The endocrine influence on the bone microenvironment in early breast cancer

Multiple factors influence the survival of disseminated breast tumour cells (DTCs) in bone. Whilst gene signature studies have identified genes that predict a propensity of tumours to metastasise to bone, the bone environment is key in determining the fate of these tumour cells. Breast cancer cells locate to specific niches within the bone that support their survival, regulated by host factors within the bone microenvironment including bone cells, cells of the bone micro vasculature, immune cells and the extracellular matrix. Reproductive endocrine hormones affect bone and clinical studies across the menopausal transition have provided comprehensive understanding of the changes in the bone microenvironment during this time. Menopause is characterised by a decrease in ovarian oestradiol and inhibins, with an increase in pituitary follicle stimulating hormone and this review will focus on the role of these 3 hormones in determining the fate of DTCs in bone. Both in vivo and clinical data suggest premenopausal bone is a conducive environment for growth of breast cancer cells in bone. Adjuvant cancer treatment aims to reduce the risk of tumour recurrence by targeting DTCs and drugs targeting the bone resorbing osteoclasts, such as bisphosphonates, have been evaluated in this setting. Both preclinical and adjuvant clinical studies and have shown that bisphosphonates ability to decrease tumour growth in bone is influenced by levels of endocrine hormones, with enhanced effects in a postmenopausal bone microenvironment. The challenge is to understand the molecular mechanisms behind this phenomenon and to evaluate if alternative adjuvant bone targeted therapies may be effective in premenopausal women

Concomitant Intraoperative Radiofrequency and Microwave Ablation of Atrial Fibrillation and Repair of Atrial Septal Defect

Atrial fibrillation (AF) is the most frequent form of atrial arrhythmias in adults with congenital heart disease. Some serious complications are related with the presence of AF after surgery. Because of the complexity and the risk of bleeding, the Maze III procedure has been largely replaced by alternative energy sources. A patient with multiple atrial septal defects (ASD) and AF underwent surgical closure with autologous pericardial patch and radiofrequency and microwave ablation of AF

Concomitant Radiofrequency ??? Microwave Ablation and Atrial Septal Defect Repair

Atrial fibrillation (AF) is the most frequent form of atrial arrhythmias in adults with congenital heart disease. Some serious complications are related with the presence of AF after surgery. Because of the complexity and the risk of bleeding, the Maze III procedure has been largely replaced by alternative energy sources. A patient with multiple atrial septal defects (ASD) and AF underwent surgical closure with autologous pericardial patch and bipolar radiofrequency and microwave ablation

Ontogenetic Profile of the Expression of Thyroid Hormone Receptors in Rat and Human Corpora Cavernosa of the Penis

Introduction. In the last few years, various studies have underlined a correlation between thyroid function and male sexual function, hypothesizing a direct action of thyroid hormones on the penis. Aim. To study the spatiotemporal distribution of mRNA for the thyroid hormone nuclear receptors (TR) alpha 1, alpha 2 and beta in the penis and smooth muscle cells (SMCs) of the corpora cavernosa of rats and humans during development. Methods. We used several molecular biology techniques to study the TR expression in whole tissues or primary cultures from human and rodent penile tissues of different ages. Main Outcome Measure. We measured our data by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) amplification, Northern blot and immunohistochemistry. Results. We found that TR alpha 1 and TR alpha 2 are both expressed in the penis and in SMCs during ontogenesis without development-dependent changes. However, in the rodent model, TR beta shows an increase from 3 to 6 days post natum (dpn) to 20 dpn, remaining high in adulthood. The same expression profile was observed in humans. While the expression of TR beta is strictly regulated by development, TR alpha 1 is the principal isoform present in corpora cavernosa, suggesting its importance in SMC function. These results have been confirmed by immunohistochemistry localization in SMCs and endothelial cells of the corpora cavernosa. Conclusions. The presence of TRs in the penis provides the biological basis for the direct action of thyroid hormones on this organ. Given this evidence, physicians would be advised to investigate sexual function in men with thyroid disorders. Carosa E, Di Sante S, Rossi S, Castri A, D'Adamo F, Gravina GL, Ronchi P, Kostrouch Z, Dolci S, Lenzi A, and Jannini EA. Ontogenetic profile of the expression of thyroid hormone receptors in rat and human corpora cavernosa of the penis. J Sex Med 2010;7:1381-1390

Impact of month of birth on the development of autoimmune thyroid disease in the United Kingdom and Europe

