Venous thromboembolism and obstruction after pacemaker implantation. - A Prospective Study of 150 Consecutive Cardiac Pacing Device Implantations

Background: Pacemaker implantation (PMI) may predispose to venous thromboembolism (VTE) and obstruction (VO). This prospective study aimed at quantifying changes in venous calibers, and at determining the incidence of symptomatic and asymptomatic VTE/VO after PMI. Further goals included an assessment of the role of transesophageal echocardiography (TEE) in the diagnosis of lead-related central venous thrombi (CVT), and determination of predictors for VTE/VO. Methods: 150 (mean age 67; 61% male) consecutive patients with first PMI were enrolled and followed for 6 months. Contrast venography was performed at baseline and 6 months after PMI to measure venous diameters, and to detect stenosis, total occlusions and thrombi. TEE was conducted in 66 patients. Based on clinical suspicion, work-up for pulmonary embolism (PE) or acute deep vein thrombosis (DVT) were performed as needed. A total of 50 cases underwent longer-term (mean 2.4 years) follow-up venography. All cases with VTE/VO during the initial 6 months, and their matched controls, were selected for a case-control study focused on possible predictive role of laboratory and patient-related factors for the development of VTE/VO. Results: 10 (7 %) patients were found to have baseline venous abnormalities (e.g. 8 obstructions). Mean venous diameters diminished significantly during the first 6 months, but no further reduction occurred in late follow-up. New VO was discovered in 19 patients (14 %; 14 stenosis, 5 total occlusions; all asymptomatic). Small non-obstructive thrombi were found in 20/140 (14 %) 6-month venograms. TEE at 6 months disclosed CVT in 6 (9 %) patients. One (0.7 %) patient had acute symptomatic upper-extremity DVT, and PE was discovered in 5/150 (3.3 %) patients during the first 6 months with no further cases thereafter. At 6 months, the total number of cases with VTE/VO amounted to 47 (31.3 %). Additionally, the later 2-year venograms (n=50) disclosed 4 (8 %) total occlusions and 1 (2 %) stenosis. In the case-control study, no parameter was predictive of venous end-points as a single variable, but there appeared to be significant clustering of traditional VTE risk-factors among the cases. Laboratory parameters showed a definite acute hypercoagulative state induced by PMI, but its degree did not predict subsequent development of VTE/VO. Conclusions: This study shows that VTE/VO is relatively common after PMI with an overall incidence of at least 30 %. Although the majority of the lesions are asymptomatic and clinically benign, cases of PE were also encountered, and totally occluded veins may hamper future upgrading or replacement of pacing system. Venous complications seem difficult to prognosticate as firm predictors were not identified from a wide range of parameters analyzed in this study, although clustering of classic VTE risk factors may be a predisposing factor. Parameters related to implantation procedure or pacing systems and the severity of implantation-induced trauma did not emerge as predictors.

Genesis and Emplacement of Carbonatites and Lamprophyres in the Svecofennian Domain

A small carbonatite dyke swarm has been identified at Naantali, southwest Finland. Several swarms of shoshonitic lamprophyres are also known along the Archean-Proterozoic boundary in eastern Finland and northwest Russia. These intrusions, along with the carbonatite intrusion at Halpanen, eastern Finland, represent a stage of widespread low-volume mantle-sourced alkaline magmatism in the Svecofennian Domain. Using trace element and isotope geochemistry coupled with precise geochronology from these rocks, a model is presented for the Proterozoic metasomatic evolution of the Fennoscandian subcontinental lithospheric mantle. At ~2.2-2.06 Ga, increased biological production in shallow seas linked to continental rifting, resulted in increased burial rates of organic carbon. Subduction between ~1.93-1.88 Ga returned organic carbon-enriched sediments of mixed Archean and Proterozoic provenance to the mantle. Dehydration reactions supplied water to the mantle wedge, driving arc volcanism, while mica, amphibole and carbonate were brought deeper into the mantle with the subducting slab. The cold subducted slab was heated conductively from the surrounding warm mantle, while pressures continued to gradually increase as a result of crustal thickening. The sediments began to melt in a two stage process, first producing a hydrous alkaline silicate melt, which infiltrated the mantle wedge and crystallised as metasomatic veins. At higher temperatures, carbonatite melt was produced, which preferentially infiltrated the pre-existing metasomatic vein network. At the onset of post-collisional extension, deep fault structures formed, providing conduits for mantle melts to reach the upper crust. Low-volume partial melting of the enriched mantle at depths of at least 110 km led to the formation of first carbonatitic magma and subsequently lamprophyric magma. Carbonatite was emplaced in the upper crust at Naantali at 1795.7 ± 6.8 Ma; lamprophyres along the Archean-Proterozoic boundary were emplaced between 1790.1 ± 3.3 Ma and 1781 ± 20 Ma.

