Lactobacillus bacteremia, with special focus on the safety of probiotic Lactobacillus rhamnosus GG

Lactobacilli are gram positive rods, which belong to normal oropharyngeal, gastrointestinal and urogenital flora. They are widely used in food industry and as food additives. Although their virulence is presumed to be very low, opportunistic bacteremic infections, especially in immunocompromised hosts, have been detected. In the present study, the possible effects of increasing probiotic use of Lactobacillus rhamnosus GG (LGG) on the occurrence of bacteremia due to lactobacilli was evaluated on population level. In Finland, 90 Lactobacillus bacteremia cases were reported to the National Infectious Disease Register maintained by National Public Health Institute, during 1995-2000. Their proportion of all bacteremia cases was on average 0.24%, corresponding to 0.3 cases/100 000 inhabitants annually. In the Helsinki University Central Hospital district the corresponding proportion of all bacteremia cases was observed during 1990-2000. Despite LGG intake increased six folded no increasing trend in the occurrence of lactobacilli bacteremia was seen. A total of 85 Lactobacillus sp. blood isolates collected from different human bacteremic cases were characterised and compared with the commercial probiotic LGG strain. In species characterisation 46 L. rhamnosus strains, 12 L. fermentum and L. casei strains each, three each of L. gasseri, L. salivarius and L. jensenii species, two L. curvatus, and one each of L. plantarum, L. sakei, L. zeae and L. reuteri species were detected. Nearly half of the L. rhamnosus findings turned out to be indistinguishable from the probiotic LGG strain. Common predisposing factors to Lactobacillus bacteremia were immunosuppression, prior prolonged hospitalisation and prior surgical interventions. Severe or fatal comorbidities were found in 82% of the patients. Mortality at one month was 26% and severe underlying diseases were a significant predictor of death (OR 15.8). Antimicrobial susceptibility of Lactobacillus strains was species dependent. The Lactobacillus isolates were generally susceptible to imipenem, piperacillin-tazobactam, clindamycin and erythromycin, whereas all other than L. gasseri and L. jensenii species were not at all susceptible to vancomycin. The susceptibility to cephalosporin varied greatly even within species why they might not be recommended for treatment of Lactobacillus infections. The effect and safety of probiotic LGG preparation in amelioration of gastric symptoms and diarrhea in HIV-infected patients was evaluated. No significant differences in gastrointestinal symptoms or diarrhoea in LGG treated patients compared to placebo could be found. LGG was well tolerated with no adverse effects including bacteremic outbreaks could be observed. The use of probiotic LGG can be regarded safe in this immunocompromised patient group.

Damp building moulds: Assessment of sensitization in patients and studies into mechanisms of airway inflammation using experimental models

Exposure to water-damaged buildings and the associated health problems have evoked concern and created confusion during the past 20 years. Individuals exposed to moisture problem buildings report adverse health effects such as non-specific respiratory symptoms. Microbes, especially fungi, growing on the damp material have been considered as potential sources of the health problems encountered in these buildings. Fungi and their airborne fungal spores contain allergens and secondary metabolites which may trigger allergic as well as inflammatory types of responses in the eyes and airways. Although epidemiological studies have revealed an association between damp buildings and health problems, no direct cause-and-effect relationship has been established. Further knowledge is needed about the epidemiology and the mechanisms leading to the symptoms associated with exposure to fungi. Two different approaches have been used in this thesis in order to investigate the diverse health effects associated with exposure to moulds. In the first part, sensitization to moulds was evaluated and potential cross-reactivity studied in patients attending a hospital for suspected allergy. In the second part, one typical mould known to be found in water-damaged buildings and to produce toxic secondary metabolites was used to study the airway responses in an experimental model. Exposure studies were performed on both naive and allergen sensitized mice. The first part of the study showed that mould allergy is rare and highly dependent on the atopic status of the examined individual. The prevalence of sensitization was 2.7% to Cladosporium herbarum and 2.8% to Alternaria alternata in patients, the majority of whom were atopic subjects. Some of the patients sensitized to mould suffered from atopic eczema. Frequently the patients were observed to possess specific serum IgE antibodies to a yeast present in the normal skin flora, Pityrosporum ovale. In some of these patients, the IgE binding was partly found to be due to binding to shared glycoproteins in the mould and yeast allergen extracts. The second part of the study revealed that exposure to Stachybotrys chartarum spores induced an airway inflammation in the lungs of mice. The inflammation was characterized by an influx of inflammatory cells, mainly neutrophils and lymphocytes, into the lungs but with almost no differences in airway responses seen between the satratoxin producing and non-satratoxin producing strain. On the other hand, when mice were exposed to S. chartarum and sensitized/challenged with ovalbumin the extent of the inflammation was markedly enhanced. A synergistic increase in the numbers of inflammatory cells was seen in BAL and severe inflammation was observed in the histological lung sections. In conclusion, the results in this thesis imply that exposure to moulds in water damaged buildings may trigger health effects in susceptible individuals. The symptoms can rarely be explained by IgE mediated allergy to moulds. Other non-allergic mechanisms seem to be involved. Stachybotrys chartarum is one of the moulds potentially responsible for health problems. In this thesis, new reaction models for the airway inflammation induced by S. chartarum have been found using experimental approaches. The immunological status played an important role in the airway inflammation, enhancing the effects of mould exposure. The results imply that sensitized individuals may be more susceptible to exposure to moulds than non-sensitized individuals.

