tbuckley/cabot-search huggingface dataset:
Capecitabine Plus Oxaliplatin Compared With Fluorouracil and Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer
Authors: Daniel G. Haller, Josep Tabernero, Jean Maroun, Filippo de Braud, Timothy Price, Eric Van Cutsem, Mark Hill, Frank Gilberg, Karen Rittweger, Hans-Joachim Schmoll
Journal: Journal of Clinical Oncology (2011)

This multicenter, randomized trial compared capecitabine plus oxaliplatin (XELOX) with bolus fluorouracil (FU) and folinic acid (FA) as adjuvant therapy for patients with stage III colon cancer.Patients who had undergone curative resection were randomly assigned to XELOX (oxaliplatin 130 mg/m(2) on day 1 plus capecitabine 1,000 mg/m(2) twice daily on days 1 to 14 every 3 weeks for 24 weeks) or a standard bolus FU/FA adjuvant regimen (Mayo Clinic for 24 weeks or Roswell Park for 32 weeks). The primary study end point was disease-free survival (DFS).The intention-to-treat population comprised 1,886 patients; 944 patients were randomly assigned to XELOX and 942 to FU/FA (Mayo Clinic, n = 664; Roswell Park, n = 278). After 57 months of follow-up for the primary analysis, 295 patients (31.3%) in the XELOX group had relapsed, developed a new primary colon cancer, or died compared with 353 patients (37.5%) in the FU/FA group (hazard ratio [HR] for DFS, 0.80; 95% CI, 0.69 to 0.93; P = .0045). The 3-year DFS rate was 70.9% with XELOX and 66.5% with FU/FA. The HR for overall survival (OS) for XELOX compared to FU/FA was 0.87 (95% CI, 0.72 to 1.05; P = .1486). The 5-year OS for XELOX and FU/FA were 77.6% and 74.2%, respectively. Follow-up is ongoing. Preplanned multivariate and subgroup analyses supported the robustness of these findings.The addition of oxaliplatin to capecitabine improves DFS in patients with stage III colon cancer. XELOX is an additional adjuvant treatment option for these patients.
US inches closer towards healthcare reform as houses prepare for debate
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

By early November the US Senate and the House of Representatives are likely to have pulled together several different bills on healthcare reform and to have begun debating them.

There are five bills, three in the House of Representatives and two in the Senate. Committees are working to come up with a single bill for each chamber. The House and the Senate bills may differ. 

The House and Senate will then debate each bill, propose amendments, and vote. After that a House and Senate conference committee will reconcile the bills, both House and Senate will vote on the final bill, and then send it to Barack Obama to sign or veto.

In the House, the bill can be passed by a simple majority, and Democrats have a large majority. In the Senate it will need 60 of the 100 senators to vote in favour, and that may be close. There are only 60 Democrats or those who vote with them in the Senate. Democrats in the House and Senate disagree among themselves about the proposed reforms (www.washingtonpost.com, 17 Oct 2009, “House, Senate Dems at odds over health care overhaul”).

Tom Harkin, senator and Iowa Democrat, told the Bloomberg news service that he expected the Senate bill to be finished before …
Effect of Intensive Lipid Lowering, With or Without Antioxidant Vitamins, Compared With Moderate Lipid Lowering on Myocardial Ischemia in Patients With Stable Coronary Artery Disease
Authors: Peter H. Stone, Donald M. Lloyd-Jones, Scott Kinlay, Balz Frei, William Carlson, Joel Rubenstein, Thomas C. Andrews, Michael Johnstone, George Sopko, Holly Cole, John Orav, Andrew P. Selwyn, Mark A. Creager
Journal: Circulation (2005)

