Helsingin kaupungin työntekijöitä. Analyysit perustuivat poikittaisasetelmaan, ja käytetty aineisto oli Helsinki Health Studyn vuosien 2000 ja 2002 välillä kerättyä aineistoa. Analyyseihin käytetyssä aineistossa oli 3740:stä 8002:een tutkittavaa. Tulosten perusteella fyysisillä (sekä fysikaalisilla) työoloilla on merkittävä vaikutus yhteiskuntaluokkien välisiin eroihin yleisessä sairastavuudessa, toimintakyvyn heikentymisessä, tuki- ja liikuntaelinsairastavuudessa sekä itsearvioidussa terveydentilassa. Naisilla lähes puolet heikentyneen toimintakyvyn ja koetun terveydentilan luokkaeroista vaikutti olevan selitettävissä fyysisellä työkuormituksella. Hallintamahdollisuuksien ei havaittu merkittävästi muuttavan fyysisen kuormituksen vaikutusta toimintakykyyn. Fyysisen kuormittavuuden terveysvaikutus voimistui kasvavan iän mukaan enemmän naisilla kuin miehillä. Osa, mutta ei koko fyysisen kuormituksen vaikutus yhteiskuntaluokkien eroihin heikentyneessä terveydessä vaikutti välittyvän tuki- ja liikuntaelinsairastavuuden kautta. Terveys ja sairaus eivät ole yhtenäisiä tiloja, ja siksi monet eri sosiaalisesti ja rakenteellisesti määräytyvät olosuhteet todennäköisesti vaikuttavat yhteiskunnallisten terveyserojen syntymiseen. Fyysis-materiaalisten olojen vaikutusta terveyserojen syntyyn nyky-yhteiskunnassa on mahdollisesti aliarvioitu. Yhteiskuntaluokkien väliset erot fyysis-materiaalisissa olosuhteissa eivät ole kadonneet, ja nämä erot todennäköisesti vaikuttavat terveyserojen syntyyn.

Cancer survivors at work : Work-related problems and factors associated with their employment, work ability and social support from the work community

Due to the improved prognosis of many forms of cancer, an increasing number of cancer survivors are willing to return to work after their treatment. It is generally believed, however, that people with cancer are either unemployed, stay at home, or retire more often than people without cancer. This study investigated the problems that cancer survivors experience on the labour market, as well as the disease-related, sociodemographic and psychosocial factors at work that are associated with the employment and work ability of cancer survivors. The impact of cancer on employment was studied combining the data of Finnish Cancer Registry and census data of the years 1985, 1990, 1995 or 1997 of Statistics Finland. There were two data sets containing 46 312 and 12 542 people with cancer. The results showed that cancer survivors were slightly less often employed than their referents. Two to three years after the diagnosis the employment rate of the cancer survivors was 9% lower than that of their referents (64% vs. 73%), whereas the employment rate was the same before the diagnosis (78%). The employment rate varied greatly according to the cancer type and education. The probability of being employed was greater in the lower than in the higher educational groups. People with cancer were less often employed than people without cancer mainly because of their higher retirement rate (34% vs. 27%). As well as employment, retirement varied by cancer type. The risk of retirement was twofold for people having cancer of the nervous system or people with leukaemia compared to their referents, whereas people with skin cancer, for example, did not have an increased risk of retirement. The aim of the questionnaire study was to investigate whether the work ability of cancer survivors differs from that of people without cancer and whether cancer had impaired their work ability. There were 591 cancer survivors and 757 referents in the data. Even though current work ability of cancer survivors did not differ between the survivors and their referents, 26% of cancer survivors reported that their physical work ability, and 19% that their mental work ability had deteriorated due to cancer. The survivors who had other diseases or had had chemotherapy, most often reported impaired work ability, whereas survivors with a strong commitment to their work organization, or a good social climate at work, reported impairment less frequently. The aim of the other questionnaire study containing 640 people with the history of cancer was to examine extent of social support that cancer survivors needed, and had received from their work community. The cancer survivors had received most support from their co-workers, and they hoped for more support especially from the occupational health care personnel (39% of women and 29% of men). More support was especially needed by men who had lymphoma, had received chemotherapy or had a low education level. The results of this study show that the majority of the survivors are able to return to work. There is, however, a group of cancer survivors who leave work life early, have impaired work ability due to their illness, and suffer from lack of support from their work place and the occupational health services. Treatment-related, as well as sociodemographic factors play an important role in survivors' work-related problems, and presumably their possibilities to continue working.

