tbuckley/cabot-search huggingface dataset:
Plasma Sex Steroid Hormone Levels and Risk of Breast Cancer in Postmenopausal Women
Authors: Susan E. Hankinson, Walter C. Willett, JoAnn E. Manson, Graham A. Colditz, David J. Hunter, Donna Spiegelman, Robert L. Barbieri, Frank E. Speizer
Journal: JNCI Journal of the National Cancer Institute (1998)

A positive relationship has generally been observed between plasma estrogen levels and breast cancer risk in postmenopausal women, but most of these studies have been small and few have evaluated specific estrogen fractions (such as percent bioavailable estradiol). In addition, few studies have evaluated plasma androgen levels in relation to breast cancer risk, and their results have been inconsistent. We prospectively evaluated relationships between sex steroid hormone levels in plasma and risk of breast cancer in postmenopausal women by use of a case-control study nested within the Nurses' Health Study.Blood samples were collected during the period from 1989 through 1990. Among postmenopausal women not using hormone replacement therapy at blood collection (n = 11,169 women), 156 women were diagnosed with breast cancer after blood collection but before June 1, 1994. Two control subjects were selected per case subject and matched with respect to age, menopausal status, month and time of day of blood collection, and fasting status at the time of blood collection.From comparisons of highest and lowest (reference) quartiles, we observed statistically significant positive associations with risk of breast cancer for circulating levels of estradiol (multivariate relative risk [RR] = 1.91; 95% confidence interval [CI] = 1.06-3.46), estrone (multivariate RR = 1.96; 95% CI = 1.05-3.65), estrone sulfate (multivariate RR = 2.25; 95% CI = 1.23-4.12), and dehydroepiandrosterone sulfate (multivariate RR = 2.15; 95% CI = 1.11-4.17). We found no substantial associations with percent free or percent bioavailable estradiol, androstenedione, testosterone, or dehydroepiandrosterone. The positive relationships were substantially stronger among women with no previous hormone replacement therapy.Our data, in conjunction with past epidemiologic and animal studies, provide strong evidence for a causal relationship between postmenopausal estrogen levels and the risk of breast cancer.
Cancer Surveillance Series: Interpreting Trends in Prostate Cancer Part I: Evidence of the Effects of Screening in Recent Prostate Cancer Incidence, Mortality, and Survival Rates
Authors: B. F. Hankey, E. J. Feuer, L. X. Clegg, R. B. Hayes, J. M. Legler, P. C. Prorok, L. A. Ries, R. M. Merrill, R. S. Kaplan
Journal: JNCI Journal of the National Cancer Institute (1999)

The prostate-specific antigen test was approved by the U.S. Food and Drug Administration in 1986 to monitor the disease status in patients with prostate cancer and, in 1994, to aid in prostate cancer detection. However, after 1986, the test was performed on many men who had not been previously diagnosed with prostate cancer, apparently resulting in the diagnosis of a substantial number of early tumors. Our purpose is to provide insight into the effect of screening on prostate cancer rates. Detailed data are presented for whites because the size of the population allows for calculating statistically reliable rates; however, similar overall trends are seen for African-Americans and other races.Prostate cancer incidence data from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program and mortality data from the National Center for Health Statistics were analyzed.The following findings are consistent with a screening effect: 1) the recent decrease since 1991 in the incidence of distant stage disease, after not having been perturbed by screening; 2) the decline in the incidence of earlier stage disease beginning the following year (i.e., 1992); 3) the recent increases and decreases in prostate cancer incidence and mortality by age that appear to indicate a calendar period effect; and 4) trends in the incidence of distant stage disease by tumor grade and trends in the survival of patients with distant stage disease by calendar year that provide suggestive evidence of the tendency of screening to detect slower growing tumors.The decline in the incidence of distant stage disease holds the promise that testing for prostate-specific antigen may lead to a sustained decline in prostate cancer mortality. However, population data are complex, and it is difficult to confidently attribute relatively small changes in mortality to any one cause.
Very early screening of sleep-disordered breathing in acute coronary syndrome patients with preserved ventricular function
Authors: Sandra Van den Broecke, Olivier Jobard, Marie Bruyneel, Vincent Ninane, Isabelle Arnulf, Thomas Similowski, Valérie Attali
Journal: European Respiratory Journal (2013)

