Nasopharyngeal colonization by pathogenic bacteria: effect of polymorphisms in innate immune genes of young children

Nasopharyngeal bacteria can asymptomatically colonize the nasopharynx of infants and young children but are also associated with the development of respiratory infections and diseases. Such nasopharyngeal bacteria include Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae and Staphylococcus aureus. The host defense against invading pathogens is largely relies germline-encoded pattern recognition receptors (PRR), which are expressed on the cells of innate immunity, and different cytokines. These include toll-like receptors (TLR), mannose-binding lectin (MBL) and different cytokines such as IL-17A. Single nucleotide polymorphisms (SNP) in these receptors and cytokines have been reported. The aim of this study was to investigate genetic polymorphisms in the genes for TLR2, 3 and 4, MBL as well as for IL-17A and their associations with nasopharyngeal pathogenic bacterial colonization during a two-year follow-up. The study revealed that polymorphisms in TLRs, MBL2 and IL17A are associated with the nasopharyngeal bacterial colonization in young children. Healthy young (2.6 months of age) children with variant types of MBL2, TLR2 R753Q or TLR4 D299G had an increased risk to be colonized by S. pneumonia, S. aureus or M. catarrhalis, respectively. Moreover, variant types of MBL2 in healthy children with might facilitate human rhinovirus (HRV)-induced S. pneumoniae colonization at 2.6 months of age. The polymorphism of TLR4 D299G was shown to be associated with M. catarrhalis colonization throughout the whole two-year follow-up (2.6, 13 and 24 months of age) and also with the bacterial load of this pathogen. Also, the polymorphism of IL17A G152A was shown to be associated with increased risk to be colonized by S. pneumoniae at 13 and 24 months of age. Furthermore, the results suggest that IL17A G152A has an effect on production of serum IL-17A already at young age. In conclusion, the results of this study indicate that polymorphisms in the key PRRs and IL17A seem to play an important role to colonization of S. pneumoniae, M. catarrhalis, and S. aureus in healthy young Finnish children. The nasopharyngeal colonization by these pathogenic bacteria may further promote the development of respiratory infections and may be related to development of asthma and allergy in the later life of children. These findings offer a possible explanation why some children have more respiratory infections than other children and provide a rational basis for future studies in this field.

Safety and outcome of coronary interventions with special reference to anticoagulation and stent type

