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  • Niemelä, Lotta (Helsingfors universitet, )
    Käsittelen pro gradu -tutkielmassani lomauttamisen vaikutusta työntekijän oikeuksiin ja velvollisuuksiin. Lisäksi selvitän millä edellytyksillä työntekijä voidaan lomauttaa, ja onko lomauttamisperusteen valinnalla merkitystä työntekijän lomautuksen aikaisen oikeudellisen aseman kannalta. Tutkielma kattaa työsopimuslain mukaisen lomauttamisen. Olen rajannut tutkielman ulkopuolelle valtion ja kunnan virkamiesten ja kirkon työntekijöiden lomauttamisen sekä luottamusmiehiä koskevan erityissääntelyn. Lomauttamisella tarkoitetaan työsopimuslain mukaan työnteon ja palkanmaksun väliaikaista keskeyttämistä. Lomauttamiselle tarvitaan työsopimuslain mukainen peruste, ja sen on tapahduttava työnantajan aloitteesta. Työntekijä voidaan lomauttaa joko taloudellisen ja tuotannollisen irtisanomisperusteen ollessa käsillä tai työn tai työntarjoamisedellytysten vähentyessä tilapäisesti. Lomauttamisesta voidaan myös tietyin edellytyksin sopia työsuhteen osapuolten välisillä sopimuksilla tai työehtosopimuksen määräyksillä. Lomauttaminen voidaan toimeenpanna toistaiseksi tai määräajaksi. Määräaikainen työntekijä voidaan työsopimuslain mukaan lomauttaa vain, jos hänet on palkattu vakituisen työntekijän sijaiseksi. Määräaikaisten työntekijöiden lomauttamiseen liittyy tiettyjä ongelmatilanteita, joita käsittelen tutkielmassani mahdollisimman kattavasti. Työsuhteesta aiheutuu sen osapuolille tiettyjä velvoitteita. Työntekijän pääasiallinen velvoite on tehdä työtä työnantajan lukuun. Työnantajan päävelvoite on puolestaan maksaa palkkaa tehdystä työstä. Työsopimuksen osapuolilla on näiden päävelvoitteiden lisäksi myös muita työsuhteesta johtuvia velvoitteita, nk. työsuhteesta aiheutuvia sivuvelvoitteita. Työntekijältä odotetaan tietynlaista lojaaliutta työnantajaansa kohtaan. Työoikeudessa tämä periaate tunnetaan työntekijän lojaliteettivelvollisuutena. Lojaliteettivelvollisuuden nimissä työntekijän tulee esimerkiksi pidättäytyä hyvän tavan vastaisesta kilpailusta työnantajan kanssa. Työntekijä ei saa paljastaa työnantajan liike- ja ammattisalaisuuksia eikä levittää työnantajasta perättömiä tietoja. Nämä velvollisuudet ovat tietyin poikkeuksin voimassa myös lomautusaikana. Työntekijä saa lomautuksen ajaksi ottaa muuta työtä turvatakseen elatuksensa. Selvitän tutkielmassani miten lomautuksen aikainen työllistyminen vaikuttaa työntekijän lojaliteettivelvollisuuteen. Lisäksi tarkastelen lomauttamisen vaikutusta työntekijän vuosiloman ansaintaan, palkan osana maksettaviin työsuhde-etuuksiin sekä työsuhteen päättymiseen. Käsittelen myös lyhyesti osa-aikaisesti lomautettujen työntekijöiden oikeusasemaa.
  • Väänänen, Hanna Emilia (2000)
    Tutkielmassa on tarkasteltu Lomé-sopimusjärjestelmän kauppapoliittisen ulottuvuuden tulevaisuutta Maailman kauppajärjestön luomassa uudessa kauppapoliittisessa tilanteessa. Lomé-sopimusjärjestelmä on toiminut vuodesta 1975 alkaen Euroopan unionin AKT-maihin suuntautuvan kehitysyhteistyön ja kauppapolitiikan viitoittajana. Merkittävä käännekohta tapahtui helmikuussa 2000 Lomé IV -yhteistyösopimuksen umpeutuessa. Tutkielman viitekehyksen muodostaa vapaakauppa, jota Maailman kauppajärjestö toteuttaa omien sääntöjen ja periaatteiden avulla. Vapaakauppa tutkimuksen viitekehyksenä antaa selkeän kuvan siitä minkälaisessa maailmassa teollisuusmaat ja kehitysmaat käyvät keskinäistä kauppaa ja minkälaiset säännöt ohjaavat maiden kauppasuhteita. Vaikka AKT-maista suurin osa on WTO:n jäseniä, ovat maiden mahdollisuudet hyödyntää vapaakaupan mahdollisuuksia ja etuja edelleen rajalliset. Uusittu Lomé-sopimusjärjestelmä luo uudet puitteet vapaakaupan etujen hyödyntämiseksi. Uudessa sopimusjärjestelmässä luodaan alueelliseen integraatioon perustuva vapaakauppajärjestelmä edesauttaen kehitysmaita kaupan esteiden purkamisessa ja rohkaisten kehitysmaita liittoutumaan keskenään sekä integroitumaan maailmankauppaan. Tutkielmassa esitetään kokonaisvaltainen kuvaus Lomé-sopimusjärjestelmästä ja Maailman kauppajärjestöstä uuden vuosituhannen kynnyksellä sekä tehdään tulevaisuutta koskeva analyysi uudistusten vaikutuksista AKT-maiden poliittiseen ja taloudelliseen toimintaan sekä AKT-maiden kauppasuhteisiin ja keskinäiseen kaupankäyntiin. Tutkimusongelmana tutkielmassa on Euroopan unionin ja AKT-maiden välisen Lomé-sopimusjärjestelmän kauppapoliittinen ulottuvuus, kauppapoliittisten järjestelyiden ristiriidat suhteessa Maailman kauppajärjestön sääntöihin ja