Alpha2-Adrenoceptor-mediated vascular responses induced by dexmedetomidine

Alpha2-Adrenoceptors are cell-surface G protein coupled receptors that mediate many of the effects of the catecholamines noradrenaline and adrenaline. The three human α2-adrenoceptor subtypes are widely expressed in different tissues and organs, and they mediate many different physiological and pharmacological effects in the central and peripheral nervous system and as postsynaptic receptors in target organs. Previous studies have demonstrated that α2-adrenoceptors mediate both vascular constriction and dilatation in humans. Large inter-individual variation has been observed in the vascular responses to α2-adrenoceptor activation in clinical studies. All three receptor subtypes are potential drug targets. It was therefore considered important to further elucidate the details of adrenergic vascular regulation and its genetic variation, since such knowledge may help to improve the development of future cardiovascular drugs and intensive care therapies. Dexmedetomidine is the most selective and potent α2-adrenoceptor agonist currently available for clinical use. When given systemically, dexmedetomidine induces nearly complete sympatholysis already at low concentrations, and postsynaptic effects, such vasoconstriction, can be observed with increasing concentrations. Thus, local infusions of small doses of dexmedetomidine into dorsal hand veins and the application of pharmacological sympathectomy with brachial plexus block provide a means to assess drug-induced peripheral vascular responses without interference from systemic pharmacological effects and autonomic nervous system regulation. Dexmedetomidine was observed to have biphasic effects on haemodynamics, with an initial decrease in blood pressure at low concentrations followed by substantial increases in blood pressure and coronary vascular resistance at high concentrations. Plasma concentrations of dexmedetomidine that significantly exceeded the recommended therapeutic level did not reduce myocardial blood flow below the level that is observed with the usual therapeutic concentrations and did not induce any evident myocardial ischaemia in healthy subjects. Further, it was demonstrated that dexmedetomidine also had significant vasodilatory effects through activation of endothelial nitric oxide synthesis, and thus when the endothelial component of the blood vessel response to dexmedetomidine was inhibited, peripheral vasoconstriction was augmented. Hand vein constriction responses to α2-adrenoceptor activation by dexmedetomidine were only weakly associated with the constriction responses to α1-adrenoceptor activation, pointing to independent cellular regulation by these two adrenoceptor classes. Substantial inter-individual variation was noted in the venous constriction elicited by activation of α2-adrenoceptors by dexmedetomidine. In two study populations from two different continents, a single nucleotide polymorphism in the PRKCB gene was found to be associated with the dorsal hand vein constriction response to dexmedetomidine, suggesting that protein kinase C beta may have an important role in the vascular α2-adrenoceptor signalling pathways activated by dexmedetomidine.

Vammaisuus hyvinvointivaltiossa. Invalideiksi, vajaamielisiksi tai kehitysvammaisiksi määriteltyjen kansalaisasema suomalaisessa vammaispolitiikassa 1940-luvun taitteesta vuoteen 1987

Tutkimuksessa tarkastellaan vammaisiksi määriteltyjen ihmisten kansalaisasemaa suomalaisessa toisen maailmansodan jälkeisessä vammaispoliittisessa keskustelussa. Analyysissa huomioidaan suomalaisen vammaishuollon molemmista päälinjoista, eli invalidihuollosta sekä vajaamielis- ja kehitysvammahuollosta, käydyt keskustelut. Tutkimuksen aikarajauksena toimii niin kutsuttu invalihuollon kausi, joka ulottui lakisääteisen vammaishuollon tarpeesta 1940-luvun taitteessa virinneestä keskustelusta vuoteen 1987, jolloin säädettiin periaatteiltaan edeltävään lainsäädäntöön verrattuna uudenlainen laki vammaisuuden perusteella järjestettävistä palveluista ja tukitoimista. Vammaisuuden käsitettä lähestytään tutkimuksessa yhtenä modernin sosiaalipoliittisen lainsäädännön kategorioista, jotka ovat vapauttaneet kansalaisen velvollisuudesta itsensä ja perheensä elättämiseen ja oikeuttaneet hänet toimeentulossaan sosiaaliturvaan. Tutkimuksessa pyritään hahmottamaan millaiseksi tutkimuksen kohteena olevien vammaisten ryhmien kansalaisasema tutkimusajankohtana ymmärrettiin. Tarkastelussa keskitytään kansalaisuuden käsitteen niin kutsuttuun aineellisoikeudelliseen sisältöön analysoimalla tutkimuksen kohteena olevissa keskusteluissa esiintyneitä kansalaisuuden ideaaleja ja käsityksiä kansalaisen ja valtion suhteesta. Tutkimusaihetta lähestytään etsimällä vastausta kysymyksiin 1) Mihin yhteiskunnallisiin ongelmiin invalidihuollosta ja vajaamielis- tai 312 kehitysvammahuollosta käydyissä asiantuntijakeskusteluissa haettiin ratkaisuja? 2) Millaisia tavoitteita huollolle asetettiin? 3) Millaiseksi hahmotettiin huollon kohderyhmien asema ja tehtävät yhteiskunnassa? Analyysissa keskitytään huollosta käydyn asiantuntijakeskustelun tarkasteluun. Tutkimuksen keskeisin lähdeaineisto muodostuu tutkimusajankohdan vammaishuoltoa käsittelevästä lainsäädännöstä, sen valmistelun materiaaleista sekä vammaisjärjestöjen ja muiden alan asiantuntijoiden vammaishuollosta julkisuudessa käymästä keskustelusta. Tutkimuksessa esitetään, että suomalaisen vammaispolitiikan ja vammaisten kansalaisaseman kehityksessä on tutkimusajankohtana erotettavissa kolme vaihetta: 1) 1940–1950-lukujen yhteiskunnan rationalisointia ja sosiaalisten ongelmien vähentämistä painottaneella ennaltaehkäisevän huoltopolitiikan kaudella vammaiset ihmiset hahmotettiin yhteiskunnan reunamilla tai ulkopuolella olevaksi erityisryhmäksi, joka tuli pyrkiä huollon toimenpiteillä integroimaan omalle paikalleen yhteiskunnan kokonaisuuteen. 2) 1960-luvun kuntoutusideaalin laajenemisen kaudella vammaishuollon julkilausutuksi tavoitteeksi omaksuttiin yksilön edun ajaminen. 3) 1970–1980-lukujen normalisaation periaatetta painottaneessa vammaispolitiikassa tavoitteeksi otettiin vammaisille tarkoitettujen erityisjärjestelmien purkaminen sekä vammaisten tasa-arvoisen kansalaisaseman turvaaminen heidän osallistumismahdollisuuksiaan parantavilla tukitoimenpiteillä.

