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Sökning: WFRF:(Andersen Marianne)

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  • Bengtsson, D., et al. (författare)
  • Long-Term Outcome and MGMT as a Predictive Marker in 24 Patients With Atypical Pituitary Adenomas and Pituitary Carcinomas Given Treatment With Temozolomide
  • 2015
  • Ingår i: Journal of Clinical Endocrinology & Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 100:4, s. 1689-1698
  • Tidskriftsartikel (refereegranskat)abstract
    • Context/Objective: Locally aggressive pituitary tumors (LAPT) and pituitary carcinomas respond poorly to conventional therapy and cytotoxic drugs. Temozolomide (TMZ) is an oral alkylating drug with good tolerability, approved for treatment of malignant gliomas. The experience of its use in pituitary tumors is limited. Design and Setting: We report on 24 patients with aggressive pituitary tumors (16 LAPTs, 8 carcinomas) treated with TMZ for a median of 6 months (range 1-23). Follow-up ranged from 4 to 91 months with a median of 32.5 months. 19/24 tumors were hormone secreting (PRL 9, ACTH 4, GH 4, GH/PRL 2). Ki-67 was 2-50% in LAPTs, and 5-80% in carcinomas. Main Outcome: Response to TMZ and the association with tumor expression of O6-methylguanine DNA methyltransferase (MGMT), MLH1, MSH2, and MSH6, examined by immunohistochemistry. Results: Complete tumor regression occurred in two carcinomas and persisted at follow-up after 48 and 91 months, respectively. Partial regress of tumor mass ranging from 35% to 80% occurred in 5 LAPTs and 2 carcinomas. Another patient with LAPT had a 71% decrease in prolactin levels without change in tumor volume. Three LAPTs could not be evaluated. Median MGMT staining was 9% (5-20%) in responders vs 93% (50-100%) in nonresponders. Loss of MSH2 and MSH 6 was observed in a single patient who had a rapid development of resistance to TMZ. Conclusions: This study shows that TMZ is a valuable treatment option for patients with uncontrolled pituitary tumors. The data suggest that tumoral MGMT staining below 50% is associated with a high likelihood of treatment response.
  • Ejlertsen, Bent, et al. (författare)
  • Improved outcome from substituting methotrexate with epirubicin : results from a randomised comparison of CMF versus CEF in patients with primary breast cancer
  • 2007
  • Ingår i: European Journal of Cancer. - 0959-8049 .- 1879-0852. ; 43:5, s. 877-884
  • Tidskriftsartikel (refereegranskat)abstract
    • We compared the efficacy of CEF (cyclophosphamide, epirubicin, and fluorouracil) against CMF (cyclophosphamide, methotrexate, and fluorouracil) in moderate or high risk breast cancer patients. We randomly assigned 1224 patients with completely resected unilateral breast cancer to receive nine cycles of three-weekly intravenous CMF or CEF. Patients were encouraged to take part in a parallel trial comparing oral pamidronate 150 mg twice daily for 4 years versus control (data not shown). Substitution of methotrexate with epirubicin significantly reduced the unadjusted hazard for disease-free survival (DFS) by 16% (hazard ratio 0.84; 95% CI; 0.71-0.99) and for overall survival by 21% (hazard ratio 0.79; 95% CI; 0.66-0.94). The risk of secondary leukaemia and congestive heart failure was similar in the two groups. Overall CEF was superior over CMF in terms of DFS and OS in patients with operable breast cancer without subsequent increase in late toxicities.
  • Andersen, Felicie F., et al. (författare)
  • Assembly and structural analysis of a covalently closed nano-scale DNA cage
  • 2008
  • Ingår i: Nucleic Acids Research. - 0305-1048 .- 1362-4962. ; 36:4, s. 1113-1119
  • Tidskriftsartikel (refereegranskat)abstract
    • The inherent properties of DNA as a stable polymer with unique affinity for partner mols. detd. by the specific Watson-Crick base pairing makes it an ideal component in self-assembling structures. This has been exploited for decades in the design of a variety of artificial substrates for investigations of DNA-interacting enzymes. More recently, strategies for synthesis of more complex two-dimensional (2D) and 3D DNA structures have emerged. However, the building of such structures is still in progress and more experiences from different research groups and different fields of expertise are necessary before complex DNA structures can be routinely designed for the use in basal science and/or biotechnol. Here we present the design, construction and structural anal. of a covalently closed and stable 3D DNA structure with the connectivity of an octahedron, as defined by the double-stranded DNA helixes that assembles from eight oligonucleotides with a yield of .apprx.30%. As demonstrated by Small Angle X-ray Scattering and cryo-Transmission Electron Microscopy analyses the eight-stranded DNA structure has a central cavity larger than the apertures in the surrounding DNA lattice and can be described as a nano-scale DNA cage, Hence, in theory it could hold proteins or other bio-mols. to enable their investigation in certain harmful environments or even allow their organization into higher order structures.