periaatteisiin sekä arviot uudistetun sopimusjärjestelmän kauppapoliittisen ulottuvuuden vaikutuksista AKT-maiden taloudelliseen toimintaan. Tutkimustavoitteisiin on pyritty sekä tehtyjen haastatteluiden avulla että kuvailemalla Lomé-sopimusjärjestelmän ja WTO:n kehitystä lähdekirjallisuudesta ja haastatteluista saatujen tietojen avulla. Tutkielman empiirisen aineiston muodostaa kolme toukokuussa 2000 tehtyä vapaamuotoista haastattelua. Tutkielmaa varten haastateltiin Teollisuuden Työnantajien, Ulkoasiainministeriön sekä kansalaisjärjestöjen edustajia. Haastatteluiden avulla on pyritty selkeyttämään kuvaa siitä, miten uudistetut kauppapoliittiset järjestelyt tulevat mahdollisesti vaikuttamaan AKT-maiden taloudelliseen toimintaan sekä maiden mahdollisuuksiin pärjätä vapaassa maailmankaupassa. Tulevaisuutta koskeviin arvioihin on kuitenkin suhtauduttava varauksella, sillä uuden sopimusjärjestelmän kauppapoliittisten uudistusten vaikutukset AKT-maihin ovat varmuudella nähtävissä vasta vuosien kuluessa.
  • Vesama, Klaus (Helsingin yliopisto, 1999)
  • Aivelo, Tuomas (Helsingin yliopisto, 2015)
    Parasite community dynamics is one of the central themes in contemporary parasitology. While between-host dynamics has been studied for a long time, within-host dynamics is less well studied. My aim was to identify which factors affect the parasite community during the lifetime of individual hosts by following longitudinally several individuals from a long-living species. Specifically, I was interested in how the dynamics of infra- and component communities differ from one another and which traits explain the variation in infracommunities. I studied rufous mouse lemur (Microcebus rufus), which is a primate living in the eastern montane rainforests of Madagascar. Mouse lemur is a well-suited study species as it can live for up to ten years in the wild. Due to its small size, the population density is high and trapping straightforward. Nematodes are the most common helminths found in mouse lemurs, but their identification is difficult. Typically, the nematodes are identified from adult specimens, but for longitudinal studies, this is not possible, as we cannot dissect the host individuals. In addition, morphological differences between species are small and we expected to encounter previously undescribed species. These difficulties led to the development of a new method, based on metabarcoding, to identify parasitic nematodes from fecal samples. The method I developed encompasses all steps from fieldwork to sequence analysis. Despite numerous confounding factors, the method managed to amplify and analyze half of the samples collected. Whilst there is room for further improvements, the main advantage is that the method works well for different host species, for example mouse lemurs and gastropods. In principle, this method works for all species of nematode, including free-living soil nematodes. Nevertheless, the resolution of identification do not allow for species-level identification. The variation in the parasite community inside individual hosts was extensive, but at the population level remained stable. Most of the parasites belonged to the putative species thought to be Strongyloides sp. The reason for this species success might be its lifecycle, the parasite can live in the intestine or as a free-living form in the soil. Due to the limited number of samples, the factors affecting the dynamics in individual mouse lemurs are difficult to analyze. It appears that sex and age do not have an effect on either parasite load or variation in parasite dynamics. Nevertheless, body condition appears to bear a consequence with the individuals in better condition having more parasite species in addition to higher fecal egg loads. The reason may be that those individuals are able to sustain larger populations of parasites, or that they are more tolerant to parasites. Hibernation could lead to the extinction of the nematode community, whereas higher precipitation appeared to lead to higher prevalences. This work gives insights into the dynamics of parasite communities both at the host individual and population level. It highlights the need for longitudinal studies as parasite community dynamics in host individual-level cannot be inferred from the host population-level The method I have developed can be used to perform more efficient and faster surveys of previously unknown parasite communities, though further development is necessary for better reliability.