Introduction   Obstructive sleep apnea(OSA)is highly associated with acute coronary syndrome(ACS).This is the first study performing a very early screening of sleep-disordered breathing(SDB)in ACS patients with preserved ventricular function,using attended polygraphy(PV) and polysomnography(PSG),and comparing those methods.   Methods   27patients admitted forACS to the coronary care unit(CCU)were included.They underwent 1overnight attended sleep study at theCCU,within3days.A telemonitoring system was set up to remotely watch the recordings.Than,they were analysed in2different ways: PV&PSG.   Results   There were81%men with a left ventricular ejection fraction of48%.PSG/PV delay was2±1days and67%within48h.We found a high prevalence of SDB,mainly central and periodic breathing.  The telemonitoring system allowed successful interventions in48%of the recordings(80%for the nasal canula and 20%for the ground electrodes or oxymetry).   Conclusion   A very early screening of SDB,using attended PSG at the CCU is achievable.PSG exhibits a poor sleep efficiency in the majority of patients and allows a more precise evaluation of SDB severity.Surprisingly,in those patients with preserved ventricular function,we found a high prevalence of central apnea and periodic breathing.This results need to be more deeply investigated.
Managing the health of the elite athlete: a new integrated performance health management and coaching model
Authors: H Paul Dijkstra, N Pollock, R Chakraverty, J M Alonso
Journal: British Journal of Sports Medicine (2014)

Elite athletes endeavour to train and compete even when ill or injured. Their motivation may be intrinsic or due to coach and team pressures. The sports medicine physician plays an important role to risk-manage the health of the competing athlete in partnership with the coach and other members of the support team. The sports medicine physician needs to strike the right ethical and operational balance between health management and optimising performance. It is necessary to revisit the popular delivery model of sports medicine and science services to elite athletes based on the current reductionist multispecialist system lacking in practice an integrated approach and effective communication. Athlete and coach in isolation or with a member of the multidisciplinary support team, often not qualified or experienced to do so, decide on the utilisation of services and how to apply the recommendations. We propose a new Integrated Performance Health Management and Coaching model based on the UK Athletics experience in preparation for the London Olympic and Paralympic Games. The Medical and Coaching Teams are managed by qualified and experienced individuals operating in synergy towards a common performance goal, accountable to a Performance Director and ultimately to the Board of Directors. We describe the systems, processes and implementation strategies to assist the athlete, coach and support teams to continuously monitor and manage athlete health and performance. These systems facilitate a balanced approach to training and competing decisions, especially while the athlete is ill or injured. They take into account the best medical advice and athlete preference. This Integrated Performance Health Management and Coaching model underpinned the Track and Field Gold Medal performances at the London Olympic and Paralympic Games.
Effective inhibition of melanoma tumorigenesis and growth via a new complex vaccine based on NY-ESO-1-alum-polysaccharide-HH2
Authors: Meng Li, Huashan Shi, Yandong Mu, Zichao Luo, Hailong Zhang, Yang Wan, Dongmei Zhang, Lian Lu, Ke Men, Yaomei Tian, Xiaozhe Wu, Xiaoyan Liu, Ying Pan, Yingzi Fan, Chaoheng Yu, Bailing Zhou, Rong Xiang, Xiancheng Chen, Li Yang
Journal: Molecular Cancer (2014)

