Birth length and weight as predictors of breast cancer prognosis

Background Birth size, and particularly birth length, is positively associated with breast cancer risk in adulthood. The objective of this study was to examine whether birth size is associated with survival among breast cancer patients. Methods Information on birth size (weight, length and ponderal index (kg/length (m3)) was collected from birth archives for 331 breast cancer patients who were diagnosed at two university hospitals in Norway (Bergen and Trondheim). The patients were followed from the time of diagnosis until death from breast cancer, death from another cause, or to the end of follow-up, and birth size was related to survival, using Cox regression analysis. Results Breast cancer patients with birth length ≥ 52 cm had nearly twice the risk of dying (hazard ratio, 1.92, 95% confidence interval, 1.09-3.41) from breast cancer compared to women with birth length less than 48 cm, after adjustment for place of birth and year of diagnosis. Similar analyses related to birth weight and ponderal index showed no clear association with breast cancer survival. Conclusions Poorer outcome of breast cancer patients with high birth length may reflect effects of factors that stimulate longitudinal growth and simultaneously increase the risk of metastases and fatal outcome. It is possible that the insulin-like growth factor (IGF) system is involved in the underlying mechanisms

Gene conversion in human rearranged immunoglobulin genes

Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V<sub>H</sub> segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V<sub>H</sub> replacements with no addition of untemplated nucleotides at the V<sub>H</sub>–V<sub>H</sub> joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V<sub>H</sub> replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion

Sex steroids, growth factors and mammographic density: a cross-sectional study of UK postmenopausal Caucasian and Afro-Caribbean women

INTRODUCTION: Sex steroids, insulin-like growth factors (IGFs) and prolactin are breast cancer risk factors but whether their effects are mediated through mammographic density, one of the strongest risk factors for breast cancer, is unknown. If such a hormonal basis of mammographic density exists, hormones may underlie ethnic differences in both mammographic density and breast cancer incidence rates. METHODS: In a cross-sectional study of 270 postmenopausal Caucasian and Afro-Caribbean women attending a population-based breast screening service in London, UK, we investigated whether plasma biomarkers (oestradiol, oestrone, sex hormone binding globulin (SHBG), testosterone, prolactin, leptin, IGF-I, IGF-II and IGF binding protein 3 (IGFBP3)) were related to and explained ethnic differences in mammographic percent density, dense area and nondense area, measured in Cumulus using the threshold method. RESULTS: Mean levels of oestrogens, leptin and IGF-I:IGFBP3 were higher whereas SHBG and IGF-II:IGFBP3 were lower in Afro-Caribbean women compared with Caucasian women after adjustment for higher mean body mass index (BMI) in the former group (by 3.2 kg/m(2) (95% confidence interval (CI): 1.8, 4.5)). Age-adjusted percent density was lower in Afro-Caribbean compared with Caucasian women by 5.4% (absolute difference), but was attenuated to 2.5% (95% CI: -0.2, 5.1) upon BMI adjustment. Despite ethnic differences in biomarkers and in percent density, strong ethnic-age-adjusted inverse associations of oestradiol, leptin and testosterone with percent density were completely attenuated upon adjustment for BMI. There were no associations of IGF-I, IGF-II or IGFBP3 with percent density or dense area. We found weak evidence that a twofold increase in prolactin and oestrone levels were associated, respectively, with an increase (by 1.7% (95% CI: -0.3, 3.7)) and a decrease (by 2.0% (95% CI: 0, 4.1)) in density after adjustment for BMI. CONCLUSIONS: These findings suggest that sex hormone and IGF levels are not associated with BMI-adjusted percent mammographic density in cross-sectional analyses of postmenopausal women and thus do not explain ethnic differences in density. Mammographic density may still, however, be influenced by much higher premenopausal hormone levels