  • Ronkainen, Iina (2013)
    In this Master's thesis the long-term changes in Baltic Sea ice characteristics were studied. In the Baltic Sea the length of ice season is 5-7 months. The amount of seasonal ice varies significantly from year to year. However, in the last 100 years there has been a decreasing trend in the ice occurrence, which has resulted mainly from climate warming. Both observations and model results were analyzed in order to find out the long-term ice statistics, changes in ice conditions and reasons behind these changes. Three stations along the Finnish coast were chosen, Kemi in the Bay of Bothnia, Utö in the Archipelago Sea and Loviisa in the Gulf of Finland. The time series were 120 years long including the dates of freezing and break-up, the length of ice season and the maximum annual ice thickness. The model used was NEMO/LIM-3 and the modeled time 1961-2007. The key questions for the thesis were the positive trend in ice thickness in Kemi station, the reasons for the 100 year long decreasing trends although the climate warming has not affected so long and the changes in drift ice thickness. The study results show that the probability of ice occurrence has been decreasing in Utö and is now 81 %. In Kemi and Loviisa the probability is still 100 %. The freezing date has become 7-24 days later, while the break-up date has taken place 11-20 days earlier in 100 years. Consequently, the observed length of ice season has become 18-46 days shorter in 100 years. The trend of the maximum annual ice thickness is not so uniform. In Kemi station, there is an increasing trend, whereas in Loviisa the trend is decreasing. According to the model, the maximum annual ice thickness has a decreasing trend also in Kemi. The maximum annual ice volume has a decreasing trend in the entire Baltic Sea and also in different basins (Bay of Bothnia, Bothnian Sea and Gulf of Finland). The modeled ice volume correlates well with the observed maximum annual ice extent even though the ice volume has higher inter-annual variations. The possible other reasons besides rise in air temperature were detected. Sea ice thickness depends in addition to air temperature also greatly on snow accumulation and ice dynamics. The observation sites are not documented, so the places may have changed. The observation sites are usually near harbors and the increasing shipping might have affected ice conditions. The land uplift has been over 1 meter in Kemi during the 120 years, so that might also have an influence on results. In Loviisa the nuclear power plant might have affected the past few decades.
  • Åberg, Fredrik (Helsingin yliopisto, 2010)
    With transplant rejection rendered a minor concern and survival rates after liver transplantation (LT) steadily improving, long-term complications are attracting more attention. Current immunosuppressive therapies, together with other factors, are accompanied by considerable long-term toxicity, which clinically manifests as renal dysfunction, high risk for cardiovascular disease, and cancer. This thesis investigates the incidence, causes, and risk factors for such renal dysfunction, cardiovascular risk, and cancer after LT. Long-term effects of LT are further addressed by surveying the quality of life and employment status of LT recipients. The consecutive patients included had undergone LT at Helsinki University Hospital from 1982 onwards. Data regarding renal function – creatinine and estimated glomerular filtration rate (GFR) – were recorded before and repeatedly after LT in 396 patients. The presence of hypertension, dyslipidemia, diabetes, impaired fasting glucose, and overweight/obesity before and 5 years after LT was determined among 77 patients transplanted for acute liver failure. The entire cohort of LT patients (540 patients), including both children and adults, was linked with the Finnish Cancer Registry, and numbers of cancers observed were compared to site-specific expected numbers based on national cancer incidence rates stratified by age, gender, and calendar time. Health-related quality of life (HRQoL), measured by the 15D instrument, and employment status were surveyed among all adult patients alive in 2007 (401 patients). The response rate was 89%. Posttransplant cardiovascular risk factor prevalence and HRQoL were compared with that in the age- and gender-matched Finnish general population. The cumulative risk for chronic kidney disease increased from 10% at 5 years to 16% at 10 years following LT. GFR up to 10 years after LT could be predicted by the GFR at 1 year. In patients transplanted for chronic liver disease, a moderate correlation of pretransplant GFR with later GFR was also evident, whereas in acute liver failure patients after LT, even severe pretransplant renal dysfunction often recovered. By 5 years after LT, 71% of acute liver failure patients were receiving antihypertensive medications, 61% were exhibiting dyslipidemia, 10% were diabetic, 32% were overweight, and 13% obese. Compared with the general population, only hypertension displayed a significantly elevated prevalence among patients – 2.7-fold – whereas patients exhibited 30% less dyslipidemia and 71% less impaired fasting glucose. The cumulative incidence of cancer was 5% at 5 years and 13% at 10. Compared with the general population, patients were subject to a 2.6-fold cancer risk, with non-melanoma skin cancer (standardized incidence ratio, SIR, 38.5) and non-Hodgkin lymphoma (SIR 13.9) being the predominant malignancies. Non-Hodgkin lymphoma was associated with male gender, young age, and the immediate posttransplant period, whereas old age and antibody induction therapy raised skin-cancer risk. HRQoL deviated clinically unimportantly from the values in the general population, but significant deficits among patients were evident in some physical domains. HRQoL did not seem to decrease with longer follow-up. Although 87% of patients reported improved working capacity, data on return to working life showed marked age-dependency: Among patients aged less than 40 at LT, 70 to 80% returned to work, among those aged 40 to 50, 55%, and among those above 50, 15% to 28%. The most common cause for unemployment was early retirement before LT. Those patients employed exhibited better HRQoL than those unemployed. In conclusion, although renal impairment, hypertension, and cancer are evidently common after LT and increase with time, patients’ quality of life remains comparable with that of the general population.