Campylobacter Infections of Domestic Origin in Finland

Campylobacter jejuni and C. coli are the leading causes of human bacterial gastroenteritis in developed countries. Most human Campylobacter infections are sporadic and a seasonal peak in the distribution of infections can be seen in the summer months in several countries, including Finland. A variety of risk factors for Campylobacter infections have been identified; handling and eating poultry, drinking unpasteurized milk, contact with domestic animals, and travelling abroad. However, the relative importance of the different risk factors in sporadic cases of Campylobacter infection remains unknown. In most cases, the infection is self-limiting and no specific treatment is required. Campylobacter enteritis can cause a wide range of complications, including reactive arthritis (ReA) that is reported in 1-5% of the cases. Seven clinical microbiology laboratories serving different geographical areas of Finland, participated in this multi-centre study, conducted during a seasonal peak in 2002. In a matched case-control study, domestically-acquired sporadic Campylobacter infections from three geographical areas were collected. The final study comprised 100 cases and 137 controls. Risk factors for sporadic domestically-acquired Campylobacter infections were identified on the basis of a questionnaire; swimming in natural waters was found to be a novel risk factor for Campylobacter infection. Other independent risk factors were tasting or eating raw or undercooked meat and drinking untreated water from a dug well. The role of bacterial strain and host characteristics are not fully understood in Campylobacter infections. Exposure factors, demographical characteristics, and the serotype of the Campylobacter isolate may affect the severity of the enteritis. This cross-sectional study comprised 114 patients with C. jejuni enteritis, diagnosed in three clinical microbiology laboratories; most of the patients had participated in the previous case-control study. Swimming was associated with age ≤ 5 years and serotype Pen 6,7 was found significantly more often among patients reporting swimming. The geographical distribution among serotypes varied; serotype Pen 4-complex appeared more often in patients from urban areas and serotype Pen 21 among patients from more rural areas. Thus, risk factors and sources of infection for C. jejuni infection may vary among individuals depending on age and geographical location. The in vitro susceptibilities of C. jejuni and C. coli strains isolated from patients infected abroad (85 strains) or domestically (393 strains) revealed that susceptibility to erythromycin is still high, even among isolates of foreign origin. However, the novel antimicrobial agent telithromycin did not offer any advantage over erythromycin; isolates with high minimal inhibitory concentrations (MICs) for erythromycin also showed reduced susceptibility to telithromycin. Reduced susceptibility to fluoroquinolones was detected almost exclusively among isolates of foreign origin and half of these isolates with high MICs for fluoroquinolones also showed elevated MICs for doxycycline. Questionnaires concerning complications associated with C. jejuni enteritis were sent to patients two months after becoming ill; 201 patients from seven different geographical areas were included in the study. Musculoskeletal complications after C. jejuni infection were commonly reported by patients (39%). The incidence of classical ReA was 4% and that of Achilles enthesopathy and/or heel pain 9%. Other C. jejuni-associated reactive joint symptoms were commonly reported, however, due to their milder nature seldom seen and diagnosed by a physician. The severity of the enteritis may predict further complications; stomach ache during enteritis was connected to the development of later joint pain. Early antimicrobial treatment, within two days from the start of symptoms, shortened the duration of diarrhoea by two days but did not prevent later musculoskeletal complications. Campylobacter is an important human enteropathogen and causes a significant burden of illness. As the incidence of Campylobacter infections is high, the importance of the infection and the occurrence of complications will increase. This stresses the importance of understanding the risk factors for acquiring Campylobacter infection and how bacterial strain and host characteristics may affect the risk for infection. The role of antimicrobial treatment for acute Campylobacter enteritis seems to be marginal and should be used restrictively.