  • Ekberg, J., et al. (författare)
  • Design of an online health-promoting community : Negotiating user community needs with public health goals and service capabilities
  • 2013
  • Ingår i: BMC Health Services Research. - : BioMed Central. - 1472-6963 .- 1472-6963. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: An online health-promoting community (OHPC) has the potential to promote health and advance new means of dialogue between public health representatives and the general public. The aim of this study was to examine what aspects of an OHPC that are critical for satisfying the needs of the user community and public health goals and service capabilities.Methods: Community-based participatory research methods were used for data collection and analysis, and participatory design principles to develop a case study OHPC for adolescents. Qualitative data from adolescents on health appraisals and perspectives on health information were collected in a Swedish health service region and classified into categories of user health information exchange needs. A composite design rationale for the OHPC was completed by linking the identified user needs, user-derived requirements, and technical and organizational systems solutions. Conflicts between end-user requirements and organizational goals and resources were identified.Results: The most prominent health information needs were associated to food, exercise, and well-being. The assessment of the design rationale document and prototype in light of the regional public health goals and service capabilities showed that compromises were needed to resolve conflicts involving the management of organizational resources and responsibilities. The users wanted to discuss health issues with health experts having little time to set aside to the OHPC and it was unclear who should set the norms for the online discussions.Conclusions: OHPCs can be designed to satisfy both the needs of user communities and public health goals and service capabilities. Compromises are needed to resolve conflicts between users' needs to discuss health issues with domain experts and the management of resources and responsibilities in public health organizations.
  • Kristensen, Bent, et al. (författare)
  • Bisphosphonate treatment in primary breast cancer : Results from a randomised comparison of oral pamidronate versus no pamidronate in patients with primary breast cancer
  • 2008
  • Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 47:4, s. 740-746
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose and patients. During the period from January 1990 to January 1996 a total of 953 patients with lymph node negative primary breast cancer were randomised to oral pamidronate (n=460) 150 mg twice daily for 4 years or no adjuvant pamidronate (n=493) in order to investigate whether oral pamidronate can prevent the occurrence of bone metastases and fractures. The patients received adjuvant chemotherapy, loco-regional radiation therapy, but no endocrine treatment. Results. During the follow-up period the number of patients with pure bone metastases was 35 in the control group and 31 in the pamidronate group. The number of patients with a combination of bone and other distant metastases were 22 in the control group and 20 in the pamidronate group. The hazard rate ratio for recurrence in bone in the pamidronate group compared to the control group was 1.03 (95% confidence interval 0.75-1.40) and p=0.86. No effect was observed on overall survival. In a small subgroup of 27 patients from the study, 12 of whom were treated with pamidronate a significant bone preserving effect was observed on bone mineral density in the lumbar spine, but not in the proximal femur. Conclusion. The results from the trial do not support a beneficial effect of oral pamidronate on the occurrence of bone metastases or fractures in patients with primary breast cancer receiving adjuvant chemotherapy. © 2008 Taylor & Francis.