Lipid lowering with statins prevents adverse cardiac events. Both lipid-lowering and antioxidant therapies may favorably affect vasomotor function and thereby improve ischemia.In a randomized, double-blind, placebo-controlled trial, 300 patients with stable coronary disease, a positive exercise treadmill test, 48-hour ambulatory ECG with > or =1 episode of ischemia, and fasting total cholesterol of 180 to 250 mg/dL were assigned to 1-year treatment with intensive atorvastatin to reduce LDL to <80 mg/dL (n=96), intensive atorvastatin to reduce LDL to <80 mg/dL plus antioxidant vitamins C (1000 mg/d) and E (800 mg/d) (n=101), or diet and low-dose lovastatin, if needed, to reduce LDL to <130 mg/dL (n=103; control group). Ischemia end points, including ambulatory ECG monitoring and exercise treadmill testing, and endothelial assessment using brachial artery flow-mediated dilation were obtained at baseline and at 6 and 12 months. Baseline characteristics were similar in all groups. LDL decreased from approximately 153 mg/dL at baseline in the 2 atorvastatin groups to approximately 83 mg/dL at 12 months (each P<0.0001) and from 147 to 120 mg/dL in the control group (P<0.0001). During ambulatory ECG monitoring, mean number of ischemic episodes per 48 hours decreased 31% to 61% in each group (each P<0.001; P=0.15 across groups), without a change in daily heart rate activity. Mean duration of ischemia for 48 hours decreased 26% to 62% in each group (each P<0.001; P=0.06 across groups). Mean exercise duration to 1-mm ST-segment depression significantly increased in each group, but total exercise duration and mean sum of maximum ST depression were unchanged. Angina frequency decreased in each group. There was no incremental effect of supplemental vitamins C and E on any ischemia outcome. Flow-mediated dilation studies indicated no meaningful changes.Intensive lipid lowering with atorvastatin to an LDL level of 80 mg/dL, with or without antioxidant vitamins, does not provide any further benefits in ambulatory ischemia, exercise time to onset of ischemia, and angina frequency than moderate lipid lowering with diet and low-dose lovastatin to an LDL level of <120 mg/dL.
Incretins and Amylin: Neuroendocrine Communication Between the Gut, Pancreas, and Brain in Control of Food Intake and Blood Glucose
Authors: Matthew R. Hayes, Elizabeth G. Mietlicki-Baase, Scott E. Kanoski, Bart C. De Jonghe
Journal: Annual Review of Nutrition (2014)

Arguably the most fundamental physiological systems for all eukaryotic life are those governing energy balance. Without sufficient energy, an individual is unable to survive and reproduce. Thus, an ever-growing appreciation is that mammalian physiology developed a redundant set of neuroendocrine signals that regulate energy intake and expenditure, which maintains sufficient circulating energy, predominantly in the form of glucose, to ensure that energy needs are met throughout the body. This orchestrated control requires cross talk between the gastrointestinal tract, which senses the incoming meal; the pancreas, which produces glycemic counterregulatory hormones; and the brain, which controls autonomic and behavioral processes regulating energy balance. Therefore, this review highlights the physiological, pharmacological, and pathophysiological effects of the incretin hormones glucagon-like peptide-1 and gastric inhibitory polypeptide, as well as the pancreatic hormone amylin, on energy balance and glycemic control.
Fat and female fecundity: prospective study of effect of body fat distribution on conception rates.
Authors: B M Zaadstra, J C Seidell, P A Van Noord, E R te Velde, J D Habbema, B Vrieswijk, J Karbaat
Journal: BMJ (1993)

To study the effect of body fat distribution in women of reproductive age on fecundity.Prospective cohort study of all women who had entered a donor insemination programme.One fertility clinic serving a large part of the midwest of the Netherlands.Of 542 women attending the clinic for artificial insemination for the first time, 500 women were eligible for study.Probability of conception per cycle and number of insemination cycles before pregnancy or stopping treatment.A 0.1 unit increase in waist-hip ratio led to a 30% decrease in probability of conception per cycle (hazard ratio 0.706; 95% confidence interval 0.562 to 0.887) after adjustment for age, fatness, reasons for artificial insemination, cycle length and regularity, smoking, and parity. Increasing age was significantly related to lower fecundity (p < 0.05); very lean and obese women were less likely to conceive (p < 0.10) as were women with subfertile partners (p < 0.10). All other exposure variables were not significantly related to fecundity.Increasing waist-hip ratio is negatively associated with the probability of conception per cycle, before and after adjustment for confounding factors. Body fat distribution in women of reproductive age seems to have more impact on fertility than age or obesity.
Tranilast Inhibits Vascular Smooth Muscle Cell Growth and Intimal Hyperplasia by Induction of p21 <sup>waf1/cip1/sdi1</sup> and p53
Authors: Akihiro Takahashi, Takahiro Taniguchi, Yuichi Ishikawa, Mitsuhiro Yokoyama
Journal: Circulation Research (1999)