Sindbis virus and Pogosta disease in Finland

Sindbis virus (SINV) (genus Alphavirus, family Togaviridae) is an enveloped virus with a genome of single-stranded, positive-polarity RNA of 11.7 kilobases. SINV is widespread in Eurasia, Africa, and Australia, but clinical infection only occurs in a few geographically restricted areas, mainly in Northern Europe. In Europe, antibodies to SINV were detected from patients with fever, rash, and arthritis for the first time in the early 1980s in Finland. It became evident that the causative agent of this syndrome, named Pogosta disease, was closely related to SINV. The disease is also found in Sweden (Ockelbo disease) and in Russia (Karelian fever). Since 1974, for unknown reason, the disease has occurred as large outbreaks every seven years in Finland. This study is to a large degree based on the material collected during the 2002 Pogosta disease outbreak in Finland. We first developed SINV IgM and IgG enzyme immunoassays (EIA), based on highly purified SINV, to be used in serodiagnostics. The EIAs correlated well with the hemagglutination inhibition (HI) test, and all individuals showed neutralizing antibodies. The sensitivities of the IgM and IgG EIAs were 97.6% and 100%, and specificities 95.2% and 97.6%, respectively. E1 and E2 envelope glycoproteins of SINV were shown to be recognized by IgM and IgG in the immunoblot early in infection. We isolated SINV from five patients with acute Pogosta disease; one virus strain was recovered from whole blood, and four other strains from skin lesions. The etiology of Pogosta disease was confirmed by these first Finnish SINV strains, also representing the first human SINV isolates from Europe. Phylogenetic analysis indicated that the Finnish SINV strains clustered with the strains previously isolated from mosquitoes in Sweden and Russia, and seemed to have a common ancestor with South-African strains. Northern European SINV strains could be maintained locally in disease-endemic regions, but the phylogenetic analysis also suggests that redistribution of SINV tends to occur in a longitudinal direction, possibly with migratory birds. We searched for SINV antibodies in resident grouse (N=621), whose population crashes have previously coincided with human SINV outbreaks, and in migratory birds (N=836). SINV HI antibodies were found for the first time in birds during their spring migration to Northern Europe, from three individuals: red-backed shrike, robin, and song thrush. Of the grouse, 27.4% were seropositive in 2003, one year after a human outbreak, but only 1.4% of the grouse were seropositive in 2004. Thus, grouse might contribute to the human epidemiology of SINV. A total of 86 patients with verified SINV infection were recruited to the study in 2002. SINV RNA detection or virus isolation from blood and/or skin lesions was successful in eight patients. IgM antibodies became detectable within the first eight days of illness, and IgG within 11 days. The acute phase of Pogosta disease was characterized by arthritis, itching rash, fatigue, mild fever, headache, and muscle pain. Half of the patients reported in self-administered questionnaires joint symptoms to last > 12 months. Physical examination in 49 of these patients three years after infection revealed persistent joint manifestations. Arthritis (swelling and tenderness in physical examination) was diagnosed in 4.1% (2/49) of the patients. Tenderness in palpation or in movement of a joint was found in 14.3% of the patients in the rheumatologic examination, and additional 10.2% complained persisting arthralgia at the interview. Thus, 24.5% of the patients had joint manifestations attributable to the infection three years earlier. A positive IgM antibody response persisted in 3/49 of the patients; both two patients with arthritis were in this group. Persistent symptoms of SINV infection might have considerable public health implications in areas with high seroprevalence. The age-standardized seroprevalence of SINV (1999-2003, N=2529) in the human population in Finland was 5.2%. The seroprevalence was high in North Karelia, Kainuu, and Central Ostrobothnia. The incidence was highest in North Karelia. Seroprevalence in men (6.0%) was significantly higher than in women (4.1%), however, the average annualized incidence in the non-epidemic years was higher in women than in men, possibly indicating that infected men are more frequently asymptomatic. The seroprevalence increased with age, reaching 15.4% in persons aged 60-69 years. The incidence was highest in persons aged 50-59 years.

Markers of systemic inflammation in diagnostics and in prediction of outcome of community-acquired infection