Genesis and Evolution of Brittle Structures In Southwestern Finland and Western South Africa. Insights into Fault Reactivation, Fluid Flow and Structural Maturity in Precambrian Cratons

The bedrock of old crystalline cratons is characteristically saturated with brittle structures formed during successive superimposed episodes of deformation and under varying stress regimes. As a result, the crust effectively deforms through the reactivation of pre-existing structures rather than by through the activation, or generation, of new ones, and is said to be in a state of 'structural maturity'. By combining data from Olkiluoto Island, southwestern Finland, which has been investigated as the potential site of a deep geological repository for high-level nuclear waste, with observations from southern Sweden, it can be concluded that the southern part of the Svecofennian shield had already attained structural maturity during the Mesoproterozoic era. This indicates that the phase of activation of the crust, i.e. the time interval during which new fractures were generated, was brief in comparison to the subsequent reactivation phase. Structural maturity of the bedrock was also attained relatively rapidly in Namaqualand, western South Africa, after the formation of first brittle structures during Neoproterozoic time. Subsequent brittle deformation in Namaqualand was controlled by the reactivation of pre-existing strike-slip faults.In such settings, seismic events are likely to occur through reactivation of pre-existing zones that are favourably oriented with respect to prevailing stresses. In Namaqualand, this is shown for present day seismicity by slip tendency analysis, and at Olkiluoto, for a Neoproterozoic earthquake reactivating a Mesoproterozoic fault. By combining detailed field observations with the results of paleostress inversions and relative and absolute time constraints, seven distinctm superimposed paleostress regimes have been recognized in the Olkiluoto region. From oldest to youngest these are: (1) NW-SE to NNW-SSE transpression, which prevailed soon after 1.75 Ga, when the crust had sufficiently cooled down to allow brittle deformation to occur. During this phase conjugate NNW-SSE and NE-SW striking strike-slip faults were active simultaneous with reactivation of SE-dipping low-angle shear zones and foliation planes. This was followed by (2) N-S to NE-SW transpression, which caused partial reactivation of structures formed in the first event; (3) NW-SE extension during the Gothian orogeny and at the time of rapakivi magmatism and intrusion of diabase dikes; (4) NE-SW transtension that occurred between 1.60 and 1.30 Ga and which also formed the NW-SE-trending Satakunta graben located some 20 km north of Olkiluoto. Greisen-type veins also formed during this phase. (5) NE-SW compression that postdates both the formation of the 1.56 Ga rapakivi granites and 1.27 Ga olivine diabases of the region; (6) E-W transpression during the early stages of the Mesoproterozoic Sveconorwegian orogeny and which also predated (7) almost coaxial E-W extension attributed to the collapse of the Sveconorwegian orogeny. The kinematic analysis of fracture systems in crystalline bedrock also provides a robust framework for evaluating fluid-rock interaction in the brittle regime; this is essential in assessment of bedrock integrity for numerous geo-engineering applications, including groundwater management, transient or permanent CO2 storage and site investigations for permanent waste disposal. Investigations at Olkiluoto revealed that fluid flow along fractures is coupled with low normal tractions due to in-situ stresses and thus deviates from the generally accepted critically stressed fracture concept, where fluid flow is concentrated on fractures on the verge of failure. The difference is linked to the shallow conditions of Olkiluoto - due to the low differential stresses inherent at shallow depths, fracture activation and fluid flow is controlled by dilation due to low normal tractions. At deeper settings, however, fluid flow is controlled by fracture criticality caused by large differential stress, which drives shear deformation instead of dilation.