Tranilast, which is an antiallergic drug, has a potent effect on preventing postangioplasty restenosis. To elucidate this mechanism, we studied the effect of tranilast on the proliferation of vascular smooth muscle cells (SMCs) in vitro and in vivo. Tranilast decreased the growth rate of SMCs stimulated by either 10% FBS or platelet-derived growth factor. The IC50 value, evaluated as cell number, was 100 micromol/L. These inhibitory effects were associated with inhibition of the retinoblastoma gene product (pRb) phosphorylation. Because pRb phosphorylation is regulated by cyclin-dependent kinases (CDK), we investigated CDK2 and CDK4 activities and the expression of CDK inhibitor p21(waf1/cip1/sdi1) (p21). When SMCs were stimulated by 10% FBS or platelet-derived growth factor, CDK2 and CDK4 activities reached a maximum near the G1/S transition. Tranilast suppressed their activities by >80% without reduction of CDK2/cyclin E and CDK4/cyclin D1 protein levels. These inhibitory effects were associated with enhanced expression of p21 and elevated complexing of p21 with CDK2/CDK4. Next, rat balloon-injured carotid artery was analyzed for intimal thickening and p21 expression. Tranilast-treated rats had a 70% (P<0.001) smaller neointima/media area ratio at 14 days after balloon injury compared with the controls. Immunohistochemical staining demonstrated that, in tranilast-treated rats, p21 was already present in the neointima at day 7 and strongly expressed throughout the neointima at day 14. In control rats, p21 was not observed in the neointima at day 7 but was sparsely expressed at day 14. These data demonstrate that inhibition of CDK2/CDK4 activities by the increased expression of p21 may be one mechanism by which tranilast inhibits SMC proliferation and prevents postangioplasty restenosis.
Effects on small-intestinal function and structure induced by feeding a deconjugated bile salt
Authors: M. Gracey, J. Papadimitriou, V. Burke, J. Thomas, G. Bower
Journal: Gut (1973)

Feeding sodium deoxycholate orally to rats for three days caused inhibition of small-intestinal active sugar transport and ouabain-sensitive, sodium-potassium-dependent adenosine triphosphatase activity. At the same time, there was evidence of extensive ultrastructural damage to the microvillar and intracellular compartments of the small-intestinal epithelium while its light microscopic appearance was essentially normal. These functional and morphological changes reverted towards normal over the subsequent four days when a normal diet, without added bile salt, was reintroduced.
Predictors of outcomes in COPD exacerbation cases presenting to the emergency department
Authors: N. Roche, M. Zureik, D. Soussan, F. Neukirch, D. Perrotin
Journal: European Respiratory Journal (2008)

The aim of the present prospective multicentric study was to develop a simple rule for the prediction of poor outcome in patients presenting to emergency departments with initially non-life threatening-chronic obstructive pulmonary disease (COPD) exacerbations in a real-life setting. All patients with an acute exacerbation of COPD visiting the emergency departments of 103 hospitals during a 3-month period were included, except those who immediately required intensive care unit admission and/or ventilatory support. The data collected included patient characteristics, in-hospital outcomes (mortality and length of stay) and mode of discharge (unsupported or need for post-hospital assistance). The in-hospital mortality rate was 7.4% (59 out of 794). Independent prognostic factors were age, number of clinical signs of severity (among cyanosis, impaired neurological status, lower limb oedema, asterixis and use of accessory inspiratory or expiratory muscles) and dyspnoea grade in the stable state. The need for post-hospital support was also predicted by female sex. In order to construct and validate a prediction score for mortality based on these items, patients were randomly allocated to a derivation and a validation cohort. The prediction score showed good discrimination, with a c-statistic of 0.79 in the derivation cohort and 0.83 in the validation cohort. Thus simple purely clinical factors can reliably predict the risk of death and requirement for post-hospital support in an initially non-life threatening-acute exacerbation of chronic obstructive pulmonary disease. Their use needs to be prospectively validated.
Localization of a Prostate Cancer Predisposition Gene to an 880-kb Region on Chromosome 22q12.3 in Utah High-Risk Pedigrees
Authors: Nicola J. Camp, James M. Farnham, Lisa A. Cannon-Albright
Journal: Cancer Research (2006)