  • Hiukka, Anne (Helsingin yliopisto, 2009)
    Background and aims. Diabetic dyslipidemia is a highly atherogenic triad of increased triglycerides, decreased HDL cholesterol, and small dense LDL. Fibrates have a beneficial effect on diabetic dyslipidemia, and they have reduced cardiovascular events in randomized trials. Fenofibrate has reduced albuminuria and markers of low-grade inflammation and endothelial dysfunction. The present studies were undertaken to characterize the alterations of VLDL and LDL subclasses and to investigate the binding of LDL to arterial wall in type 2 diabetes. Further purpose was to elucidate the effects of fenofibrate on several lipoprotein subclasses, augmentation index (AIx), carotid intima-media thickness (IMT), and renal function. Subjects. 239 type 2 diabetic subjects were recruited among participants of the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study at the Helsinki centre. The patients were randomized to fenofibrate (200mg/d) or placebo for 5 years. Additionally, a healthy control group (N = 93) was recruited. Results. VLDL1 triglycerides increased in similar proportion to total triglycerides in type 2 diabetic patients and control subjects. Despite the increase in total apoCIII levels, VLDL apoCIII was decreased in diabetic patients. Enrichment of LDL with apoCIII induced a small increase in binding of LDL to arterial wall proteoglycan. Intrinsic characteristics of diabetic LDL, rather than levels of apoCIII, were responsible for increased proteoglycan binding of diabetic LDL with high apoCIII. Fenofibrate reduced triglycerides, increased LDL size, and shifted HDL subclasses towards smaller particles with no change in levels of HDL cholesterol. High levels of homocysteine were associated with lower increase of HDL cholesterol and apoA-I during fenofibrate treatment. Long-term fenofibrate treatment did not improve IMT, AIx, inflammation, or endothelial function. Fenofibrate decreased creatinine clearance and estimated glomerular filtration rate. No effect on albuminuria was seen with fenofibrate. Instead, Cystatin C was increased during fenofibrate treatment. Conclusions. 1) Elevation of VLDL 1 triglycerides was the major determinant of plasma triglyceride concentration in control subjects and type 2 diabetic patients. 2) LDL with high apoCIII showed multiple atherogenic properties, that were only partially mediated by apoCIII per se in type 2 diabetes 3) Fenofibrate demonstrated no effect on surrogate markers of atherosclerosis. 4) Fenofibrate had no effect on albuminuria and the observed decrease in markers of renal function could complicate the clinical surveillance of the patients. 5) Fenofibrate can be used to treat severe hypertriglyceridemia or in combination therapy with statins, but not to increase HDL levels.
  • Huhtakangas, Justiina (Helsingfors universitet, 2011)
    Objective There is high case-fatality rate and loss of productive life-years related to aneurysmal subarachnoid hemorrhage (aSAH) but little data on long-term survival of SAH patients. We aim to evaluate long-term excess mortality and related risk factors after aSAH. Methods One year survivors (n=3080) after aSAH from Department of Neurosurgery in Helsinki between 1980 and 2007 were reviewed for this retrospective follow-up study. Follow-up started one year after SAH and continued until death or the end of 2008 (36 960 patient-years). Mortality and relative survival ratio (RSR) were compared with matched general population. Results After 20 years, survivors of aSAH showed 18% excess mortality compared to general population. Risk factors included: old age; poor preoperative clinical condition; conservative aneurysm treatment; multiple aneurysms; and unfavourable clinical outcome at 3 months. Conclusion Even after initially favourable recovery, patients with aSAH experience excess mortality in the long run. Cardiovascular and cerebrovascular diseases are prominent in this population.
  • Holma, Irina (Helsingin yliopisto, 2013)
    Major depressive disorder (MDD) is a commonly occurring and burdensome disorder and one of the most important mental disorders in terms of public health impact. By the year 2030 MDD is predicted to be the leading cause of functional disability and the major disease or injury burden followed by ischemic heart disease and road traffic accidents (WHO, 2004). Depression is not only highly prevalent but also often a chronic, recurrent and comorbid illness often co-occurring with anxiety, personality, substance use disorders, and smoking. Effective MDD treatments have been available for decades. However, only a realized treatment is useful for patients. This study investigated (1) the 5-year prevalence, duration and predictors of maintenance pharmacological treatment of MDD, (2) temporal patterns of pharmacological and psychosocial treatment attitudes and adherence, (3) predictors of a granted disability pension, and (4) long-term associations and covariation of smoking behavior and MDD with comorbid alcohol use disorder as a potential confounding factor. The investigated cohort consisted of psychiatric out- and inpatients (N=269) of the Vantaa Depression Study (VDS), a regionally representative, prospective and naturalistic follow-up study. Just over a half of patients with recurrent depression received maintenance pharmacotherapy, and below a fifth of the time indicated; this was predicted by a good adherence to pharmacotherapy in the acute phase. Most patients reported positive attitudes towards treatment, and good adherence. Employment predicted positive attitude and larger social network good adherence to pharmacotherapy. Cluster B personality disorder symptoms predicted a negative attitude and poor adherence, while cluster C symptoms predicted a positive attitude and living alone good adherence to psychosocial treatment. One-fifth were granted a disability pension within 5 years, which was predicted by higher age, introversion, subjective inability to work, larger proportion of time spent depressed, comorbid somatic disorders, and lack of vocational education. A third of MDD patients smoked regularly throughout the follow-up. Smoking patients differed from non-smoking patients with regard to several clinical characteristics (particularly alcohol use disorders) and personality factors (personality disorders and neuroticism), which may markedly confound research on the impact of smoking.
