Association of PET-based estradiol-challenge test for breast cancer progesterone receptors with response to endocrine therapy

Clinical estrogen receptor (ER) testing for breast cancer is limited in predicting response to endocrine therapy (ET). In this phase 2 clinical trial, authors demonstrate that the responsiveness to ET can be predicted by use of PET/CT with 21-[18F]fluorofuranylnorprogesterone (FFNP) to detect the change in tumor progesterone receptor (PgR) levels after a one-day estradiol challenge

Management of incomplete abortions at South African public hospitals

Objective. The objective of this report was to review and describe the management of incomplete abortion by public sector hospitals.Design. A descriptive study in which data were collected prospectively from routine hospital records on all women admitted with incomplete abortion to a stratified random sample of hospitals between 14 and 28 September 1994.Setting. Public sector hospitals in South Africa.Patients. Women with incomplete abortions.Main outcome measures. Length of hospital stay, details of medical management, details of surgical management, determinants of the above.Main results. Data were collected on 803 patients from the 56 participating hospitals. Of these, 767 (95.9%) were in hospital for 1 day or more, and 753 (95.3%) women underwent evacuation of the uterus. Sharp curettage wasthe method employed in 726 (96.9%) and general anaesthesia was used for 601 (88%) of the women requiring uterine evacuation. Antibiotics were prescribed for 396 (49.5%) and blood transfusions were administered to 125 (17%) women. Statistical analysis showed length of stay to be longer in small hospitals (under 500 beds) and when the medical condition was more severe. Antibiotic  usage and blood transfusion were more common with increasing severity and a low haemoglobin level on admission. However, some inappropriate management was identified with regard to both.Main conclusions. It is suggested that uncomplicated incomplete abortion can be more effectively and safely managed using the manual vacuum aspiration technique with sedation/analgesia as an outpatient procedure. Attention should be directed at the introduction of this management routine at all types of hospital and to the ensuring of appropriate management of women with complicated abortion

Salicylaldoximes and anthranylaldoximes as alternatives to phenol-based estrogen receptor ligands

Estrogens play a crucial role in the development and function of female reproductive tissues. They have positive effects on the maintenance of bone mineral density, on the liver, and on the cardiovascular and central nervous systems. Selective Estrogen Receptor Modulators (SERMs) are particularly attractive as therapeutic agents because they are able to block estrogen action at those sites where stimulation would be undesirable, such as the breast and uterus, but at the same time stimulate estrogen actions in other tissues where they are desired, such as the bone and liver. Most synthetic estrogen receptor ligands possess a phenolic ring, mimicking the phenolic "Aring" of the natural ligand estradiol. In an attempt to increase the structural diversity of estrogen receptor (ER) ligands, we designed and synthesized molecules containing unprecedented replacements of the prototypical phenolic "A-ring" of estrogens with an oxime and a hydroxy- (salicylaldoximes) or aminomoieties (anthranylaldoximes), forming intramolecularly H-bonded pseudocycles. These new classes of compounds showed interesting ER binding properties on both receptor subtypes (ERα and ERβ). These results proved that the six-membered ring formed by an intramolecular hydrogen bond, and containing an exocyclic oxime OH, is an effective stereoelectronic replacement of the phenolic ring of typical ER ligands

A case control study of breast cancer risk and exposure to injectable progestogen contraceptives

No Abstract

Mortality after admission for acute myocardial infarction in Aboriginal and non-Aboriginal people in New South Wales, Australia: a multilevel data linkage study

Background - Heart disease is a leading cause of the gap in burden of disease between Aboriginal and non-Aboriginal Australians. Our study investigated short- and long-term mortality after admission for Aboriginal and non-Aboriginal people admitted with acute myocardial infarction (AMI) to public hospitals in New South Wales, Australia, and examined the impact of the hospital of admission on outcomes. Methods - Admission records were linked to mortality records for 60047 patients aged 25–84 years admitted with a diagnosis of AMI between July 2001 and December 2008. Multilevel logistic regression was used to estimate adjusted odds ratios (AOR) for 30- and 365-day all-cause mortality. Results - Aboriginal patients admitted with an AMI were younger than non-Aboriginal patients, and more likely to be admitted to lower volume, remote hospitals without on-site angiography. Adjusting for age, sex, year and hospital, Aboriginal patients had a similar 30-day mortality risk to non-Aboriginal patients (AOR: 1.07; 95% CI 0.83-1.37) but a higher risk of dying within 365 days (AOR: 1.34; 95% CI 1.10-1.63). The latter difference did not persist after adjustment for comorbid conditions (AOR: 1.12; 95% CI 0.91-1.38). Patients admitted to more remote hospitals, those with lower patient volume and those without on-site angiography had increased risk of short and long-term mortality regardless of Aboriginal status. Conclusions - Improving access to larger hospitals and those with specialist cardiac facilities could improve outcomes following AMI for all patients. However, major efforts to boost primary and secondary prevention of AMI are required to reduce the mortality gap between Aboriginal and non-Aboriginal people