University of Turku, Faculty of Medicine, Department of Cardiology and Cardiovascular Medicine, Doctoral Programme of Clinical Investigation, Heart Center, Turku University Hospital, Turku, Finland Division of Internal Medicine, Department of Cardiology, Seinäjoki Central Hospital, Seinäjoki, Finland Heart Center, Satakunta Central Hospital, Pori, Finland Annales Universitatis Turkuensis Painosalama Oy, Turku, Finland 2015 Antithrombotic therapy during and after coronary procedures always entails the challenging establishment of a balance between bleeding and thrombotic complications. It has been generally recommended to patients on long-term warfarin therapy to discontinue warfarin a few days prior to elective coronary angiography or intervention to prevent bleeding complications. Bridging therapy with heparin is recommended for patients at an increased risk of thromboembolism who require the interruption of anticoagulation for elective surgery or an invasive procedure. In study I, consecutive patients on warfarin therapy referred for diagnostic coronary angiography were compared to control patients with a similar disease presentation without warfarin. The strategy of performing coronary angiography during uninterrupted therapeutic warfarin anticoagulation appeared to be a relatively safe alternative to bridging therapy, if the international normalized ratio level was not on a supratherapeutic level. In-stent restenosis remains an important reason for failure of long-term success after a percutaneous coronary intervention (PCI). Drug-eluting stents (DES) reduce the problem of restenosis inherent to bare metal stents (BMS). However, a longer delay in arterial healing may extend the risk of stent thrombosis (ST) far beyond 30 days after the DES implantation. Early discontinuation of antiplatelet therapy has been the most important predisposing factor for ST. In study II, patients on long-term oral anticoagulant (OAC) underwent DES or BMS stenting with a median of 3.5 years’follow-up. The selective use of DESs with a short triple therapy seemed to be safe in OAC patients, since late STs were rare even without long clopidogrel treatment. Major bleeding and cardiac events were common in this patient group irrespective of stent type. In order to help to predict the bleeding risk in patients on OAC, several different bleeding risk scorings have been developed. Risk scoring systems have also been used also in the setting of patients undergoing a PCI. In study III, the predictive value of an outpatient bleeding risk index (OBRI) to identify patients at high risk of bleeding was analysed. The bleeding risk seemed not to modify periprocedural or long-term treatment choices in patients on OAC after a percutaneous coronary intervention. Patients with a high OBRI often had major bleeding episodes, and the OBRI may be suitable for risk evaluation in this patient group. Optical coherence tomography (OCT) is a novel technology for imaging intravascular coronary arteries. OCT is a light-based imaging modality that enables a 12–18 µm tissue axial resolution to visualize plaques in the vessel, possible dissections and thrombi as well as, stent strut appositions and coverage, and to measure the vessel lumen and lesions. In study IV, 30 days after titanium-nitride-oxide (TITANOX)-coated stent implantation, the binary stent strut coverage was satisfactory and the prevalence of malapposed struts was low as evaluated by OCT. Long-term clinical events in patients treated with (TITANOX)-coated bio-active stents (BAS) and paclitaxel-eluting stents (PES) in routine clinical practice were examined in study V. At the 3-year follow-up, BAS resulted in better long-term outcome when compared with PES with an infrequent need for target vessel revascularization. Keywords: anticoagulation, restenosis, thrombosis, bleeding, optical coherence tomography, titanium

Electrical status epilepticus during sleep. Continuous spikes and waves during sleep