  • Mustonen, Ulla (2009)
    Avioerojen yleisyydestä huolimatta vanhempien eron vaikutuksia lasten aikuisuuden parisuhteeseen on jokseenkin vähän tutkittu. Tämän tutkimuksen tavoitteena oli tutkia parisuhteen laatua aikuisuudessa, 32-vuotiaana, henkilöillä, jotka olivat kokeneet vanhempien avioeron lapsuudessa alle 16-vuotiaana. Lisäksi tutkittiin avioeroperheistä ja ehjistä perheistä lähtöisin olevien eroja psykososiaalisissa resursseissa sekä resurssien roolia vanhempien avioeron ja parisuhteen yhteydessä. Tutkimuksessa tarkasteltiin myös sukupuolten välisiä eroja edellä mainituissa ilmiöissä. Työ pohjautui osin kognitiivis-kehitykselliseen malliin, jonka mukaan varhaisia läheisiä ihmissuhteita, kuten vanhempi-lapsi-suhdetta, koskevat representaatiot vaikuttavat myöhempiin läheisiin ihmissuhteisiin. Tutkimus perustui prospektiivisen seurantatutkimuksen aineistoon, joka muodostui peruskoulun yhdeksäsluokkalaisille tamperelaisnuorille ja samoille henkilöille 32-vuotiaana tehdystä kyselyaineistosta. Lapsuudessa vanhempien avioeron kokeneet (naiset, n = 148, miehet, n = 102) ja ei-kokeneet (naiset, n = 498, miehet, n = 395) muodostivat vertailtavat ryhmät. Parisuhteen laatu aikuisuudessa käsitti henkilön oman arvion parisuhteesta, sen läheisyydestä ja ongelmallisuudesta. Psykososiaalisia resursseja tarkasteltiin 16-vuotiaana äiti- ja isäsuhteen läheisyydellä ja 32-vuotiaana itsetunnolla, tyytyväisyydellä sosiaaliseen tukeen ja coping -strategioilla (kognitiivinen, emotionaalinen, sosiaalisen tuen hakemiseen ja ongelmanratkaisuun keskittyvä). Analyysimenetelminä käytettiin pääasiassa yksisuuntaista varianssianalyysiä, hierarkkista regressioanalyysiä ja mediaatio -testiä. Tulokset osoittivat, että vanhempien eron lapsuudessa kokeneet olivat useammin eronneet tai asuivat asumuserossa 32-vuotiaana kuin ehjistä perheistä lähtöisin olevat. Vanhempien ero heikensi koettua parisuhteen laatua vain naisilla. Myös psykososiaalisten resurssien ja vanhempien avioeron yhteys todettiin vain naisilla. Heillä oli heikompi itsetunto ja he olivat tyytymättömämpiä sosiaaliseen tukeen 32-vuotiaana kuin ehjistä perheistä lähtöisin olevat naiset. Perhetaustasta riippumatta miehillä oli parempi itsetunto ja läheisempi suhde sekä äitiin että isään. Vaikka psykososiaaliset resurssit osittain välittivät vanhempien avioeron vaikutusta parisuhteen laatuun, vanhempien avioeron itsenäinen vaikutus parisuhteen laatuun säilyi merkitsevänä myös sen jälkeen, kun kaikki resurssit oli otettu huomioon. Tutkituista resursseista vain kognitiiviset coping-keinot suojasivat naisia vanhempien eron negatiivisilta vaikutuksilta parisuhteeseen. Tutkimus osoitti erityisesti tyttöjen haavoittuvuuden vanhempien avioeroprosessissa. Tarvittaessa tyttöjen itsetuntoa ja hyvää suhdetta molempiin vanhempiin tulisi tukea eri keinoin. Parisuhteen kriisissä tulisi ottaa huomioon lapsuuden perhetausta ja puolisoiden ongelmanratkaisutaidot ja tukea sopivien selviytymiskeinojen käytössä.
  • Tainio, Juuso (Helsingin yliopisto, 2015)
    Renal transplantation (RTx) has become an established treatment modality for end-stage renal disease in children. Along with the improvements in pre- and post-transplant care, the patient and graft outcomes have improved significantly during the past two decades. This attracts more attention to avoiding secondary complications and long-term side effects of the post-RTx immunosuppressive medication. Several risk factors cast a shadow over patients normal physical and mental development, but detailed reports on long-term outcome after pediatric RTx are scarce. This thesis was designed to investigate pubertal development and subsequent male fertility and semen quality with special emphasis on the effects of immunosuppressive medication on reproductive function. The study also aimed to analyze the prevalence of metabolic syndrome and its components in pediatric RTx patients and the association of these parameters with the long-term graft function. The onset of pubertal development occurred at the mean age of 12.7 years in boys with 22% considered delayed. In girls, however, no delayed development occurred, with the age at onset of puberty and menarche averaging 10.7 years and 12.5 years, respectively. Pubertal growth continued relatively long resulting in average final height of -1.7 height standard deviation score in boys and -1.2 in girls. The reproductive hormone levels were normal in a great majority of the patients. In young adult males who had received RTx in childhood, the free testosterone levels were lower and luteinizing hormone levels were higher in comparison with age-matched healthy controls. The RTx patients had also smaller testicular volumes and total sperm counts than the controls. Only a quarter of the RTx men who provided a semen sample had normospermia. Patients with a history of cyclophosphamide therapy had the worst outcome. Metabolic data were collected at several time points during a 13-year follow-up post-RTx. Hypertriglyceridemia associated with a worse kidney graft function at 1.5 and 5 years post-RTx, and it predicted the subsequent rate of kidney function decrease after 1.5 years post-RTx. Beyond the first postoperative year, other metabolic risk factors associated modestly with the long-term kidney graft function in pediatric RTx patients. The ambulatory BP monitoring data were retrospectively analyzed 5 to 10 years post-transplantation. The BP profiles were similar between renal, heart, and liver transplant groups. Hypertension was common especially at nighttime and the nocturnal BP dipping was often blunted. The use of antihypertensive medication did not notably change the ambulatory BP profile in RTx recipients. The BP variables correlated poorly with the metabolic parameters or kidney graft function.