A safe and effective adjuvant plays an important role in the development of a vaccine. However, adjuvants licensed for administration in humans remain limited. Here, for the first time, we developed a novel combination adjuvant alum-polysaccharide-HH2 (APH) with potent immunomodulating activities, consisting of alum, polysaccharide of Escherichia coli and the synthetic cationic innate defense regulator peptide HH2. The adjuvant effects of APH were examined using NY-ESO-1 protein-based vaccines in prophylactic and therapeutic models. We further determined the immunogenicity and anti-tumor effect of NY-ESO-1-APH (NAPH) vaccine using adoptive cellular/serum therapy in C57/B6 and nude mice. Cell-mediated and antibody-mediated immune responses were evaluated. The APH complex significantly promoted antigen uptake, maturation and cross-presentation of dendritic cells and enhanced the secretion of TNF-α, MCP-1 and IFN-γ by human peripheral blood mononuclear cells compared with individual components. Vaccination of NAPH resulted in significant tumor regression or delayed tumor progression in prophylactic and therapeutic models. In addition, passive serum/cellular therapy potently inhibited tumor growth of NY-ESO-1-B16. Mice treated with NAPH vaccine produced higher antibody titers and greater antibody-dependent/independent cellular cytotoxicity. Therefore, NAPH vaccination effectively stimulated innate immunity, and boosted both arms of the adaptive humoral and cellular immune responses to suppress tumorigenesis and growth of melanoma. Our study revealed the potential application of APH complex as a novel immunomodulatory agent for vaccines against tumor refractory and growth.
Management of acute pancreatitis: from surgery to interventional intensive care
Authors: J Werner
Journal: Gut (2005)

In recent years, treatment of severe acute pancreatitis has shifted away from early surgical treatment to aggressive intensive care.While the treatment is conservative in the early phase, surgery might be considered in the later phase of the disease.Surgical debridement is still the ''gold standard'' for treatment of infected pancreatic and peripancreatic necrosis.Advances in radiological imaging, new developments in interventional radiology, and other minimal access interventions have revolutionised the management of many surgical conditions over the past decades.Several interventional therapy regimens, including endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy, fine needle aspiration for bacteriology (FNAB), percutaneous or endoscopic drainage of peripancreatic fluid collections, pseudocysts, and late abscesses, as well as selective angiography and catheter directed embolisation of acute pancreatitis associated bleeding complications have been well established as diagnostic and therapeutic standards in the management of acute pancreatitis.Secondary to recent technical improvements in interventional therapy and minimally invasive surgery, even infected pancreatic necrosis has successfully been treated in selected patients.However, technical feasibility does not obviate sound clinical judgement.We must be cautious in the application of new technologies in the absence of well designed clinical trials.Thus minimally invasive surgery and interventional therapy for infected necrosis should be limited to clinical trials and specific indications in patients who are critically ill and otherwise unfit for conventional surgery.
Endoplasmic Reticulum Stress As a Therapeutic Target in Cardiovascular Disease
Authors: Tetsuo Minamino, Issei Komuro, Masafumi Kitakaze
Journal: Circulation Research (2010)

Cardiovascular disease constitutes a major and increasing health burden in developed countries. Although treatments have progressed, the development of novel treatments for patients with cardiovascular diseases remains a major research goal. The endoplasmic reticulum (ER) is the cellular organelle in which protein folding, calcium homeostasis, and lipid biosynthesis occur. Stimuli such as oxidative stress, ischemic insult, disturbances in calcium homeostasis, and enhanced expression of normal and/or folding-defective proteins lead to the accumulation of unfolded proteins, a condition referred to as ER stress. ER stress triggers the unfolded protein response (UPR) to maintain ER homeostasis. The UPR involves a group of signal transduction pathways that ameliorate the accumulation of unfolded protein by increasing ER-resident chaperones, inhibiting protein translation and accelerating the degradation of unfolded proteins. The UPR is initially an adaptive response but, if unresolved, can lead to apoptotic cell death. Thus, the ER is now recognized as an important organelle in deciding cell life and death. There is compelling evidence that the adaptive and proapoptotic pathways of UPR play fundamental roles in the development and progression of cardiovascular diseases, including heart failure, ischemic heart diseases, and atherosclerosis. Thus, therapeutic interventions that target molecules of the UPR component and reduce ER stress will be promising strategies to treat cardiovascular diseases. In this review, we summarize the recent progress in understanding UPR signaling in cardiovascular disease and its related therapeutic potential. Future studies may clarify the most promising molecules to be investigated as targets for cardiovascular diseases.
In Situ Hybridization Reveals Extensive Diversity of K <sup>+</sup> Channel mRNA in Isolated Ferret Cardiac Myocytes
Authors: Mulugu V. Brahmajothi, Michael J. Morales, Shuguang Liu, Randall L. Rasmusson, Donald L. Campbell, Harold C. Strauss
Journal: Circulation Research (1996)