Sepsis is associated with a systemic inflammatory response. It is characterised by an early proinflammatory response and followed by a state of immunosuppression. In order to improve the outcome of patients with infection and sepsis, novel therapies that influence the systemic inflammatory response are being developed and utilised. Thus, an accurate and early diagnosis of infection and evaluation of immune state are crucial. In this thesis, various markers of systemic inflammation were studied with respect to enhancing the diagnostics of infection and of predicting outcome in patients with suspected community-acquired infection. A total of 1092 acutely ill patients admitted to a university hospital medical emergency department were evaluated, and 531 patients with a suspicion of community-acquired infection were included for the analysis. Markers of systemic inflammation were determined from a blood sample obtained simultaneously with a blood culture sample on admission to hospital. Levels of phagocyte CD11b/CD18 and CD14 expression were measured by whole blood flow cytometry. Concentrations of soluble CD14, interleukin (IL)-8, and soluble IL-2 receptor α (sIL-2Rα) were determined by ELISA, those of sIL-2R, IL-6, and IL-8 by a chemiluminescent immunoassay, that of procalcitonin by immunoluminometric assay, and that of C-reactive protein by immunoturbidimetric assay. Clinical data were collected retrospectively from the medical records. No marker of systemic inflammation, neither CRP, PCT, IL-6, IL-8, nor sIL-2R predicted bacteraemia better than did the clinical signs of infection, i.e., the presence of infectious focus or fever or both. IL-6 and PCT had the highest positive likelihood ratios to identify patients with hidden community-acquired infection. However, the use of a single marker failed to detect all patients with infection. A combination of markers including a fast-responding reactant (CD11b expression), a later-peaking reactant (CRP), and a reactant originating from inflamed tissues (IL-8) detected all patients with infection. The majority of patients (86.5%) with possible but not verified infection showed levels exceeding at least one cut-off limit of combination, supporting the view that infection was the cause of their acute illness. The 28-day mortality of patients with community-acquired infection was low (3.4%). On admission to hospital, the low expression of cell-associated lipopolysaccharide receptor CD14 (mCD14) was predictive for 28-day mortality. In the patients with severe forms of community-acquired infection, namely pneumonia and sepsis, high levels of soluble CD14 alone did not predict mortality, but a high sCD14 level measured simultaneously with a low mCD14 raised the possibility of poor prognosis. In conclusion, to further enhance the diagnostics of hidden community-acquired infection, a combination of inflammatory markers is useful; 28-day mortality is associated with low levels of mCD14 expression at an early phase of the disease.

Cereulide producing B. cereus and amylosin producing B. subtilis and B. mojavensis : characterization of strains and toxigenicities

B. cereus is one of the most frequent occurring bacteria in foods . It produces several heat-labile enterotoxins and one stable non-protein toxin, cereulide (emetic), which may be pre-formed in food. Cereulide is a heat stable peptide whose structure and mechanism of action were in the past decade elucidated. Until this work, the detection of cereulide was done by biological assays. With my mentors, I developed the first quantitative chemical assay for cereulide. The assay is based on liquid chromatography (HPLC) combined with ion trap mass spectrometry and the calibration is done with valinomycin and purified cereulide. To detect and quantitate valinomycin and cereulide, their [NH4+] adducts, m/z 1128.9 and m/z 1171 respectively, were used. This was a breakthrough in the cereulide research and became a very powerful tool of investigation. This tool made it possible to prove for the first time that the toxin produced by B. cereus in heat-treated food caused human illness. Until this thesis work (Paper II), cereulide producing B. cereus strains were believed to represent a homogenous group of clonal strains. The cereulide producing strains investigated in those studies originated mostly from food poisoning incidents. We used strains of many origins and analyzed them using a polyphasic approach. We found that the cereulide producing B. cereus strains are genetically and biologically more diverse than assumed in earlier studies. The strains diverge in the adenylate kinase (adk) gene (two sequence types), in ribopatterns obtained with EcoRI and PvuII (three patterns), tyrosin decomposition, haemolysis and lecithine hydrolysis (two phenotypes). Our study was the first demonstration of diversity within the cereulide producing strains of B. cereus. To manage the risk for cereulide production in food, understanding is needed on factors that may upregulate cereulide production in a given food matrix and the environmental factors affecting it. As a contribution towards this direction, we adjusted the growth environment and measured the cereulide production by strains selected for diversity. The temperature range where cereulide is produced was narrower than that for growth for most of the producer strains. Most cereulide was by most strains produced at room temperature (20 - 23ºC). Exceptions to this were two faecal isolates which produced the same amount of cereulide from 23 ºC up until 39ºC. We also found that at 37º C the choice of growth media for cereulide production differed from that at the room temperature. The food composition and temperature may thus be a key for understanding cereulide production in foods as well as in the gut. We investigated the contents of [K+], [Na+] and amino acids of six growth media. Statistical evaluation indicated a significant positive correlation between the ratio [K+]:[Na+] and the production of cereulide, but only when the concentrations of glycine and [Na+] were constant. Of the amino acids only glycine correlated positively with high cereulide production. Glycine is used worldwide as food additive (E 640), flavor modifier, humectant, acidity regulator, and is permitted in the European Union countries, with no regulatory quantitative limitation, in most types of foods. B. subtilis group members are endospore-forming bacteria ubiquitous in the environment, similar to B. cereus in this respect. Bacillus species other than B. cereus have only sporadically been identified as causative agents of food-borne illnesses. We found (Paper IV) that food-borne isolates of B. subtilis and B. mojavensis produced amylosin. It is possible that amylosin was the agent responsible for the food-borne illness, since no other toxic substance was found in the strains. This is the first report on amylosin production by strains isolated from food. We found that the temperature requirement for amylosin production was higher for the B. subtilis strain F 2564/96, a mesophilic producer, than for B. mojavensis strains eela 2293 and B 31, psychrotolerant producers. We also found that an atmosphere with low oxygen did not prevent the production of amylosin. Ready-to-eat foods packaged in micro-aerophilic atmosphere and/or stored at temperatures above 10 °C, may thus pose a risk when toxigenic strains of B. subtilis or B. mojavensis are present.