  • Kvorning, T, et al. (författare)
  • The activity of satellite cells and myonuclei following 8 weeks of strength training in young men with suppressed testosterone levels
  • 2015
  • Ingår i: Acta Physiologica. - 1748-1708 .- 1748-1716. ; 213:3
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To investigate how suppression of endogenous testosterone during an 8-week strength training period influences the activity of satellite cells and myonuclei.METHODS: Twenty-two moderately trained young men participated in this randomized, placebo-controlled, and double-blinded intervention study. The participants were randomized to treatment with a GnRH analogue, goserelin (n = 12), which suppresses testosterone or placebo (n = 10) for 12 weeks. The strength training period of 8 weeks started after 4 weeks of treatment and included exercises for all major muscles. Biopsies were obtained from the mid-portion of the vastus lateralis muscle.RESULTS: Testosterone resting level in goserelin was 10-20 times lower compared with placebo, and the training-induced increase in the level of testosterone was abolished in goserelin. Training increased satellite cells number in type II fibres by 20% in placebo and by 52% in goserelin (P < 0.01), whereas the myonuclear number significantly increased by 12% in type II fibres in placebo and remained unchanged in goserelin (P < 0.05). No changes in satellite cells and myonuclei were seen in type I fibres in either group. Data from the microarray analysis indicated that low testosterone affects the bone morphogenetic proteins signalling, which might regulate proliferation vs. differentiation of satellite cells.CONCLUSION: Eight weeks of strength training enhances the myonuclear number in type II fibres, and this is largely blocked by the suppression of testosterone. The data indicate that low testosterone levels could reduce the differentiation of satellite cells to myonuclei via the bone morphogenetic proteins signalling pathway, resulting in reduced increases in lean leg mass.
  • Pelanis, Rasa, et al. (författare)
  • The prevalence of Type 2 diabetes is not increased in normal-weight women with PCOS
  • 2017
  • Ingår i: ; 32:11, s. 2279-2286
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY QUESTION: Is oral glucose tolerance test (OGTT) needed in all women with polycystic ovary syndrome (PCOS)? SUMMARY QNSWER: OGTT is not routinely needed in women with PCOS and BMI < 25 kg/m(2). WHAT IS KNOWN ALREADY: PCOS is associated with insulin resistance and increased prevalence of prediabetes and Type 2 diabetes (T2D) which is closely linked to obesity and possibly age, ethnicity and PCOS phenotype. Several guidelines recommend OGTT upon diagnosis of PCOS and during follow-up. STUDY DESIGN, SIZE, DURATION: A Nordic cross-sectional study including 876 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 876 Nordic women with PCOS, aged 14-57 years, were examined for T2D and prediabetes (impaired glucose tolerance [IGT] or impaired fasting glucose (IFG) by OGTT. MAIN RESULT AND THE ROLE OF CHANCE: Of all study subjects 3% (23/876) had T2D, 23% (204/876) prediabetes and 74% (649/876) had normal glucose tolerance (NGT). Increased BMI and waist circumference were significantly (P < 0.001) associated with prevalence of prediabetes and T2D. No normal-weight woman (BMI < 25 kg/m(2)) was diagnosed with (TD)-D-2. The prevalence of BMI >= 25 kg/m(2) was 66% (578/876). 91% of women (21/23) with T2D had BMI >= 30 kg/m(2). Testosterone levels and PCOS phenotype did not predict 2-h glucose levels during OGTT after adjustment for BMI and age. LIMITATIONS, REASONS FOR CAUTION: The present study included cross-sectional data and prospective studies are needed to confirm our results. These results may not apply to populations of other ethnic origin. WIDER IMPLICATIONS OF THE FINDINGS: Routine OGTT may not be indicated in normal-weight women with PCOS.
  • Piltonen, Terhi T., et al. (författare)
  • Awareness of polycystic ovary syndrome among obstetrician-gynecologists and endocrinologists in Northern Europe
  • 2019
  • Ingår i: ; 14:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To date, little is known about differences in the knowledge, diagnosis making and treatment strategies of health care providers regarding polycystic ovary syndrome (PCOS) across different disciplines in countries with similar health care systems. To inform guideline translation, we aimed to study physician reported awareness, diagnosis and management of PCOS and to explore differences between medical disciplines in the Nordic countries and Estonia.Methods: This cross-sectional survey was conducted among 382 endocrinologists and obstetrician gynaecologists in the Nordic countries and Estonia in 2015-2016. Of the participating physicians, 43% resided in Finland, 18% in Denmark, 16% in Norway, 13% in Estonia, and 10% in Sweden or Iceland, and 75% were obstetrician-gynaecologists. Multivariable logistic regression models were run to identify health care provider characteristics for awareness, diagnosis and treatment of PCOS.Results: Clinical features, lifestyle management and comorbidity were commonly recognized in women with PCOS, while impairment in psychosocial wellbeing was not well acknowledged. Over two-thirds of the physicians used the Rotterdam diagnostic criteria for PCOS. Medical endocrinologists more often recommended lifestyle management (OR = 3.6, CI 1.6-8.1) or metformin (OR = 5.0, CI 2.5-10.2), but less frequently OCP (OR = 0.5, CI 0.2-0.9) for non fertility concerns than general obstetrician-gynaecologists. The physicians aged <35 years were 2.2 times (95% CI 1.1-4.3) more likely than older physicians to recommend lifestyle management for patients with PCOS for fertility concerns. Physicians aged 46-55 years were less likely to recommend oral contraceptive pills (OCP) for patients with PCOS than physicians aged >56 (adjusted odds ratio (OR) = 0.4, 95% CI 0.2-0.8).Conclusion: Despite well-organized healthcare, awareness, diagnosis and management of PCOS is suboptimal, especially in relation to psychosocial comorbidities, among physicians in the Nordic countries and Estonia. Physicians need more education on PCOS and evidence based information on Rotterdam diagnostic criteria, psychosocial features and treatment of PCOS, with the recently published international PCOS guideline well needed and welcomed.