The molecular basis of K+ currents that generate repolarization in the heart is uncertain. In part, this reflects the similar functional properties different K+ channel clones display when heterologously expressed, in addition to the molecular diversity of the voltage-gated K+ channel family. To determine the identity, regional distribution, and cellular distribution of voltage-sensitive K+ channel mRNA subunits expressed in ferret heart, we used fluorescent labeled oligonucleotide probes to perform in situ hybridization studies on enzymatically isolated myocytes from the sinoatrial (SA) node, right and left atria, right and left ventricles, and interatrial and interventricular septa. The most widely distributed K+ channel transcripts in the ferret heart were Kv1.5 (present in 69.3% to 85.6% of myocytes tested, depending on the anatomic region from which myocytes were isolated) and Kv1.4 (46.1% to 93.7%), followed by kv1.2, Kv2.1, and Kv4.2. Surprisingly, many myocytes contain transcripts for Kv1.3, Kv2.2, Kv4.1, Kv5.1, and members of the Kv3 family. Kv1.1, Kv1.6, and Kv6.1, which were rarely expressed in working myocytes, were more commonly expressed in SA nodal cells. IRK was expressed in ventricular (84.3% to 92.8%) and atrial (52.4% to 64.0%) cells but was nearly absent (6.6%) in SA nodal cells; minK was most frequently expressed in SA nodal cells (33.7%) as opposed to working myocytes (10.3% to 29.3%). Two gene products implicated in long-QT syndrome, ERG and KvLQT1, were common in all anatomic regions (41.1% to 58.2% and 52.1% to 71.8%, respectively). These results show that the diversity of K+ channel mRNA in heart is greater than previously suspected and that the molecular basis of K+ channels may vary from cell to cell within distinct regions of the heart and also between major anatomic regions.
Comparison of coronary artery bypass surgery and percutaneous coronary intervention in patients with diabetes: a meta-analysis of randomised controlled trials
Authors: Subodh Verma, Michael E Farkouh, Bobby Yanagawa, David H Fitchett, Muhammad R Ahsan, Marc Ruel, Sachin Sud, Milan Gupta, Shantanu Singh, Nandini Gupta, Asim N Cheema, Lawrence A Leiter, Paul W M Fedak, Hwee Teoh, David A Latter, Valentin Fuster, Jan O Friedrich
Journal: The Lancet Diabetes & Endocrinology (2013)
TWO UNUSUAL CASES of FOREIGN BODIES REMOVED by the AID of the ROENTGEN RAYS
Authors: R. B. McCausland
Journal: BMJ (1898)

KIMICAL~~~~~~~~~~~~~~~~~~~~~~~~~J b"L occurred between the ages of io and 20 years, and in io cases the attack was the first.These patients were generally ad- mitted in extremis, with a history of from three to eight days' illness.The abdomen was opened in 8 cases, and ia the others the diagnosis was verified or made at the necropsy.In conclusion, taking all the cases together, the usual sym- ptoms were fairly constant.In 3 cases pain and swelling were more marked on the left side, and in 8 cases pain was complained of during micturition.Concretions were recorded in 12 instances (5 in Class c), and in I case the appendix came away as a slough three days after an abscess was opened.A faecal fistula resulted in 3 cases, and a ventral hernia in 2.
Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice?
Authors: Tito Livraghi, Franca Meloni, Michele Di Stasi, Emanuela Rolle, Luigi Solbiati, Carmine Tinelli, Sandro Rossi
Journal: Hepatology (2007)