  • Wedenoja, Satu (Helsingin yliopisto, 2007)
    The rare autosomal recessive disease congenital chloride diarrhea (CLD) is caused by mutations in the solute carrier family 26 member 3 (SLC26A3) gene on chromosome 7q22.3-31.1. SLC26A3 encodes for an apical epithelial chloride-bicarbonate exchanger, the intestinal loss of which leads to profuse chloride-rich diarrhea, and a tendency to hypochloremic and hypokalemic metabolic alkalosis. Although untreated CLD is usually lethal in early infancy, the development of salt substitution therapy with NaCl and KCl in the late 1960s made the disease treatable. While the salt substitution allows normal childhood growth and development in CLD, data on long-term outcome have remained unclarified. One of the world s highest incidences of CLD 1:30 000 to 1:40 000 occurs in Finland, and CLD is part of the Finnish disease heritage. We utilized a unique sample of Finnish patients to characterize the long-term outcome of CLD. Another purpose of this study was to search for novel manifestations of CLD based on the extraintestinal expression of the SLC26A3 gene. This study on a sample of 36 patients (ages 10-38) shows that the long-term outcome of treated CLD is favorable. In untreated or poorly treated cases, however, chronic contraction and metabolic imbalance may lead to renal injury and even to renal transplantation. Our results demonstrate a low-level expression of SLC26A3 in the human kidney. Although SLC26A3 may play a minor role in homeostasis, post-transplant recurrence of renal changes shows the unlikelihood of direct transporter modulation in the pathogenesis of CLD-related renal injury. Options to resolve the diarrheal symptoms of CLD have been limited. Unfortunately, our pilot trial indicated the inefficacy of oral butyrate as well. This study reveals novel manifestations of CLD. These include an increased risk for hyperuricemia, inguinal hernias, and probably for intestinal inflammation. The most notable finding of this study is CLD-associated male subfertility. This involves a low concentration of poorly motile spermatozoa with abnormal morphology, high seminal plasma chloride with a low pH, and a tendency to form spermatoceles. That SLC26A3 immunoexpression appeared at multiple sites of the male reproductive tract in part together with the main interacting proteins cystic fibrosis transmembrane conductance regulator (CFTR) and sodium-hydrogen exchanger 3 (NHE3) suggests novel sites for the cooperation of these proteins. As evidence of the cooperation, defects occurring in any of these transporters are associated with reduced male fertility. Together with a finding of high sweat chloride in CLD, this study provides novel data on extraintestinal actions of the SLC26A3 gene both in the male reproductive tract and in the sweat gland. These results provide the basis for future studies regarding the role of SLC26A3 in different tissues, especially in the male reproductive tract. Fortunately, normal spermatogenesis in CLD is likely to make artificial reproductive technologies to treat infertility and even make unassisted reproduction possible.
  • Mölsä, Sari (Helsingin yliopisto, 2014)
    Cranial cruciate ligament (CCL) disease is one of the most common causes of lameness in dogs. Surgical treatment is recommended to stabilize the stifle joint, alleviate pain, and delay the progression of osteoarthritis (OA). A variety of surgical techniques has been introduced and can be broken down into the more traditional intracapsular ligament replacement and extracapsular suture techniques and the newer neutralizing dynamic osteotomy techniques. Although an enormous amount of literature is available concerning this disease, surprisingly few studies have assessed surgical outcome with objective evaluation methods and comparison between groups. Previous studies have demonstrated significant improvement of limb function after CCL surgery. However, OA has been shown to progress in most patients, and this may cause deterioration in the function of the surgically treated limb over time. Long-term follow-up studies that include objective evaluation methods designed for assessing orthopedic outcome are needed. This thesis aimed to evaluate the long-term surgical outcome and signs of chronic pain after CCL surgery. Also, outcomes between the intracapsular, extracapsular and osteotomy techniques were compared. A multimodal approach, including an owner questionnaire and assessment of chronic pain using the validated Helsinki Chronic Pain Index (HCPI), orthopedic and radiographic examinations, force plate analysis, and as a new evaluation method, a physiotherapeutic examination was included. To provide reference values, clinically healthy Rottweilers and Labrador Retrievers were examined. A long-term retrospective follow-up with a mean time interval of at least 2.7 years between the surgery and evaluation was conducted. Of the 206 surgically treated dogs that were evaluated by their owners, 31.1% had a HCPI value ≥ 12, indicating pain. Of the 47 dogs evaluated by a veterinarian 31.9% showed a pain response to flexion/extension of the surgically treated joint. In addition to the unilaterally treated CCL rupture, contralateral stifle joint pathology and other orthopedic problems were frequently diagnosed during the evaluation. When symmetry of weight bearing was evaluated in dogs with no other orthopedic findings (n=21),approximately 30% of dogs had decreased dynamic and static weight bearing in the surgically treated limbs. Also, goniometric angles of the surgically treated limbs remained inferior to those of healthy limbs, and impairment of active range of motion was frequently observed. The owner assessments revealed no significant differences between the surgical techniques in long-term outcome. However, differences were seen in clinical evaluation of dynamic and static weight bearing between intracapsular and osteotomy technique groups. Although the retrospective study design and low sample size have to be acknowledged and may cause bias to the results, osteotomy techniques may offer long-term limb function that is superior to that achieved with the intracapsular technique. The low number of dogs treated with the extracapsular technique did not allow comparison of dynamic or static weight bearing to other technique groups.