CONTEXT: Viral/bacterial infection is proposed as a trigger for the autoimmune thyroid diseases (AITD): Graves' disease (GD) and Hashimoto's thyroiditis (HT). Previous studies in European Caucasian AITD subjects found higher birth rates in the autumn/winter, suggesting those born in the autumn/winter experience increased viral/bacterial exposure after birth, impacting upon immune system development and predisposing to AITD later in life. OBJECTIVE: Month of birth effects were investigated in three independent European Caucasian AITD datasets. DESIGN: Variation in GD and HT onset was compared across months and seasons, with fluctuations across all 12 months analyzed using a Walter-Elwood test. SETTING: The study was conducted at a research laboratory. PATIENTS: National UK Caucasian AITD Case Control Collection (2746 GD and 502 HT compared with 1 423 716 UK births), National UK Caucasian GD Family Collection (239 GD and 227 unaffected siblings), and OXAGEN AITD Caucasian Family Collection (885 GD, 717 HT, and 794 unaffected siblings of European Caucasian decent). MAIN OUTCOME MEASURES: Case-control and family-based association studies were measured. RESULTS: No consistent month of birth effects were detected in GD females or males across all three collections. In HT females from the OXAGEN AITD Caucasian Family Collection, slightly higher birth rates were detected in autumn (Walter's test statistic = 7.47, P = .024) however, this was not seen in the HT females from the case-control cohort. CONCLUSION: Our results suggest in UK/Northern European Caucasian GD subjects, month of birth does not impact on AITD development. Although some month of birth effects for HT females in one collection cannot be excluded, only further work in larger European Caucasian AITD collections can confirm these effects

Targeted biological therapies for Graves’ disease and thyroid-associated ophthalmopathy. Focus on B-cell depletion with Rituximab

Based on experience from the treatment of other autoimmune diseases and because of the limitations imposed by existing therapeutic options for Graves’ disease (GD) and thyroid-associated ophthalmopathy (TAO), rituximab (RTX) was recently proposed as a novel therapy option. Here, we summarize the rationale for using RTX; give an overview of the possible mechanisms of action; and give an account of its effects and side-effects when used in GD and TAO. Scant evidence, originating from only a few methodologically inhomogeneous studies, suggests that RTX may prolong remission for hyperthyroidism over that seen with antithyroid drugs, at least in mild GD. Furthermore, in patients with TAO, who are unresponsive to conventional immunosuppressive therapy, RTX seems efficacious. As we wait for larger-scale randomized studies, RTX, should be considered experimental and reserved for patients who do not respond favourably to conventional therapy. It is the first in what is likely to be a series of new and emerging treatments specifically targeting relevant components of the immune system. Further studies will hopefully lead to improved and better tailored, individualized therapy for GD and especially TAO.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79171/1/j.1365-2265.2010.03806.x.pd

Overweight and obesity in relation to cardiovascular disease risk factors among medical students in Crete, Greece

BACKGROUND: Recent data indicate increasing rates of adult obesity and mortality from cardiovascular disease (CVD) in Greece. No data, however, are available on prevalence of overweight and obesity in relation to CVD risk factors among young adults in Greece. METHODS: A total of 989 third-year medical students (527 men, 462 women), aged 22 ± 2 years, were recruited from the University of Crete during the period 1989–2001. Anthropometric measures and blood chemistries were obtained. The relationships between obesity indices (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHpR], waist-to-height ratio [WHtR]) and CVD risk factor variables (blood pressure, glucose, serum lipoproteins) were investigated. RESULTS: Approximately 40% of men and 23% of women had BMI ≥ 25.0 kg/m(2). Central obesity was found in 33.4% (average percentage corresponding to WC ≥ 90 cm, WHpR ≥ 0.9 and WHtR ≥ 50.0) of male and 21.7% (using WC ≥ 80 cm, WHpR ≥ 0.8, WHtR ≥ 50.0) of female students. Subjects above the obesity indices cut-offs had significantly higher values of CVD risk factor variables. BMI was the strongest predictor of hypertension. WHtR in men and WC in women were the most important indicators of dyslipidaemia. CONCLUSION: A substantial proportion of Greek medical students were overweight or obese, obesity status being related to the presence of hypertension and dyslipidaemia. Simple anthropometric indices can be used to identify these CVD risk factors. Our results underscore the need to implement health promotion programmes and perform large-scale epidemiological studies within the general Greek young adult population