Birth weight and breast cancer risk

Exploring whether the positive association between birth weight and breast cancer risk differs by other breast cancer risk factors may help inform speculation about biological mechanism. In these data, high birth weight was associated with breast cancer risk in younger and in more educated women, but was not associated overall

The spatial distribution of radiodense breast tissue: a longitudinal study

Introduction Mammographic breast density is one of the strongest known markers of susceptibility to breast cancer. To date research into density has relied on a single measure ( for example, percent density (PD)) summarising the average level of density for the whole breast, with no consideration of how the radiodense tissue may be distributed. This study aims to investigate the spatial distribution of density within the breast using 493 mammographic images from a sample of 165 premenopausal women (similar to 3 medio-lateral oblique views per woman).Methods Each breast image was divided into 48 regions and the PD for the whole breast ( overall PD) and for each one of its regions ( regional PD) was estimated. The spatial autocorrelation ( Moran's I value) of regional PD for each image was calculated to investigate spatial clustering of density, whether the degree of clustering varied between a woman's two breasts and whether it was affected by age and other known density correlates.Results The median Moran's / value for 165 women was 0.31 (interquartile range: 0.26, 0.37), indicating a clustered pattern. High-density areas tended to cluster in the central regions of the breast, regardless of the level of overall PD, but with considerable between-woman variability in regional PD. The degree of clustering was similar between a woman's two breasts (mean within-woman difference in Moran's / values between left and right breasts = 0.00 (95% confidence interval (CI) = -0.01, 0.01); P = 0.76) and did not change with aging (mean within-woman difference in I values between screens taken on average 8 years apart = 0.01 (95% CI = -0.01, 0.02); P = 0.30). Neither parity nor age at first birth affected the level of spatial autocorrelation of density, but increasing body mass index (BMI) was associated with a decrease in the degree of spatial clustering.Conclusions This study is the first to demonstrate that the distribution of radiodense tissue within the breast is spatially autocorrelated, generally with the high-density areas clustering in the central regions of the breast. The degree of clustering was similar within a woman's two breasts and between women, and was little affected by age or reproductive factors although it declined with increasing BMI

How acceptable are antiretrovirals for the prevention of sexually transmitted HIV? A review of research on the acceptability of oral pre-exposure prophylaxis and treatment as prevention

Recent research has demonstrated how antiretrovirals (ARVs) could be effective in the prevention of sexually transmitted HIV. We review research on the acceptability of oral pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) for HIV prevention amongst potential users. We consider with whom, where and in what context this research has been conducted, how acceptability has been approached, and what research gaps remain. Findings from 33 studies show a lack of TasP research, PrEP studies which have focused largely on men who have sex with men (MSM) in a US context, and varied measures of acceptability. In order to identify when, where and for whom PrEP and TasP would be most appropriate and effective, research is needed in five areas: acceptability of TasP to people living with HIV; motivation for PrEP use and adherence; current perceptions and management of risk; the impact of broader social and structural factors; and consistent definition and operationalisation of acceptability which moves beyond adherence

Birth weight is associated with postmenopausal breast cancer risk in Swedish women

There is some evidence that birth weight is associated with breast cancer. Whether this association differs between premenopausal and postmenopausal ages is still unclear. The results from this study suggest that higher birth weight is a risk factor for postmenopausal breast cancer (OR 1.06, CI 1.00-1.12, per 100 g), independent of selected early-life and adult factors

A Guide for applying a revised version of the PARIHS framework for implementation