  • Riihimäki, Kirsi (Helsingin yliopisto, 2014)
    This study is the first naturalistic prospective long-term follow-up with a life-chart among primary care patients with depressive disorders. Patients with lifetime MDD spent 34% of follow-up time in MDEs, 24% in partial and only 42% in full remission. Nine in ten achieved at least partial and two-thirds full remission. Baseline severity of depression and substance use comorbidity predicted time spent in MDEs: a rise in Hamilton Rating Scale for Depression (HAMD) score of ten at baseline predicted 14 months and comorbid substance use disorder 25 months more time in MDEs. One-half of those who achieved partial remission and one-third of those who reached full remission were having at least one recurrence. The recurrences were predicted by personality disorders. The time from remission to recurrence was predicted by generalized anxiety disorder and somatoform disorder. One-tenth of patients attempted suicide one to three times. The incidence rate varied robustly depending on the level of depression, being 0 per 1000 patient-years during full remission, 5.8 during partial remission and 107 during MDEs. Functional and work ability were strongly associated with duration and severity of depression. Patients who belonged to the labour force spent one-third of the follow-up off work due to depression; two-thirds were granted sick leave, and one-tenth a disability pension due to depression. Longer duration of depression, comorbid disorders and having received social assistance predicted dropping out from work. A quarter of patients suffered from concurrent borderline personality disorder (BPD). Comorbid anxiety and substance use disorders were common among them. Concurrent BPD increased the severity and duration of depression, suicidal behaviour, unemployment and economic difficulties. This study revealed often slow and incomplete recovery and a common recurrent course, which needs to be taken into account when developing services. The use of measurement scales is warranted when planning and monitoring treatment. Comorbidity, concurrent substance use disorder, anxiety disorders, somatoform disorder and BPD all need to be taken into account in clinical practice guidelines. Duration of depression appears most decisive for suicide attempts among primary care patients with depression. Efforts should focus on the continuity of care.
  • Holma, Mikael (Helsingin yliopisto, 2010)
    Much of what we know regarding the long-term course and outcome of major depressive disorder (MDD) is based on studies of mostly inpatient tertiary level cohorts and samples predating the era of the current antidepressants and the use of maintenance therapies. In addition, there is a lack of studies investigating the comprehensive significance of comorbid axis I and II disorders on the outcome of MDD. The present study forms a part of the Vantaa Depression Study (VDS), a regionally representative prospective and naturalistic cohort study of 269 secondary-level care psychiatric out- and inpatients (aged 20-59) with a new episode of DSM-IV MDD, and followed-up up to five years (n=182) with a life-chart and semistructured interviews. The aim was to investigate the long-term outcome of MDD and risk factors for poor recovery, recurrences, suicidal attempts and diagnostic switch to bipolar disorder, and the association of a family history of different psychiatric disorders on the outcome. The effects of comorbid disorders together with various other predictors from different domains on the outcome were comprehensively investigated. According to this study, the long-term outcome of MDD appears to be more variable when its outcome is investigated among modern, community-treated, secondary-care outpatients compared to previous mostly inpatient studies. MDD was also highly recurrent in these settings, but the recurrent episodes seemed shorter, and the outcome was unlikely to be uniformly chronic. Higher severity of MDD predicted significantly the number of recurrences and longer time spent ill. In addition, longer episode duration, comorbid dysthymic disorder, cluster C personality disorders and social phobia predicted a worse outcome. The incidence rate of suicide attempts varied robustly de¬pending on the level of depression, being 21-fold during major depressive episodes (MDEs), and 4-fold during partial remission compared to periods of full remission. Although a history of previous attempts and poor social support also indicated risk, time spent depressed was the central factor determining overall long-term risk. Switch to bipolar disorder occurred mainly to type II, earlier to type I, and more gradually over time to type II. Higher severity of MDD, comorbid social phobia, obsessive compulsive disorder, and cluster B personality disorder features predicted the diagnostic switch. The majority of patients were also likely to have positive family histories not exclusively of mood, but also of other mental disorders. Having a positive family history of severe mental disorders was likely to be clinically associated with a significantly more adverse outcome.
