A mouse model for improving cell survival of bisected cattle embryos

Selostus: Hiiren alkio mallina solukestävyyden parantamiseksi naudan alkioiden halkaisussa

Survival and early seedling growth of conifers with different shade tolerance in a Sitka spruce spacing trial and relationship to understorey light climate

Abstract

Pre-harvest soil acidification, liming or N fertilization did not significantly affect the survival and growth of young Norway spruce

Abstract

Survival-time analysis of white spruce during spruce budworm defoliation

Abstract

Operative Treatment of Ovarian Cancer and Borderline Tumors in Different Hospital Categories in Finland

Surgery is the cornerstone of ovarian cancer treatment and maximal cytoreduction is important. In the early 1980’s primary surgical treatment of ovarian cancer was performed in over 80 hospitals in Finland. The significance of the operative volume of the hospital, of the training of the surgeons and of centralization of surgical treatment has been widely discussed. The aim of the present study was to evaluate the outcome of surgical treatment of ovarian cancer in different hospital categories retrospectively and prospectively, and to analyze if any differences are reflected in survival. The retrospective study included 3851 ovarian cancer patients operated between 1983 and 1994 in Finland. The data was analyzed according to hospital category (university, central, and other) and by quartiles of the hospital operative volume. The results showed that patients operated in the highest operative volume hospitals had the best relative survival. When stratifying the analysis by the period of diagnosis (1983-1988 and 1989-1994), the university hospitals improved their performance the most. The prospective part of the thesis was initiated in 1999 and included 307 patients with invasive ovarian cancer and 65 patients with an ovarian borderline tumor. The baseline and 5-year surveys used a questionnaire that was filled in by the operating surgeons. For analysis of the 5-year followup data, the hospitals were divided into three categories (<10, 10-20, or >20 patients operated in 1999). The effect of the surgical volume was analyzed also as a continuous variable (1-47 operations per year). In university hospitals, pelvic lymphadenectomy was performed in 88 %, and para-aortic lymphadenectomy in 73 %, of the patients with stage I disease. The corresponding figures ranged from 11 % to 21 % in the other hospitals. For stage III ovarian cancer patients operated by gynecological oncologists, the estimated odds ratio for no macroscopic residual tumor was 3.0 times higher (95 % CI 1.2-7.5) than for those operated by general gynecologists. In the university and other hospitals 82% of the patients received platinum-based chemotherapy. Platinum + taxane combination was given to 63 % of the patients in the university and in 49 % in the other hospitals (p = 0.0763). Only a minority of the patients with tumors of borderline malignancy were staged according to recommendations, most often multiple peritoneal biopsies and omentectomy were neglected. FIGO stage, patient age, and residual tumor were independent prognostic factors of cancer-specific 5-year survival. A higher hospital operative volume was also a significant prognostic factor for better cancer-specific survival (p = 0.036) and disease-free survival (p = 0.048). In conclusion, ovarian cancer patients operated in high-volume university hospitals were more often optimally debulked and had a significantly better cancer-specific survival than patients operated in other hospitals. These results favor centralization of primary surgical treatment of ovarian cancer.

Survival and Quality of Life among Patients with Severe Lower Extremity Peripheral Arterial Disease

Lower extremity peripheral arterial disease (PAD) is associated with decreased functional status, diminished quality of life (QoL), amputation, myocardial infarction, stroke, and death. Nevertheless, public awareness of PAD as a morbid and mortal disease is low. The aim of this study was to assess the incidence of major lower extremity amputation due to PAD, the extent of reamputations, and survival after major lower extremity amputation (LEA) in a population based PAD patient cohort. Furthermore, the aim was to assess the functional capacity in patients with LEA, and the QoL after lower extremity revascularization and major amputation. All 210 amputees due to PAD in 1998–2002 and all 519 revascularized patients in 1998–2003 were explored. 59 amputees alive in 2004 were interviewed using a structured questionnaire of QoL. Two of each amputee age-, gender- and domicile-matched controls filled in and returned postal self-administered QoL questionnaire as well as 231 revascularized PAD patients (the amount of these patients who engaged themselves to the study), and one control person for each patient completed postal self-administered QoL questionnaire. The incidence rate of major LEA was 24.1/100 000 person-years and it was considerably high during the years studied. The one-month mortality rate was 21%, 52% at one-year, and the overall mortality rate was 80%. When comparing the one-year mortality risk of amputees, LEAs were associated with a 7.4-fold annual mortality risk compared with the reference population in Turku. Twenty-two patients (10%) had ipsilateral transversions from BK to AK amputation. Fifty patients (24%) ended up with a contralateral major LEA within two to four amputation operations. Three bilateral amputations were performed at the first major LEA operation. Of the 51 survivors returning home after their first major LEA, 36 (71%) received a prosthesis; (16/36, 44%) and were able to walk both in- and outdoors. Of the 68 patients who were discharged to institutional care, three (4%) had a prosthesis one year after LEA. Both amputees and revascularized patients had poor physical functioning and significantly more depressive symptoms than their controls. Depressive symptoms were more common in the institutionalized amputees than the home-dwelling amputees. The surviving amputees and their controls had similar life satisfaction. The amputees felt themselves satisfied and contented, whether or not they lived in long-term care or at home. PAD patients who had undergone revascularizations had poorer QoL than their controls. The revascularized patients’ responses on their perceived physical functioning gave an impression that these patients are in a declining life cycle and that revascularizations, even when successful, may not be sufficient to improve the overall function. It is possible that addressing rehabilitation issues earlier in the care may produce a more positive functional outcome. Depressive symptoms should be recognized and thoroughly considered at the same time the patients are recovering from their revascularization operation. Also primary care should develop proper follow-up, and community organizations should have exercise groups for those who are able to return home, since they very often live alone. In rehabilitation programs we should consider not only physical disability assessment but also QoL.

Superoxide dismutase 3-mediated cell survival and proliferation

This dissertation studies the signaling events mediated by the extracellular superoxide dismutase (SOD3). SOD3 is an antioxidant enzyme which converts the harmful superoxide into hydrogen peroxide. Overproduction of these reactive oxygen species (ROS) in the cellular environment as a result of tissue injury or impaired antioxidant defense system has detrimental effects on tissue integrity and function. However, especially hydrogen peroxide is also an important signaling agent. Ischemic injury in muscle causes acute oxidative stress and inflammation. We investigated the ability of SOD3 to attenuate ischemia induced inflammation and to promote recovery of skeletal muscle tissue. We found that SOD3 can downregulate the expression of several inflammatory cytokines and cell adhesion molecules thus preventing the accumulation of oxidant-producing inflammatory cells. Secondly, SOD3 was able to promote long-term activation of the mitogenic Erk pathway, but increased only briefly the activity of pro-survival Akt pathway at an early stage of ischemic inflammation, thus reducing apoptosis. SOD3 is a prominent antioxidant in the thyroid gland where oxidative stress is constantly present. We investigated the role of SOD3 in normal thyroid follicular cells and the changes in its expression in various hyperproliferative disorders. We first showed that SOD3 is TSH-responsive which indicated its participation in thyroid function. Its principal function seems to be in follicular cell proliferation since knockdown cells were deficient in proliferation. Additionally, it was overexpressed in goiter tissue. However, SOD3 was consistently downregulated in thyroid cancer cell lines and tissues. In conclusion, SOD3 is involved in tissue maintenance, cell proliferation and inflammatory cell migration. Its mechanisms of action are the activation of known proliferation/survival pathways, inhibition of apoptosis and regulation of adhesion molecule expression.