<p>Abstract</p> <p>Background</p> <p>Based on a critical synthesis of literature on use of the Promoting Action on Research Implementation in Health Services (PARIHS) framework, revisions and a companion <it>Guide </it>were developed by a group of researchers independent of the original PARIHS team. The purpose of the <it>Guide </it>is to enhance and optimize efforts of researchers using PARIHS in implementation trials and evaluations.</p> <p>Methods</p> <p>Authors used a planned, structured process to organize and synthesize critiques, discussions, and potential recommendations for refinements of the PARIHS framework arising from a systematic review. Using a templated form, each author independently recorded key components for each reviewed paper; that is, study definitions, perceived strengths/limitations of PARIHS, other observations regarding key issues and recommendations regarding needed refinements. After reaching consensus on these key components, the authors summarized the information and developed the <it>Guide</it>.</p> <p>Results</p> <p>A number of revisions, perceived as consistent with the PARIHS framework's general nature and intent, are proposed. The related <it>Guide </it>is composed of a set of reference tools, provided in Additional files. Its core content is built upon the basic elements of PARIHS and current implementation science.</p> <p>Conclusions</p> <p>We invite researchers using PARIHS for targeted evidence-based practice (EBP) implementations with a strong task-orientation to use this <it>Guide </it>as a companion and to apply the revised framework prospectively and comprehensively. Researchers also are encouraged to evaluate its use relative to perceived strengths and issues. Such evaluations and critical reflections regarding PARIHS and our <it>Guide </it>could thereby promote the framework's continued evolution.</p

Nondense mammographic area and risk of breast cancer

Introduction The mechanisms underlying the strong association between percentage dense area on a mammogram and the risk of breast cancer are unknown. We investigated separately the absolute dense area and the absolute nondense area on mammograms in relation to breast cancer risk. Methods We conducted a nested case-control study on prediagnostic mammographic density measurements and risk of breast cancer in the Nurses\u27 Health Study and the Nurses\u27 Health Study II. Premenopausal mammograms were available from 464 cases and 998 controls, and postmenopausal mammograms were available from 960 cases and 1,662 controls. We used a computer-assisted thresholding technique to measure mammographic density, and we used unconditional logistic regression to calculate OR and 95% CI data. Results Higher absolute dense area was associated with a greater risk of breast cancer among premenopausal women (ORtertile 3 vs 1 = 2.01, 95% CI = 1.45 to 2.77) and among postmenopausal women (ORquintile 5 vs 1 = 2.19, 95% CI = 1.65 to 2.89). However, increasing absolute nondense area was associated with a decreased risk of breast cancer among premenopausal women (ORtertile 3 vs 1 = 0.51, 95% CI = 0.36 to 0.72) and among postmenopausal women (ORquintile 5 vs 1 = 0.46, 95% CI = 0.34 to 0.62). These associations changed minimally when we included both absolute dense area and absolute nondense area in the same statistical model. As expected, the percentage dense area was the strongest risk factor for breast cancer in both groups. Conclusions Our results indicate that absolute dense area is independently and positively associated with breast cancer risk, whereas absolute nondense area is independently and inversely associated with breast cancer risk. Since adipose tissue is radiographically nondense, these results suggest that adipose breast tissue may have a protective role in breast carcinogenesis

Fibromuscular dysplasia presenting as a renal infarction: a case report

<p>Abstract</p> <p>Introduction</p> <p>Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory disease that most commonly affects the renal and internal carotid arteries.</p> <p>Case presentation</p> <p>We present the case of a 44-year-old Caucasian man who was admitted with complaints of loin pain and hypertension. A computed tomography scan of the abdomen revealed a right renal infarction with a nodular aspect of the right renal artery. Subsequent renal angiography revealed a typical 'string of beads' pattern of the right renal artery with thrombus formation. Oral anticoagulation was started and the secondary hypertension was easily controlled with anti-hypertensive drugs. At follow-up, our patient refused percutaneous transluminal renal angioplasty as a definitive treatment.</p> <p>Conclusions</p> <p>Fibromuscular dysplasia is the most common cause of renovascular hypertension in patients under 50 years of age. Presentation with renal infarction is rare.</p> <p>In fibromuscular dysplasia, angioplasty has been proven to have, at least for some indications, an advantage over anti-hypertensive drugs. Therefore, hypertension secondary to fibromuscular dysplasia is the most common cause of curable hypertension.</p