If liver transplantation is not feasible, partial resection is considered the treatment of choice for hepatocellular carcinoma (HCC) in patients with cirrhosis. However, in some centers the first-line treatment for small, single, operable HCC is now radiofrequency ablation (RFA). In the current study, 218 patients with single HCC ≤ 2.0 cm (very early or T1 stage) underwent RFA. We assessed 2 primary end points that could be easily compared with those reported for resective surgery: (1) the rate of sustained, local, complete response and (2) the rate of treatment-related complications. The secondary end point was 5-year survival in the 100 patients whose tumors had been considered potentially operable. After a median follow-up of 31 months, sustained complete response was observed in 216 patients (97.2%). In the remaining 6, percutaneous ethanol injection, selective intraarterial chemoembolization, or resection were used as salvage therapy. Perioperative mortality, major complication, and 5-year survival rates were 0%, 1.8%, and 68.5%, respectively. Conclusion: Compared with resection, RFA is less invasive and associated with lower complication rate and lower costs. RFA is also just as effective for ensuring local control of stage T1 HCC, and it is associated with similar survival rates (as recently demonstrated by 2 randomized trials). These data indicate that RFA can be considered the treatment of choice for patients with single HCC ≤ 2.0 cm, even when surgical resection is possible. Other approaches can be used as salvage therapy for the few cases in which RFA is unsuccessful or unfeasible. (Hepatology 2007.)
The potential role of amyloid in the pathogenesis of age-related macular degeneration
Authors: T. Yoshida
Journal: Journal of Clinical Investigation (2005)

Drusen are extracellular deposits that lie beneath the retinal pigment epithelium (RPE) and are the earliest signs of age-related macular degeneration (AMD). Recent proteome analysis demonstrated that amyloid β (Aβ) deposition was specific to drusen from eyes with AMD. To work toward a molecular understanding of the development of AMD from drusen, we investigated the effect of Aβ on cultured human RPE cells as well as ocular findings in neprilysin gene–disrupted mice, which leads to an increased deposition Aβ. The results showed that Aβ treatment induced a marked increase in VEGF as well as a marked decrease in pigment epithelium-derived factor (PEDF). Conditioned media from Aβ-exposed RPE cells caused a dramatic increase in tubular formation by human umbilical vein endothelial cells. Light microscopy of senescent neprilysin gene–disrupted mice showed an increased number of degenerated RPE cells with vacuoles. Electron microscopy revealed basal laminar and linear deposits beneath the RPE layer, but we did not observe choroidal neovascularization (CNV). The present study demonstrates that Aβ accumulation affects the balance between VEGF and PEDF in the RPE, and an accumulation of Aβ reproduces features characteristic of human AMD, such as RPE atrophy and basal deposit formation. Some other factors, such as breakdown of integrity of Bruch membrane, might be necessary to induce CNV of AMD.
Physical activity in Dublin children aged 7–9 years
Authors: J Hussey, J Gormley, C Bell
Journal: British Journal of Sports Medicine (2001)

To investigate the amount of regular activity and time spent in sedentary occupations in children aged 7--9 years. Sex differences in levels of activity and time and facilities for physical education at school were also examined.A 10% sample of Dublin National Schools were selected. Parents of children in second class were surveyed. The questionnaire used was a modification of the Modifiable Activity Questionnaire for Adolescents. Teachers of second class were questioned about the time and facilities for physical education in schools.Some 39% of children were participating in hard exercise for at least 20 minutes three or more times a week, with fewer girls (28%) than boys (53%) contributing to this result. A further 57% of children were engaging in at least 20 minutes of light exercise three or more times a week, with no sex differences. Estimated energy expenditure in regular activity was higher in boys than girls. Most (78%) of the children were spending one to three hours a day sedentary in front of a screen.This study provides comprehensive data on physical activity levels in Dublin schoolchildren aged 7--9 years. The amount of inactivity is of concern. Even at this young age, boys are reported to participate in more physical activity than girls.