Psykoottisen mielenterveyspotilaan uskonnonvapaus

Tämän tutkimuksen tarkoituksena on selvittää psykoottisen mielenterveyspotilaan uskonnonvapautta. Tutkimuskysymyksiä on kolme: Millä perusteilla psykoottisen potilaan uskonnonvapaus on turvattu ja millä perusteilla sitä rajoitetaan? Miten psykoottinen ja uskonnollinen todellisuudentulkinta eroavat toisistaan? Vaarantaako psykiatriseen todellisuudentulkintaan perustuva hoito potilaan negatiivisen uskonnonvapauden eli oikeuden elää ilman uskontoa? Tutkimusmetodina on systemaattinen analyysi. Lähteet ovat perustusoikeudet, mielenterveyslaki, potilaslaki, YK:n Principles for the protection of persons with mental illness and the improvement of mental health care, Maailman psykiatriyhdistyksen Madridin julistus ja Suomen mielenterveysseuran Mielenterveyspotilaan oikeudet. Uskonnonvapautta tarkastellaan tässä tutkimuksessa kahden eri vapauskäsityksen näkökulmasta: ulkoisena vapautena, joka edellyttää kompetenssia ja autenttisuutta, sekä ulkoisen ja sisäisen vapauden summana, johon kompetenssi ja autenttisuus sisältyvät. Psykoottisella potilaalla on ihmisyytensä ja kansalaisuutensa perusteella lähtökohtaisesti täysi uskonnonvapaus, mutta sitä voidaan rajoittaa. Jos uskonnonvapaus ymmärretään ulkoiseksi vapaudeksi, rajoittaa psykoottisen potilaan uskonnonvapautta tahdosta riippumattomassa hoidossa hänen terveytensä ja turvallisuutensa suojaaminen. Uskonnonvapauden rajoittaminen voidaan perustella sillä, ettei psykoottinen potilas täytä uskonnonvapauden edellytyksiä eli kompetenssia ja autenttisuutta, sillä, että potilaan terveyteen ja turvallisuuteen liittyvät oikeudet priorisoidaan uskonnonvapauden yläpuolelle sekä sillä, että pyritään terveyshyötyyn. Jos uskonnonvapaus ymmärretään ulkoisen ja sisäisen vapauden summaksi, on psykoosi uskonnonvapautta rajoittava tekijä, koska se tekee yksilöstä epäautenttisen ja puuttuu hänen kompetenssiinsa. Psykoosin (myös tahdosta riippumaton) hoito voidaan ymmärtää tällöin yritykseksi palauttaa uskonnonvapaus. Rajoittamalla ulkoista uskonnonvapautta pyritään maksimoimaan ulkoisen ja sisäisen uskonnonvapauden summa. Vaikka psykoottisella ja uskonnollisella todellisuudentulkinnalla on yhtäläisyyksiä, niiden toisistaan erottaminen on tärkeää, koska yksilöllä, jonka todellisuudentulkinta määritellään psykoottiseksi, on oikeus saada hoitoa, kun taas yksilön uskonnollista todellisuudentulkintaa suojaa uskonnonvapaus eikä sitä saa hoitaa sairautena. Lähteiden mukaan psykoottisen ja uskonnollisen todellisuudentulkinnan toisistaan erottaminen diagnostisten kriteerien ja lääketieteellisen tiedon avulla on lääkärin tehtävä. Tutkimuksessani esitän kaksi periaatetta, joiden avulla todellisuudentulkinnat voidaan erottaa toisistaan. Yksinäinen puu ei pala -periaatteen mukaan yksilön todellisuudentulkinta on uskonnollinen, mikäli se jaetaan jossain yhteisössä. Hedelmistään puu tunnetaan -periaatteen mukaan yksilön todellisuudentulkinta on uskonnollinen, mikäli sen terveydelliset ja sosiaaliset seuraukset ovat hyvät. Antipsykiatrinen kritiikki väittää psykiatrian olevan uskonto. Jos väite on tosi, puututaan tahdosta riippumattomassa hoidossa yksilön oikeuteen elää ilman uskontoa, sillä ko. hoidossa olevan psykoottisen potilaan on pakko suostua siihen, että häntä hoidetaan psykiatrian arvojen ja todellisuudentulkinnan mukaan. Vaikuttaa kuitenkin siltä, että jos psykiatria määritellään uskonnoksi, uskonnon käsite kärsii inflaation. Koska psykoottisen potilaan uskonnonvapaus on pohjimmiltaan eettinen kysymys, on tärkeää myöntää psykiatrian arvosidonnaisuus. Tällöin voidaan tehdä tietoisesti moraalisia päätöksiä ja kantaa moraalinen vastuu esimerkiksi diagnoosin määrittelyssä. Psykiatrian voidaan katsoa perustuvan universaaleihin arvoihin samalla tavalla kuin ihmisoikeuksienkin.