  • Pinola, Pekka, et al. (författare)
  • Normo- and hyperandrogenic women with polycystic ovary syndrome exhibit an adverse metabolic profile through life
  • 2017
  • Ingår i: Fertility and Sterility. - : ELSEVIER SCIENCE INC. - 0015-0282 .- 1556-5653. ; 107:3, s. 788-
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To compare the metabolic profiles of normo- and hyperandrogenic women with polycystic ovary syndrome (PCOS) with those of control women at different ages during reproductive life. Design: Case-control study. Setting: Not applicable. Patient(s): In all, 1,550 women with normoandrogenic (n = 686) or hyperandrogenic (n = 842) PCOS and 447 control women were divided into three age groups: < 30, 30-39, and > 39 years). Interventions(s): None. Main Outcome Measure(s): Body mass index (BMI), waist circumference, blood pressure, glucose, insulin, cholesterol, lipoproteins, triglycerides and high-sensitivity C-reactive protein. Result(s): Both normo- and hyperandrogenic women with PCOS were more obese, especially abdominally. They had increased serum levels of insulin (fasting and in oral glucose tolerance tests), triglycerides, low-density lipoprotein, and total cholesterol, higher blood pressure, and lower high-density lipoprotein levels independently from BMI compared with the control population as early as from young adulthood until menopause. The prevalence of metabolic syndrome was two-to fivefold higher in women with PCOS compared with control women, depending on age and phenotype, and the highest prevalence was observed in hyperandrogenic women with PCOS at late reproductive age. Conclusion(s): When evaluating metabolic risks in women with PCOS, androgenic status, especially abdominal obesity and age, should be taken into account, which would allow tailored management of the syndrome from early adulthood on.
  • Roller-Wirnsberger, Regina, et al. (författare)
  • European postgraduate curriculum in geriatric medicine developed using an international modified Delphi technique
  • 2019
  • Ingår i: Age and Ageing. - : Oxford University Press. - 1468-2834. ; 48:2, s. 291-299
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: the European Union of Medical Specialists (UEMS-GMS) recommendations for training in Geriatric Medicine were published in 1993. The practice of Geriatric Medicine has developed considerably since then and it has therefore become necessary to update these recommendations.Methods: under the auspices of the UEMS-GMS, the European Geriatric Medicine Society (EuGMS) and the European Academy of Medicine of Ageing (EAMA), a group of experts, representing all member states of the respective bodies developed a new framework for education and training of specialists in Geriatric Medicine using a modified Delphi technique. Thirty-two expert panel members from 30 different countries participated in the process comprising three Delphi rounds for consensus. The process was led by five facilitators.Results: the final recommendations include four different domains: 'General Considerations' on the structure and aim of the syllabus as well as quality indicators for training (6 sub-items), 'Knowledge in patient care' (36 sub-items), 'Additional Skills and Attitude required for a Geriatrician' (9 sub-items) and a domain on 'Assessment of postgraduate education: which items are important for the transnational comparison process' (1 item).Conclusion: the current publication describes the development of the new recommendations endorsed by UEMS-GMS, EuGMS and EAMA as minimum training requirements to become a geriatrician at specialist level in EU member states.
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