Complete genome sequence of a novel zantedeschia mild mosaic virus isolate: The first report from Australia and from Alocasia sp

The complete genome of an Australian isolate of zantedeschia mild mosaic virus (ZaMMV) causing mosaic symptoms on Alocasia sp. (designated ZaMMVAU) was cloned and sequenced. The genome comprises 9942 nucleotides (excluding the poly-A tail) and encodes a polyprotein of 3167 amino acids. The sequence is most closely related to a previously reported ZaMMV isolate from Taiwan (ZaMMV-TW), with 82 and 86 % identity at the nucleotide and amino acid level, respectively. Unlike the amino acid sequence of ZaMMV-TW, however, ZaMMV-AU does not contain a polyglutamine stretch at the N-terminus of the coat-protein-coding region upstream of the DAG motif. This is the first report of ZaMMV from Australia and from Alocasia sp.

Samanaikaisen alkoholiriippuvuuden ja vakavan masennuksen hoito memantiinilla ja essitalopraamilla - tulos ja ennustetekijät

Samanaikainen alkoholiriippuvuus ja vakava masennustila on haasteellista sekä lääketieteelliselle hoidolle että tutkimukselle. Tämä oireyhtymä on yksi yleisimmistä psykiatrisista häiriöistä niin Yhdysvalloissa kuin Suomessakin. Potilaiden ja heidän omaistensa inhimillisen kärsimyksen lisäksi myös kokonaistaloudelliset terveydenhoidolliset kustannukset ovat suuret tämän oireyhtymän hoidossa: niiden arvioidaan olevan yli neljäkymmentä prosenttia korkeammat kuin pelkän depression kohdalla. Tässä tutkimuksessa pyrittiin löytämään uusia hoidollisia vaihtoehtoja alkoholiriippuvuudesta ja vakavasta masennuksesta yhtäaikaisesti kärsivien potilaiden hoidossa. Tutkimukseen osallistui 80 potilasta Helsingin kaupungin kolmelta A-klinikalta. Kyseessä oli kaksoissokko, randomisoitu, kahden eri tavalla vaikuttavan lääkkeen, essitalopraamin (selektiivinen serotoniinin takaisinoton estäjä) ja memantiinin (glutamaatin NMDA reseptorin ei-kilpaileva estäjä) vertaileva tutkimus. Potilaiden oireiden kulkua seurattiin 26 viikkoa depressioon, ahdistuneisuuteen, kogniitioihin, elämänlaatuun ja alkoholin käyttöön liittyvillä mittareilla. Tämän jälkeen tarkasteltiin hoitovastetta alkutilanne- ja taustamuuttujien valossa. Pyrkimyksenä oli löytää joitakin ennustekijöitä, joiden pohjalta kliinikko voisi tehdä hoitoratkaisunsa näiden potilaiden hoidossa. Molemmat lääkkeet vähensivät merkittävästi sekä masennusta että ahdistuneisuutta, eikä essitalopraami- ja memantiiniryhmien välillä ollut tilastollisesti merkitsevää eroa. Kognitiiviset toiminnot olivat lähtövaiheessa normatiivisella tasolla. Elämän laatu parani molemmissa hoitoryhmissä. Alkoholimittareilla AUDIT (alkoholihäiriöiden tunnistusmittari) ja OCDS (pakkomielteisen ja pakkotoimintoisen alkoholinkäytön mittari) paranivat molemmissa hoitoryhmissä. Varhainen ensimmäisen vakavan masennuksen episodin alku näytti ennakoivan huonoa vastetta essitalopraamille, mutta ei memantiinille, mitattuna Montgomery-Åsberg depression rating scale -asteikolla. Toisaalta myöhäinen ensimmäisen masennuksen episodi näytti ennakoivan hyvää hoitovastetta essitalopraamille. Niinpä ensimmäisen masennuksen alkamisikä saattaisi olla käyttökelpoinen ennustekijä näille lääkkeille. Varhainen humalahakuisen juomisen alkamisikä näytti ennustavan huonoa hoitovastetta molemmille lääkkeille, erityisesti essitalopraamille, mitattuna AUDIT-mittarilla. Aktiivinen alkoholinkäyttö tutkimuksen alkaessa ennakoi tutkimuksen keskeyttämistä. HTTLPR-geenin L-alleeli näytti ennustavan parempaa hoitovastetta essitalopraamille masennukseen kuin S-alleeli.