  • Tiippana-Kinnunen, Tarja (Helsingin yliopisto, 2014)
    This 15-year follow-up focused on radiographic outcome, functional capacity, work disability and comorbidity in 86 patients (age 18-65 years), with early (≤ 12 months of disease duration) rheumatoid arthritis (RA) collected in 1986-1989 in Helsinki area and treated with early initiated DMARD therapy. The outcome was determined in relation to DMARD continuity, early disease activity, early radiographic remission (ERR) and baseline comorbidity. Of the 70 patients evaluated at 15-year examination, 50 (71%) needed continuous DMARD therapy (group A). In 20 patients (29%) DMARDs were discontinued due to clinical remission. Of these disease flared up and DMARDs were reintroduced in 9 patients (45%, group B) and 11 (55%) remained in remission (group C). The 15-year outcome was most favourable in group C: 64% of patients being in remission, according to American Collage of Rheumatology criteria, compared with 0% in B and 6% in A. Final functional capacity [mean Health Assessment Questionnaire (HAQ)] was 0.24 in C, 0.38 in B and 0.60 in A and radiographic outcome assessed with mean Larsen score (LS) 12, 25 and 54, respectively. As conclusion, patients whose DMARDs are discontinued due to remission, should be followed up closely for a flare-up of the disease. For those whose disease flares up, DMARDs should be reintroduced immediately. The 15-year LS of 69 patients determined in relation to ERR [an increase of LS ≤ 1 Larsen unit (LU) between two sequential sets of small joint radiographs during the first 2 years]. Mean 15-year LS of the small joints (14) and LS of the large joints (0.8) were lower in patients with sustained ERR (both year 1 and year 2), compared with 33 and 1.9 in patients with temporary ERR (either year 1 or year 2) or with 67 and 6.3 in patients with radiographic progression ≥ 2 LU during both first years. Considering these findings, radiographic remission should be a treatment goal in RA and early progression in small joints should be taken as a warning sign for later damage of large joints. Of 80 patients with adequate data, 20% had at least one comorbid condition at baseline and 60 % had comorbidities at the 15-year visit or at time od death, most commonly hypertension (30%), cardiovascular diseases (14%), malignancies (11%) or osteoporosis (11%). Elderly patients with baseline comorbidity showed higher disease activity both during first year of RA and at endpoint than younger patients without comorbidities. Of the 86 patients, 42 (49%) retired due to work disability (WD) during 15 years or before death, most of these due to RA. The Kaplan-Meier estimated cumulative RA-related WD was less frequent in patients with low disease activity during first 12 months (3% at year 5, 10% at year 10 and 22% at year 15) than in those with moderate or high disease activity (28%, 55% and 64%, respectively). The results of this study showed that most patients with RA need continuous DMARD treatment and emphasize the importance of targeting to clinical remission and to radiographic remission in early phase of the disease for the long-term outcome in RA.
  • Pelttari, Hanna (Helsingin yliopisto, 2012)
    The goal of initial therapy in differentiated thyroid cancer (DTC) is to minimize disease related mortality and morbidity by surgically removing the primary tumour and all metastasized tumour tissue. A second goal is to minimize risk of recurrence and metastatic spread by facilitating post-operative radio-iodine ablation (RRA), permitting accurate long-term surveillance. Recurrences are relatively common even in patient population at low-risk for cancer-specific death, occurring in 10-40% of cases. The treatment and follow-up schemes have varied between centres and there is ongoing debate about appropriate methods for primary therapy and surveillance. With the increasing incidence of DTC, the need for new factors prognostic of disease recurrence is growing; most of the prognostic systems have been validated with cancer-specific death as outcome. We designed an observational retrospective study to assess the outcome of a large cohort of patients with low-risk thyroid carcinoma and with a uniform primary therapy. All patients belong to TNM stage I or II and were considered disease-free after initial therapy. We evaluated the safety and efficacy of a surveillance paradigm, comprising yearly thyroglobulin (TG) measurements on L-T4 therapy and neck ultrasonography (US) every second year, with an increase in TG to a detectable level being an indication for further investigations. We examined the health-related quality of life (HRQoL) of the patient cohort after long-term follow-up using a validated multidimensional method (15D®). We studied factors correlating with disease recurrence, including patient demographics, tumour characteristics and parameters with primary therapy, in 495 low-risk patients treated at Helsinki University Central Hospital over a 15-year period. Post-operative and post-ablative TG concentrations, age, tumour size, local infiltration and nodal metastasis at primary surgery, number of neck US, fine-needle aspiration biopsies (FNABs) and operations performed, presence of BRAF mutation in papillary tumour tissue, disease recurrences and cancer-specific deaths were evaluated. The majority of patients had total thyroidectomy and radio-active iodine remnant ablation as initial treatment. The median follow-up was 16 (range 10 24) years. Fifty-one patients (10.3%) experienced disease recurrence during follow-up. A combination of neck US and high TG revealed most recurrences. In multiple logistic regression analysis, post-ablative measurable TG concentrations (odds ratio (OR) 3.72, confidence interval (CI) 1.71 8.05, P = 0.0009) and presence of local infiltration on primary surgery (OR 2.66, CI 1.03 6.90, P = 0.04) were the only independent predictors of recurrence. BRAF V600E mutation is common (prevalence 67%) in this low-risk papillary thyroid cancer patient group but does not predict recurrence after long-term follow-up after initial treatment with total thyroidectomy (TTE) and RRA. HRQoL was preserved in DTC patients compared to a large age- and gender-standardized sample of the general Finnish population (n = 6001). After long-term follow-up, overall HRQoL is comparable with that of the general population. DTC patients demonstrate an age-related decline in HRQoL, similar to that seen in the population in general. We conclude that post-ablative TG concentration is a strong predictor of disease recurrence in DTC. Although longer follow-up is needed, monitoring low-risk differentiated thyroid carcinoma patients with neck US and TG measured on L-T4 appears safe and effective.The same principles have now been adapted also by many international centres.