Thrombophilia and direct thrombin inhibitor lepirudin clinical and monitoring aspects

Thrombophilia (TF) predisposes both to venous and arterial thrombosis at a young age. TF may also impact the thrombosis or stenosis of hemodialysis (HD) vascular access in patients with end-stage renal disease (ESRD). When involved in severe thrombosis TF may associate with inappropriate response to anticoagulation. Lepirudin, a potent direct thrombin inhibitor (DTI), indicated for heparin-induced thrombocytopenia-related thrombosis, could offer a treatment alternative in TF. Monitoring of narrow-ranged lepirudin demands new insights also in laboratory. The above issues constitute the targets in this thesis. We evaluated the prevalence of TF in patients with ESRD and its impact upon thrombosis- or stenosis-free survival of the vascular access. Altogether 237 ESRD patients were prospectively screened for TF and thrombogenic risk factors prior to HD access surgery in 2002-2004 (mean follow-up of 3.6 years). TF was evident in 43 (18%) of the ESRD patients, more often in males (23 vs. 9%, p=0.009). Known gene mutations of FV Leiden and FII G20210A occurred in 4%. Vascular access sufficiently matured in 226 (95%). The 1-year thrombosis- and stenosis-free access survival was 72%. Female gender (hazards ratio, HR, 2.5; 95% CI 1.6-3.9) and TF (HR 1.9, 95% CI 1.1-3.3) were independent risk factors for the shortened thrombosis- and stenosis-free survival. Additionally, TF or thrombogenic background was found in relatively young patients having severe thrombosis either in hepatic veins (Budd-Chiari syndrome, BCS, one patient) or inoperable critical limb ischemia (CLI, six patients). Lepirudin was evaluated in an off-label setting in the severe thrombosis after inefficacious traditional anticoagulation without other treatment options except severe invasive procedures, such as lower extremity amputation. Lepirudin treatments were repeatedly monitored clinically and with laboratory assessments (e.g. activated partial thromboplastin time, APTT). Our preliminary studies with lepirudin in thrombotic calamities appeared safe, and no bleeds occurred. An effective DTI lepirudin calmed thrombosis as all patients gradually recovered. Only one limb amputation was performed 3 years later during the follow-up (mean 4 years). Furthermore, we aimed to overcome the limitations of APTT and confounding effects of warfarin (INR of 1.5-3.9) and lupus anticoagulant (LA). Lepirudin responses were assessed in vitro by five specific laboratory methods. Ecarin chromogenic assay (ECA) or anti-Factor IIa (anti-FIIa) correlated precisely (r=0.99) with each other and with spiked lepirudin in all plasma pools: normal, warfarin, and LA-containing plasma. In contrast, in the presence of warfarin and LA both APTT and prothrombinase-induced clotting time (PiCT®) were limited by non-linear and imprecise dose responses. As a global coagulation test APTT is useful in parallel to the precise chromogenic methods ECA or Anti-FIIa in challenging clinical situations. Lepirudin treatment requires multidisciplinary approach to ensure appropriate patient selection, interpretation of laboratory monitoring, and treatment safety. TF seemed to be associated with complicated thrombotic events, in venous (BCS), arterial (CLI), and vascular access systems. TF screening should be aimed to patients with repeated access complications or prior unprovoked thromboembolic events. Lepirudin inhibits free and clot-bound thrombin which heparin fails to inhibit. Lepirudin seems to offer a potent and safe option for treatment of severe thrombosis. Multi-centered randomized trials are necessary to assess the possible management of complicated thrombotic events with DTIs like lepirudin and seek prevention options against access complications.

Uso del pronombre personal sujeto de la primera persona del singular en español y portugués hablados: factores semánticos y pragmáticos

Tutkimuksen aihe on subjektipronominin ei-pakollinen käyttö finiittisten verbimuotojen yhteydessä espanjan ja portugalin kielessä. Tutkimuskohteena ovat yksikön ensimmäisen persoonan verbimuodot Espanjassa ja Portugalissa kerätyissä puhekielen korpuksissa. Tutkimuksen tarkoitus on selvittää, mitkä semanttiset ja pragmaattiset tekijät vaikuttavat subjektipronominin ei-pakollisen käytön yleisyyteen ja mitä systemaattisia eroja subjektipronominin käytössä on espanjan ja portugalin välillä. Tutkimus kuuluu korpuslingvistiikan alaan ja ensisijaisena tutkimusmetodina on kvantitatiivinen vertailu. Tutkimus osoittaa, että yksikön ensimmäisen persoonan subjektipronominin ei-pakollinen käyttö on käytännössä kaikissa konteksteissa yleisempää portugalissa kuin espanjassa. Tätä eroa voidaan selittää kielten konstituenttirakenteen typologisella erilaisuudella. Subjektin semanttinen rooli on tutkimuksen perusteella sidoksissa subjektipronominin käyttöön enemmän espanjassa kuin portugalissa, mutta kummassakaan kielessä subjektipronominin käyttöä ei voida selittää pelkästään subjektin semanttisella roolilla. Molemmissa kielissä samanviitteisyys edellisen subjektin kanssa vähentää subjektipronominin käyttöä, kun taas subjektipronominin ei-referentiaalinen käyttö ja toisaalta verbin ilmaiseman toiminnan irreaalisuus lisäävät sitä. Tutkimustulokset antavat aihetta lisätutkimukseen pronominien ja verbien ei-referentiaalisesta ja irreaalisesta käytöstä espanjassa ja portugalissa sekä typologi-seen tutkimukseen subjektipronominien käyttöön vaikuttavista tekijöistä eri kielissä.

Seasonal fluctuations in blue-green algae, especially in heterocystous species in polluted coastal waters off Helsinki city, in the northern part of the Gulf of Finland

Tiivistelmä

Choosing the Arranged One, Arranging the Chosen One – Imagining an Indian Modernity: Reconciling Love, Marriage and Family On and Off the Screen

This is a study on the changing practices of kinship in Northern India. The change in kinship arrangements, and particularly in intermarriage processes, is traced by analysing the reception of Hindi popular cinema. Films and their role and meaning in people´s lives in India was the object of my research. Films also provided me with a methodology for approaching my other subject-matters: family, marriage and love. Through my discussion of cultural change, the persistence of family as a core value and locus of identity, and the movie discourses depicting this dialogue, I have looked for a possibility of compromise and reconciliation in an Indian context. As the primary form of Indian public culture, cinema has the ability to take part in discourses about Indian identity and cultural change, and alleviate the conflicts that emerge within these discourses. Hindi popular films do this, I argue, by incorporating different familiar cultural narratives in a resourceful way, thus creating something new out of the old elements. The final word, however, is the one of the spectator. The “new” must come from within the culture. The Indian modernity must be imaginable and distinctively Indian. The social imagination is not a “Wild West” where new ideas enter the void and start living a life of their own. The way the young women in Dehra Dun interpreted family dramas and romantic movies highlights the importance of family and continuity in kinship arrangements. The institution of arranged marriage has changed its appearance and gained new alternative modes such as love cum arranged marriage. It nevertheless remains arranged by the parents. In my thesis I have offered a social description of a cultural reality in which movies act as a built-in part. Movies do not work as a distinct realm, but instead intertwine with the social realities of people as a part of a continuum. The social imagination is rooted in the everyday realities of people, as are the movies, in an ontological and categorical sense. According to my research, the links between imagination and social life were not so much what Arjun Appadurai would call global and deterritorialised, but instead local and conventional.