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Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial

Background Olaparib, a novel, orally active poly(ADP-ribose) polymerase (PARP) inhibitor, induced synthetic lethality in BRCA-deficient cells. A maximum tolerated dose and initial signal of efficacy in BRCA-deficient ovarian cancers have been reported. We therefore assessed the efficacy, safety, and tolerability of olaparib alone in women with BRCA1 or BRCA2 mutations and advanced breast cancer. M

Adipose tissue is inflamed in NAFLD due to obesity but not in NAFLD due to genetic variation in PNPLA3

The rs738409 C > G single-nucleotide polymorphism in PNPLA3 leads to a missense mutation (I148M) which increases liver fat but does not cause insulin resistance. We hypothesised that patients with non-alcoholic fatty liver disease (NAFLD) due to the PNPLA3 variant ('PNPLA3 NAFLD'aEuro parts per thousand= PNPLA3-148MM) do not have adipose tissue (AT) inflammation in contrast with those with NAFLD d

Comorbidities and Mortality in Bipolar Disorder A Swedish National Cohort Study

IMPORTANCE Bipolar disorder is associated with premature mortality, but the specific causes and underlying pathways are unclear. OBJECTIVE To examine the physical health effects of bipolar disorder using outpatient and inpatient data for a national population. DESIGN, SETTING, AND PARTICIPANTS National cohort study of 6 587 036 Swedish adults, including 6618 with bipolar disorder. MAIN OUTCOMES AN

Depressive symptoms, atherosclerotic burden and cerebral blood flow disturbances in a cohort of octogenarian men from a general population

Background: The aim of this study was to examine in elderly men a relationship between depressive symptoms, peripheral vascular disease and cerebral blood flow (CBF). Methods: Population-based cohort study started with an examination of 809 men at age 55, followed by the first (age 68ys) and second follow up (age 82ys). 128 survivors were examined at age 82 with Tc-99m-HMPAO-SPECT to estimate CBF,

Intermittent PTH((1-34)) does not increase union rates in open rat femoral fractures and exhibits attenuated anabolic effects compared to closed fractures.

Intermittent Parathyroid Hormone (PTH)((1-34)) has an established place in osteoporosis treatment, but also shows promising results in models of bone repair. Previous studies have been dominated by closed fracture models, where union is certain. One of the major clinical needs for anabolic therapies is the treatment of open and high energy fractures at risk of non-union. In the present study we th

Severe Hemodilution - Clinical and Experimental Studies

Popular Abstract in Swedish Under det senaste decenniet har risker med och alternativ till allogent blod (blod från främmande givare) debatterats mycket pga. risken för smitta, allergiska reaktioner, samt starka indicier som talar för att blod från främmande givare kan påverka immunförsvaret hos mottagaren. Därför vill man gärna begränsa mängden tillfört givarblod under kirurgiska ingrepp på barn,In children, it is often desirable to minimize allogenic blood transfusion, and this thesis explores the physiology of an alternative method of managing perioperative blood loss: hemodilution with Ringer´s dextran. Methods Clinical studies: Arterial pressure, superior caval venous oxygen saturation (ScvO2) and blood lactate concentration (L) were studied during bone marrow harvesting (BMH) on 23

Mutation Analysis and Hypercholesterolemia: Studies in FH patients and in healthy middle-aged men with high, low, or increasing cholesterol levels during a six-year follow-up (the CRISS study).

Our aims were to characterize familial hypercholesterolemia (FH) in a Swedish FH population and to further elucidate the clinical expression and treatment response in relation to genotype. Secondly, we wanted to identify gene variants, which may have impact on cholesterol levels in apparently healthy subjects. In the search for sequence alterations in the large LDL receptor gene we introduced and

Development of and Recovery from Secondary Hypogonadism in Aging Men: Prospective Results from the EMAS

Context: Secondary hypogonadism is common in aging men; its natural history and predisposing factors are unclear. Objectives: The objectives were 1) to identify factors that predispose eugonadal men (T >= 10.5 nmol/L) to develop biochemical secondary hypogonadism (T < 10.5 nmol/L; LH <= 9.4 U/L) and secondary hypogonadal men to recover to eugonadism; and 2) to characterize clinical features associ

Prospective Longitudinal Study of Thromboelastography and Standard Hemostatic Laboratory Tests in Healthy Women During Normal Pregnancy

BACKGROUND: Hemostatic disorders are common in obstetric complications. Thromboelastography (TEG (R)) simultaneously measures coagulation and fibrinolysis within 10 to 20 minutes. Our primary aim in this prospective longitudinal study was to obtain knowledge about physiological changes in TEG (R) variables during normal pregnancy and 8 weeks postpartum. The secondary aims were to compare TEG (R) v