Delineation of a unique protein-protein interaction site on the surface of the estrogen receptor

Recent studies have identified a series of estrogen receptor (ER)interacting peptides that recognize sites that are distinct from the classic coregulator recruitment (AF2) region. Here, we report the structural and functional characterization of an ER alpha-specific peptide that binds to the liganded receptor in an AF2-independent manner. The 2-angstrom crystal structure of the ER/peptide complex reveals a binding site that is centered on a shallow depression on the beta-hairpin face of the ligand-binding domain. The peptide binds in an unusual extended conformation and makes multiple contacts with the ligand-binding domain. The location and architecture of the binding site provides an insight into the peptide's ER subtype specificity and ligand interaction preferences. In vivo, an engineered coactivator containing the peptide motif is able to strongly enhance the transcriptional activity of liganded ER alpha, particularly in the presence of 4-hydroxytamoxifen. Furthermore, disruption of this binding surface alters ER's response to the coregulator TIF2. Together, these results indicate that this previously unknown interaction site represents a bona fide control surface involved in regulating receptor activity

Challenges in managing acute cardiovascular diseases and follow up care in rural areas: a narrative review

This narrative review explores relevant literature that is related to the challenges in implementing evidence-based management for clinicians in rural and remote areas, while primarily focussing on management of acute coronary syndrome (ACS) and follow up care. A targeted literature search around rural/urban differences in the management of ACS, cardiovascular disease, and cardiac rehabilitation identified multiple issues that are related to access, including the ability to pay, transport and geographic distances, delays in patients seeking care, access to diagnostic testing, and timely treatment in an appropriate facility. Workforce shortages or lack of ready access to relevant expertise, cultural differences, and complexity that arises from comorbidities and from geographical isolation amplified diagnostic challenges. Given the urgency in management of ACS, rural clinicians must act quickly to achieve optimal patient outcomes. New technologies and quality improvement approaches enable better access to rapid diagnosis, as well as specialist input and care. Achieving an uptake of cardiac rehabilitation in rural and remote settings poses challenges that may reduce with the use of alternative models to centre-based rehabilitation and use of modern technologies. Expediting improvement in cardiovascular outcomes and reducing rural disparities requires system changes and that clinicians embrace attention to prevention, emergency management, and follow up care in rural contexts.Sandra C. Thompson, Lee Nedko, Judith Katzenellenbogen, Mohammad Akhtar Hussain and Frank Sanfilipp

Standardization of epidemiological surveillance of acute rheumatic fever

Acute rheumatic fever (ARF) is a multiorgan inflammatory disorder that results from the body’s autoimmune response to pharyngitis or a skin infection caused by Streptococcus pyogenes (Strep A). Acute rheumatic fever mainly affects those in low- and middle-income nations, as well as in indigenous populations in wealthy nations, where initial Strep A infections may go undetected. A single episode of ARF puts a person at increased risk of developing long-term cardiac damage known as rheumatic heart disease. We present case definitions for both definite and possible ARF, including initial and recurrent episodes, according to the 2015 Jones Criteria, and we discuss current tests available to aid in the diagnosis. We outline the considerations specific to ARF surveillance methodology, including discussion on where and how to conduct active or passive surveillance (eg, early childhood centers/schools, households, primary healthcare, administrative database review), participant eligibility, and the surveillance population. Additional considerations for ARF surveillance, including implications for secondary prophylaxis and follow-up, ARF registers, community engagement, and the impact of surveillance, are addressed. Finally, the core elements of case report forms for ARF, monitoring and audit requirements, quality control and assurance, and the ethics of conducting surveillance are discussed

Regulatory function of the P295-T311 motif of the estrogen receptor α - does proteasomal degradation of the receptor induce emergence of peptides implicated in estrogenic responses?

The way in which estrogen receptor α (ERα) mediates gene transcription and hormone-dependent cancer cell proliferation is now being largely reconsidered in view of several recent discoveries. ERα-mediated transcription appears to be a cyclic and transient process where the proteasome - and thus receptor degradation - plays a pivotal role. In view of our recent investigations, which demonstrate the estrogenic activity of a synthetic peptide corresponding to a regulatory motif of the receptor (ERα17p), we propose that ERα proteasomal degradation could induce the emergence of regulatory peptide(s). The latter would function as a signal and contribute to the ERα activation process, amplifying the initial hormonal stimulation and giving rise to sustained estrogenic response