827 research outputs found

    New Zealand regions, 1986 – 2001: Hospitalisation and some related health facts

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    Once age and gender composition is controlled for, regional health differentials are a function of problems of health service delivery, of socio-economic variance, and overall Māori Pakeha health differences. They indicate relative levels of exclusion and of inequality. This paper shows that these differentials follow in general the patterns seen in other papers in this series

    MMTV-PyMT and derived Met-1 mouse mammary tumor cells as models for studying the role of the androgen receptor in triple-negative breast cancer progression

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    Triple-negative breast cancer (TNBC) has a faster rate of metastasis compared to other breast cancer subtypes and no effective targeted therapies are currently FDA-approved. Recent data indicate that the androgen receptor (AR) promotes tumor survival and may serve as a potential therapeutic target in TNBC. Studies of AR in disease progression and the systemic effects of anti-androgens have been hindered by the lack of an AR-positive (AR+) immunocompetent preclinical model. In this study we identified the transgenic MMTV-PyMT (mouse mammary tumor virus-polyoma middle tumor antigen) mouse mammary gland carcinoma model of breast cancer and Met-1 cells derived from this model as tools to study the role of AR in breast cancer progression. AR protein expression was examined in late-stage primary tumors and lung metastases from MMTV-PyMT mice as well as in Met-1 cells by immunohistochemistry (IHC). Sensitivity of Met-1 cells to the AR agonist dihydrotestosterone (DHT) and anti-androgen therapy was examined using cell viability, migration/invasion, and anchorage-independent growth assays. Late-stage primary tumors and lung metastases from MMTV-PyMT mice and Met-1 cells expressed abundant nuclear AR protein, while negative for estrogen and progesterone receptors. Met-1 sensitivity to DHT and AR antagonists demonstrated a reliance on AR for survival, and AR antagonists inhibited invasion and anchorage-independent growth. These data suggest that the MMTV-PyMT model and Met-1 cells may serve as valuable tools for mechanistic studies of the role of AR in disease progression and how anti-androgens affect the tumor microenvironment

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

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    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 ERÎČ). 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

    Management of incomplete abortions at South African public hospitals

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    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

    Exploring disparities in acute myocardial infarction events between Aboriginal and non-Aboriginal Australians: roles of age, gender, geography and area-level disadvantage

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    We investigated disparities in rates of acute myocardial infarction (AMI) between Aboriginal and non-Aboriginal people in the 199 Statistical Local Areas (SLAs) in New South Wales, Australia. Using routinely collected and linked hospital and mortality data from 2002 to 2007, we developed multilevel Poisson regression models to estimate the relative rates of first AMI events in the study period accounting for area of residence. Rates of AMI in Aboriginal people were more than two times that in non-Aboriginal people, with the disparity greatest in more disadvantaged and remote areas. AMI rates in Aboriginal people varied significantly by SLA, as did the Aboriginal to non-Aboriginal rate ratio. We identified almost 30 priority areas for universal and targeted preventive interventions that had both high rates of AMI for Aboriginal people and large disparities in rates

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

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    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

    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?

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    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
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