Validation of podocalyxin-like protein as a biomarker of poor prognosis in colorectal cancer

Background: Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and adverse outcome in several cancer types. We recently demonstrated that overexpression of PODXL is an independent factor of poor prognosis in colorectal cancer (CRC). The aim of this study was to validate these results in two additional indepen

Past, present and future state of the biogeochemical Si cycle in the Baltic Sea

The Baltic Sea is one of many aquatic ecosystems that show long-term declines in dissolved silicate (DSi) concentrations due to anthropogenic alteration of the biogeochemical Si cycle. Reductions in DSi in aquatic ecosystems have been coupled to hydrological regulation reducing inputs, but also with eutrophication, although the relative significance of both processes remains unknown for the observ

Recent Developments of Chlamydia trachomatis and Mycoplasma Infections in Women

The aim of this thesis was to elucidate developments in epidemiology, clinical manifestations and complications in Chlamydia trachomatis (C.trachomatis) and Mycoplasma genitalium (M.genitalium) infection. In study I the frequencies of non-gonococcal salpingitis, gonococcal salpingitis and ectopic pregnancy (EP) were observed over a period of 28 years and correlated to the prevalence of Neisseria g

Obstetric Outcomes in Women With Turner Karyotype EDITORIAL COMMENT

There is concern over the high risk of cardiovascular complications, hypertensive disorders, and other adverse obstetric outcomes among pregnant women with Turner syndrome (TS). A diagnosis of TS is made in some women late in life or not at all. Spontaneous pregnancies are rare in women with TS and are associated with a high rate of complications, especially miscarriage. The use of assisted reprod

Clinical Impact of Second-Generation Everolimus-Eluting Stent Compared With First-Generation Drug-Eluting Stents in Diabetes Mellitus Patients Insights From a Nationwide Coronary Intervention Register

Objectives This study sought to study the second-generation everolimus-eluting stent (EES) as compared with first-generation sirolimus-eluting (SES) and paclitaxel-eluting stents (PES) in diabetes mellitus (DM) patients. Background There are limited data available comparing clinical outcomes in this setting with EES and SES, whereas studies comparing EES with PES are not powered for low-frequency

Linear Metal Chains in Ca2M2X (M = Pd, Pt; X = Al, Ge): Origin of the Pairwise Distortion and Its Role in the Structure Stability

A series of four new analogue phases Ca2M2X (M = Pd, Pt and X = Al, Ge) were prepared by direct combination of the respective elements in stoichiometric mixtures at high temperature in order to analyze the impact of valence electron count (vec) and electronegativity differences (Delta chi) on the structure selection and stability. Their crystal structures, as determined from single-crystal X-ray d

Smoking Predicts Incident Fractures in Elderly Men: Mr OS Sweden

The aim of this study was to investigate the association between smoking and bone mineral density (BMD) and radiographically verified prevalent vertebral fractures and incident fractures in elderly men. At baseline 3003 men aged 69 to 80 years of age from the Swedish Mr Os Study completed a standard questionnaire concerning smoking habits and had BMD of the hip and spine measured using dual-energy

Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial

Background No effective standard treatment exists for patients with radioiodine-refractory, advanced differentiated thyroid carcinoma. We aimed to assess efficacy and safety of vandetanib, a tyrosine kinase inhibitor of RET, VEGFR and EGFR signalling, in this setting. Methods In this randomised, double-blind, phase 2 trial, we enrolled adults (aged >= 18 years) with locally advanced or metastatic

Genetic factors related to racial variation in plasma levels of insulin-like growth factor-1: implications for premenopausal breast cancer risk

The oral contraceptive pill is associated with a modest increase in the risk of early-onset breast cancer in the general population, but it is possible that the risk is higher in certain subgroups of women. The relative risk of breast cancer associated with oral contraceptive use has been reported to be higher for African-American women than for white women. African-American women also have a high

Soft Tissue Sarcoma Patterns multiplicity, heterogeneity and growth characteristics

Soft tissue sarcomas (STS) represent a group of rare and heterogenous tumors that optimally should be diagnosed and treated within multidisciplinary teams. This thesis has studied various aspects ? pathological, genetical, and clinical ? of STS. In study I, we demonstrated that 20% of the patients in a population-based series of 818 STS developed second primary malignancies. An increased risk of

Lower Urinary Tract Symptoms in Stroke Patients

The overall aims of this thesis were to investigate the prevalence, severity and bother of Lower Urinary Tract Symptoms (LUTS) in a clinical sample of stroke patients and to evaluate the effect of pelvic floor muscle training (PFMT) in women with urinary incontinence after ischemic stroke. The thesis consisted of 6 articles based on 4 studies and a review. In the first study (Paper I), the Danish