ABSTRACT Maria Peltola Electrical status epilepticus during sleep – Continuous spikes and waves during sleep Department of Clinical Neurophysiology, University of Turku Department of Clinical Neurophysiology and Department of Pediatric Neurology, Children’s Hospital, Helsinki University Central Hospital Annales Universitatis Turkuensis, Medica-Odontologica, Turku, Finland, 2014 Background: Electrical status epilepticus during sleep (ESES) is an EEG phenomenon of frequent spikes and waves occurring in slow sleep. ESES relates to cognitive deterioration in heterogeneous childhood epilepsies. Validated methods to quantitate ESES are missing. The clinical syndrome, called epileptic encephalopathy with continuous spikes and waves during sleep (CSWS) is pharmacoresistant in half of the patients. Limited data exists on surgical treatment of CSWS. Aims and methods: The effects of surgical treatment were studied by investigating electroclinical outcomes in 13 operated patients (nine callosotomies, four resections) with pharmacoresistant CSWS and cognitive decline. Secondly, an objective paradigm was searched for assessing ESES by the semiautomatic quantification of spike index (SI) and measuring spike strength from EEG. Results: Postoperatively, cognitive deterioration was stopped in 12 (92%) patients. Three out of four patients became seizure-free after resective surgery. Callosotomy resulted in greater than 90% reduction of atypical absences in six out of eight patients. The preoperative propagation of ESES from one hemisphere to the other was associated with a good response. Semiautomatic quantification of SI was a robust method when the maximal interspike interval of three seconds was used to determine the “continuous” discharge in ten EEGs. SI of the first hour of sleep appeared representative of the whole night SI. Furthermore, the spikes’ root mean square was found to be a stable measure of spike strength when spatially integrated over multiple electrodes during steady NREM sleep. Conclusions: Patients with pharmacoresistant CSWS, based on structural etiology, may benefit from resective surgery or corpus callosotomy regarding both seizure outcome and cognitive prognosis. The semiautomated SI quantification, with proper userdefined settings and the new spatially integrated measure of spike strength, are robust and promising tools for quantifying ESES. Keywords: Electrical status epilepticus during sleep, ESES, continuous spikes and waves during sleep, CSWS, epilepsy surgery, spike index, spike strength, RMS TIIVISTELMÄ Maria Peltola Unenaikainen sähköinen status epilepticus Kliininen neurofysiologia, Turun yliopisto Kliininen neurofysiologia ja lastenneurologia, Lasten ja nuorten sairaala, Helsingin yliopistollinen keskussairaala Annales Universitatis Turkuensis, Medica-Odontologica, Turku, Suomi, 2014 Tausta: Sähköinen status epilepticus unessa (ESES) on aivosähkökäyrä (EEG)-ilmiö, jossa hidasaaltounen aikana esiintyy tiheä piikkihidasaaltopurkaus. ESES:n kvantifioimiseen ei ole olemassa validoituja menetelmiä. ESES on liitetty kognitiivisen tason laskuun ja tällöin puhutaan CSWS (continuous spikes and waves during sleep) - oireyhtymästä. CSWS ei vastaa lääkehoitoon puolella potilaista ja sen epilepsiakirurgisesta hoidosta on olemassa vain vähän tietoa. Tavoitteet ja menetelmät: Selvitimme retrospektiivisesti epilepsiakirurgian vaikusta elektrokliinisiin löydöksiin 13:lla lääkeresistenttiä CSWS-oireyhtymää sairastavalla lapsella, joilla oli rakenteellinen aivojen poikkeavuus. Toinen tavoite oli löytää objektiivinen puoliautomaattinen tapa mitata purkauksen määrää ja piikkien voimakkuutta EEG:stä. Tulokset: Kognitiivisen tason jatkuva heikentyminen loppui 12 (92 %) potilaalla leikkauksen jälkeen. Kolme neljästä resektiopotilaasta tuli kohtauksettomaksi. Kallosotomian jälkeen kuudella kahdeksasta potilaasta päivittäiset kohtaukset vähenivät yli 90 %:lla. Purkauksen leviäminen leikkausta edeltävästi vain yhdestä hemisfääristä toiseen liittyi hyvään leikkaushoitovasteeseen. Piikki-indeksi, jossa käytetään jatkuvan purkauksen määritelmänä maksimissaan kolmea sekuntia piikkien välillä, osoittautui luotettavaksi menetelmäksi ESES:n kvantifioimiseen. Useammasta elektrodista integroitu piikkien neliöllinen keskiarvo oli piikin voimakkuuden vakaa mitta häiriintymättömässä NREM-unessa. Päätelmät: Lääkehoidolle vastaamatonta CSWS:ää sairastavat potilaat, joilla on rakenteellinen aivopoikkeavuus ja yhdensuuntainen purkauksen leviämismalli, näyttävät kohtausten vähenemisen lisäksi hyötyvän epilepsiakirurgiasta kognitiivisesti. Puoliautomaattinen piikki-indeksin kvantifiointi sopivilla käyttäjäasetuksilla ja uusi spatiaalisesti integroitu piikin voimakkuuden mittari ovat stabiileja ja lupaavia ESES:n kvantitatiivisia mittareita. Avainsanat: Unenaikainen sähköinen status epilepticus, ESES, CSWS, epilepsiakirurgia, piikki-indeksi, piikin voimakkuus, neliöllinen keskiarvo

Suomen kirkon 800-vuotisjuhlassa (Valtioneuvoston tervehdys Turun Tuomiokirkossa 19.5.1955)

Puhe

Kauppias, kaupunki, kruunu : Turun porvariyhteisö ja talouden organisaatio varhaiskeskiajalta 1570-luvulle

Summary: The merchant, the town and the crown : the burgher community of Turku and economic organization from the early Middle Ages to the 1570's

Suomalaisten ulkomainen opinkäynti ennen Turun akatemian perustamista 1640

Summary: Finnish study abroad before the foundation of the Royal Academy of Turku (Academia Aboensis) in 1640