The role of phosphorus as a regulator of bloom-forming diazotrophic cyanobacteria in the Baltic Sea

Eutrophication favours harmful algal blooms worldwide. The blooms cause toxic outbreaks and deteriorated recreational and aesthetic values, causing both economic loss and illness or death of humans and animals. The Baltic Sea is the world s only large brackish water habitat with recurrent blooms of toxic cyanobacteria capable of biological fixation of atmospheric nitrogen gas. Phosphorus is assumed to be the main limiting factor, along with temperature and light, for the growth of these cyanobacteria. This thesis evaluated the role of phosphorus nutrition as a regulating factor for the occurrence of nitrogen-fixing cyanobacteria blooms in the Baltic Sea, utilising experimental laboratory and field studies and surveys on varying spatial scales. Cellular phosphorus sources were found to be able to support substantial growth of the two main bloom forming species Aphanizomenon sp. and Nodularia spumigena. However, N. spumigena growth seemed independent of phosphorus source, whereas, Aphanizomenon sp. grew best in a phosphate enriched environment. Apparent discrepancies with field observations and experiments are explained by the typical seasonal temperature dependent development of Aphanizomenon sp. and N. spumigena biomass allowing the two species to store ambient pre-bloom excess phosphorus in different ways. Field experiments revealed natural cyanobacteria bloom communities to be predominantly phosphorus deficient during blooms. Phosphate additions were found to increase the accumulation of phosphorus relatively most in the planktonic size fraction dominated by the nitrogen-fixing cyanobacteria. Aphanizomenon sp. responded to phosphate additions whereas the phosphorus nutritive status of N. spumigena seemed independent of phosphate addition. The seasonal development of phosphorus deficiency is different for the two species with N. spumigena showing indications of phosphorus deficiency during a longer time period in the open sea. Coastal upwelling introduces phosphorus to the surface layer during nutrient deficient conditions in summer. The species-specific ability of Aphanizomenon sp. and N. spumigena to utilise phosphate enrichment of the surface layer caused by coastal upwelling was clarified. Typical bloom time vertical distributions of biomass maxima were found to render N. spumigena more susceptible to advection by surface currents caused by coastal upwellings. Aphanizomenon sp. populations residing in the seasonal thermocline were observed to be able to utilise the phosphate enrichment and a bloom was produced with a two to three week time lag subsequent to the relaxation of upwelling. Consistent high concentrations of dissolved inorganic phosphorus, caused by persistent internal loading of phosphorus, was found to be the main source of phosphorus for large-scale pelagic blooms. External loads were estimated to contribute with only a fraction of available phosphorus for open sea blooms. Remineralization of organic forms of phosphorus along with vertical mixing to the permanent halocline during winter set the level of available phosphorus for the next growth season. Events such as upwelling are important in replenishing phosphate concentrations during the nutrient deplete growth season. Autecological characteristics of the two main bloom forming species favour Aphanizomenon sp. populations in utilising the abundant excess phosphate concentrations and phosphate pulses mediated through upwelling. Whilst, N. spumigena displays predominant phosphorus limited growth mode and relies on more scarce cellular phosphorus stores and presumably dissolved organic phosphorus compounds for growth. The Baltic Sea is hypothesised to be in an inhibited state of recovery due to the extensive historical external nutrient loading, extensive internal phosphorus loading and the substantial nitrogen load caused by cyanobacteria nitrogen fixation. This state of the sea is characterised as a vicious circle .