Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

A comparison of the changes in cardiac output and systemic vascular resistance during exercise following high-fat meals containing DHA or EPA

Long-chain n-3 PUFA can lower blood pressure (BP) but their acute effects on cardiac output, BP and systemic vascular resistance (SVR) in response to dynamic exercise are uncertain. We compared the effects of high-fat meals rich in EPA (20?:?5n-3), DHA (22?:?6n-3) or oleic acid (control) on cardiac output, BP and SVR in response to exercise stress testing. High-fat meals (50?g fat) containing high-oleic sunflower oil enriched with 4·7?g of either EPA or DHA v. control (high-oleic sunflower oil only) were fed to twenty-two healthy males using a randomised cross-over design. Resting measurements of cardiac output, heart rate and BP were made before and hourly over 5?h following the meal. A standardised 12?min exercise test was then conducted with further measurements made during and post-exercise. Blood samples were collected at fasting, 5?h postprandially and immediately post-exercise for the analysis of lipid, glucose and 8-isoprostane-F2α (8-iso-PGF2α). Plasma concentrations of EPA and DHA increased by 0·22?mmol/l 5?h following the EPA and DHA meals, respectively, compared with the control (P?相似文献   

Hearing-related,health-related quality of life in patients who have undergone otosclerosis surgery: A long-term follow-up study

Objectives: The aims of the study were to assess health-related quality of life and hearing-related disability in subjects with otosclerosis 30 years after surgery. Design: An observational study was performed. Medical records were reviewed, a clinical examination as well as audiometric assessments were performed. Generic health-related quality of life was assessed by the SF-36v2 and hearing disability by a shortened version of SSQ (speech spatial and qualities of hearing scale). Study sample: Sixty-five individuals, who had undergone stapedectomy in 1977-79 at a tertiary referral center. Results: Generic health-related quality of life according to SF-36 subscale scores was comparable to that of an age- and sex-matched reference population. The SF-36 mental component summary score (MCS) was, however, significantly better than that of the reference population. The mental and physical summary component scores correlated significantly to hearing disability measured by the SSQ but not to hearing impairment. Hearing disability was displayed in all SSQ sub-scores, especially in more complex listening situations and in the localization of sounds. Conclusions: This study shows that individuals with otosclerosis, 30 years after surgery, have a good generic health-related quality of life, despite moderate to severe hearing loss and significant hearing disabilities.     

Therapeutic and etiologic considerations related to blood group and triggers in psoriasis—A retrospective study

The aim of this study was to investigate the relationship between the ABO blood, groups and triggers, including food, of psoriasis. A total of 683 psoriasis patients were included in the retrospective study and divided into groups based on their blood group (ABO). Patients were asked to complete a series questions related to the effect of certain foods and other triggers on their psoriasis symptoms. A significant difference between blood groups and the effect of different triggers on the initiation and exacerbation of psoriasis was noted. Furthermore, similarities in response were found between blood groups sharing the same alleles, such as A and AB, or B and AB. Results from this study suggest a link between blood group type and triggering factors of psoriasis. The data show that different blood groups are significantly more likely to have different initiating and exacerbating triggers for psoriasis.     

Psychological aspects of aesthetic and cosmetic surgery: Clinical and therapeutic implications

Recently there is a surge in cosmetic and aesthetic surgery procedures. Several patient seeking various cosmetics procedures present to aesthetic surgery clinics and demanding procedures which are out of proportion. Several of these patients have under‐recognized or untreated psychiatric disorders. Proper screening and evaluation of these patients could save money and resources. This brief review focuses on current trends, clinical and psychological assessment and expectations on the part of patients and recommendations regarding management of these patients.     

Multimodality imaging in diabetic heart disease

Diabetic heart disease is currently defined as left ventricular dysfunction that occurs independently of coronary artery disease and hypertension. Its underlying etiology is likely to be multifactorial, acting synergistically together to cause myocardial dysfunction. Multimodality cardiac imaging, such as echocardiography, nuclear, computed tomography, and magnetic resonance imaging, can provide invaluable insight into different aspects of the disease process, from imaging at the cellular level for altered myocardial metabolism to microvascular and endothelial dysfunction, autonomic neuropathy, coronary atherosclerosis, and finally, interstitial fibrosis with scar formation. Furthermore, cardiac imaging is pivotal in diagnosing diabetic heart disease. Thus, the aim of the present review is to illustrate the role of multimodality cardiac imaging in elucidating the underlying pathophysiologic mechanisms of diabetic heart disease.     

Prolactin (PRL) receptor gene expression in mouse adipose tissue: increases during lactation and in PRL-transgenic mice

There are indications that PRL may exert important metabolic actions on adipose tissue in different species. However, with the exception of birds, the receptor has not been identified in white adipose tissue. The present study was designed to examine the possible expression and regulation of the PRL receptor (PRLR) in mouse adipose tissue. The long PRLR messenger RNA (mRNA) splice form (L-PRLR) and two short splice forms (S2- and S3-PRLR) were detected in mouse adipose tissue by RT-PCR. Furthermore, L-PRLR mRNA was detected by ribonuclease protection assay. Immunoreactive PRLR with a relative molecular mass of 95,000 was revealed by immunoblotting. Furthermore, L-PRLR mRNA expression was demonstrated in primary isolated adipocytes. In mouse adipose tissue, the level of L-PRLR mRNA expression increased 2.3-fold during lactation compared with those in virgin and pregnant mice. In contrast, in the liver the expression of L-PRLR increased 3.4-fold during pregnancy compared with those in virgin and lactating mice. When comparing the levels of L-PRLR expression in virgin female and male mice, no difference was detected in adipose tissue. However, in virgin female liver the expression was 4.5-fold higher than that in male liver. As PRL up-regulates its own receptor in some tissues, we analyzed L-PRLR expression in PRL-transgenic female and male mice. In PRL-transgenic mice L-PRLR expression was significantly increased in both adipose tissue (1.4-fold in females and 2.4-fold in males) and liver (1.9-fold in females and 2.7-fold in males) compared with that in control mice. Furthermore, in female PRL-transgenic mice retroperitoneal adipose tissue was decreased in weight compared with that in control mice. However, no difference was detected when comparing the masses of parametrial adipose tissue. Our results suggest a direct role for PRL, mediated by PRLR, in modulating physiological events in adipose tissue.