Monimuotoisuus ja esteettömyys : Näkövammaisten asiantuntijoiden työelämäkokemuksia

The purpose of this study is to analyse education, employment, and work-life experiences of visually impaired persons in expert jobs. The empirical data consists of 30 thematic interviews (24 visually impaired persons, 1 family-member of a visually impaired person, 5 persons working with diversity issues), of supplementary articles, and of statistics on the socio-economic status of the visually impaired. The interviewees experiences of education and employment have been analysed by a qualitative method. The analysis has been deepened by reflecting it against the recent discussion on the concept of diversity. The author s methodological choice as a disability researcher has been to treat the interviewees as co-researchers rather than objects of research. Accessibility in its different forms is a prerequisite of diversity in the workplace, and this study examines what kind of accessibility is required by visually impaired professionals. Access to working life depends on the attitudes prejudices and expectations that society has towards a minority group. Social accessibility is connected with internal relationships in the workplace, and achieving social accessibility is a bilateral process. Information technology has revolutionised the visually impaired people s possibilities of accessing information and performing expert tasks. Accessible environment, good mobility skills, and transportation services enable visually impaired employees to get to their workplaces and to navigate there with ease. Integration has raised the level of education and widened the selection of career options for the visually impaired. However, even visually impaired people with academic degrees often need employment support services. Visually impaired professionals are mainly employed in the public and third sector. Achieving diversity in the labour market is a multiactor process. Social support services are needed, as well as courage and readiness from employers to hire people with disabilities. The organisations of the visually impaired play an important role in affecting the attitudes and providing peer support. Visually impaired employees need good professional skills, blindness skills, and social courage, and they need to be comfortable with their disability. In the workplace, diversity may actualise as diverse ways of working: the work is done by using technical aids or other means of compensating for the lack of eyesight. When an employee must find compensatory solutions for disability-related limitations at work, this will also develop his/her problem-solving abilities. Key words: visually impaired, diversity, accessibility, working life

Lähellä, mutta niin kaukana : Tutkimus naisten muuttoliikkeestä Suomen ja uudelleen itsenäistyneen Viron välillä

Immigration is one of the most topical international issues of our time. Worldwide, the number of immigrants has doubled over the last twenty years, and migration patterns have become so diversified that they now constitute a kind of “chaos”. The number and significance of women as migrants has also increased, which is earning women growing attention among scholars. This study looks at the migration of women, in particular mothers of small children, in both directions between Finland and Estonia, following the latter’s re- independence. The data consists of in-depth interviews conducted in 2005 with 24 Finnish and 24 Estonian immigrant women. The focus was on the women’s expectations and experiences of their new country of residence, acculturation – i.e. adjusting to a new environment, social networks in the country of origin and the new country, and models of motherhood following immigration. The primary research question was formulated as follows: Which factors have influenced the formation of female immigrants’ social ties, thus contributing to the formation of motherhood strategies and afecting internal family dynamics in the new country? The research consists of four previously published independent articles as well as a summary chapter. The study’s findings indicate that Finnish and Estonian women migrated for diferent reasons and at diferent times, and that their migration patterns also difered. Estonian migration occurred mainly in the 1990s, and most immigrants intended to return later to their country of origin. Regardless of the reason for migrating that they gave to immigration officials, other key reasons often included the desire for a more stable living environment and better income. Only four of the Estonian women had immigrated together with an Estonian husband, while two- thirds came because of marriage to a Finnish man. Most of the Finnish women, on the other hand, migrated after 2000 and either came with their family as a result of a spouse’s job transfer, or came by themselves to further their studies. In most cases, the migration was a temporary solution intended to promote one’s own or one’s spouse’s career advancement. Because the reasons for migrating were diferent between Finnish and Estonian women, their expectations of the new country and their status in it were also diferent. In terms of both social and economic standing, the position of Finnish immigrants was categorically better. The reason for migrating had an impact on one’s orientation toward the receiving society. Estonian women and Finns who migrated for marriage or edu cational reasons became immediately active in forming institutional and social ties in the new society. Conversely, the women had migrated because of work had little contact with Estonian society, and their social networks consisted of other Finnish immigrants. Furthermore, they maintained strong institutional and social ties to Finland and therefore felt no need to anchor themselves to Estonian society. The Finnish and Estonian women who were better integrated into the receiving country also maintained strong social ties to their country of origin. Women who became integrated into the receiving country as a result of giving birth to children utilized various services directed at families with children. In part, such services conveyed to the women the conceptions that were prevalent in the surrounding society concerning the treatment of children and the expectations on mothers, both of which difer to some extent in Finland and Estonia. had an impact on strategies of motherhood, internal family dynamics, and gender Regardless of the reason for migrating, or the country of origin, immigration equality. Most Estonian women had to do without the child-care help provided by relatives; before immigrating, some women had even had daily child-care assistance from family members. However, Estonian women who were married to Finns did receive help from the spouse and sometimes also the spouse’s relatives. Conversely, Finnish women who had immigrated because of a spouse’s job transfer were faced with the opposite situation, in which they bore the main responsibility for domestic work and child care. They were, however, in a position to pay for domestic help. Hence, the women who had integrated into a new society had to construct their own perceptions of motherhood by reconciling the motherhood models of both the cause of a spouse’s job transfer found that being a stay-at-home mother challenged previously self-evident behaviors. Receiving country and the country of origin, whereas women who had migrated because of a spouse’s job transfer found that being a stay-at-home mother challenged previously self-evident behaviors.