Chromosome 22q has become recently a region of interest for prostate cancer. We identified previously a logarithm of odds (LOD) of 2.42 at chromosome 22q12.3. Additionally, this region has been noted by eight other studies, with linkage evidence ranging from LOD of 1.50 to 3.57. Here, we do fine mapping and localization of the region using a pedigree-specific recombinant mapping approach in 14 informative, high-risk Utah pedigrees. These 14 pedigrees were chosen because they were either "linked" or "haplotype-sharing" pedigrees or both. "Linked" pedigrees were those with significant pedigree-specific linkage evidence (LOD, >0.588; P < 0.05) to the 22q12.3 region, regardless of the number of prostate cancer cases sharing the segregating haplotype. "Haplotype-sharing" pedigrees were those with at least five prostate cancer cases sharing a segregating haplotype in the 22q12.3 region, regardless of the linkage evidence. In each pedigree, the most likely haplotype configuration (in addition to the multipoint LOD graph for linked pedigrees) was used to infer the position of recombinant events and delimit the segregating chromosomal segment in each pedigree. These pedigree-specific chromosomal segments were then overlaid to form a consensus recombinant map across all 14 pedigrees. Using this method, we identified a 881,538-bp interval at 22q12.3, between D22S1265 and D22S277, which is the most likely region that contains the 22q prostate cancer predisposition gene. The unique Utah extended high-risk pedigree resource allows this powerful localization approach in pedigrees with evidence for segregating predisposition to prostate cancer. We are mutation screening candidate genes in this region to identify specific genetic variants segregating in these pedigrees.
Economic Implications of Increased Longevity in the United States
Authors: Dorothy P. Rice, Norman Fineman
Journal: Annual Review of Public Health (2004)

The elderly population in America is growing in size owing to declining death rates, increasing life expectancy, and the aging of the baby boomers. Although the prevalence of chronic illness and disability increases with age, successful aging in the elderly population is widespread, and the elderly are generally healthy. Indeed, the prevalence of disability among the elderly is declining, and expenditures for their care are increasingly concentrated at the end of life rather than during extra years of relatively healthy life. Nevertheless, health care costs will undoubtedly increase during the next 30 years as a result of the baby boomers entering late life. The economic and social impact of future growing health care expenditures for the elderly will be significant. Important policy issues will include the continued viability of the Medicare and Social Security programs, future needs for long-term care, improvement of the health status of the elderly, technological advances, the need for a geriatric work force, and development of viable strategies to pay for escalating medical care costs.
Lung Cancer Among Postmenopausal Women Treated With Estrogen Alone in the Women's Health Initiative Randomized Trial
Authors: Rowan T. Chlebowski, Garnet L. Anderson, JoAnn E. Manson, Ann G. Schwartz, Heather Wakelee, Margery Gass, Rebecca J. Rodabough, Karen C. Johnson, Jean Wactawski-Wende, Jane Morley Kotchen, Judith K. Ockene, Mary Jo O'Sullivan, F. Allan Hubbell, Jason W. Chien, Chu Chen, Marcia L. Stefanick
Journal: JNCI Journal of the National Cancer Institute (2010)

In the Women's Health Initiative (WHI) randomized controlled trial, use of estrogen plus progestin increased lung cancer mortality. We conducted post hoc analyses in the WHI trial evaluating estrogen alone to determine whether use of conjugated equine estrogen without progestin had a similar adverse influence on lung cancer.
Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial
Authors: Jonas Bergh, Tom Wiklund, Björn Erikstein, Elisabet Lidbrink, Henrik Lindman, Per Malmström, Pirkko Kellokumpu-Lehtinen, Nils-Olof Bengtsson, Gustaf Söderlund, Gun Anker, Erik Wist, Susanne Ottosson, Eeva Salminen, Per Ljungman, Harald Holte, Jonas Nilsson, Carl Blomqvist, Nils Wilking
Journal: The Lancet (2000)
A reappraisal of brush cytology for screening of Barrett’s esophagus
Authors: A. Pacha, K. Krishnadath
Journal: Endoscopy (2010)

Barrett’s esophagus is defined as a condition in which normal squamous epithelium of the distal esophagus is replaced by incomplete intestinalized columnar epithelium [1]. This change of the metaplastic esophageal epithelium to a columnar type of epithelium is viewed as a complication of excessive esophageal mucosal damage caused by symptomatic or asymptomatic gastroesophageal reflux disease (GERD) [2] [3]. It is appreciated that generally a subset of patients with severe reflux-induced esophagitis develops metaplastic columnar epithelium and even a smaller group of these patients eventually develop dysplasia, and finally, at the top of the large iceberg, a very small number would go on to develop high grade dysplasia or esophageal adenocarcinoma (EAC). The most common risk factor for EAC is chronic GERD, which is associated with an approximately 16-fold increased risk of developing EAC, and occurs in as many as 60 % of patients in whom this tumor is diagnosed. The risk of developing EAC in patients with Barrett’s esophagus appears to be approximately 30 – 125-fold greater than that in the general population, with an estimated incidence of 1 in 18 patient years [2] [3].
Enhanced Phagocytic Capacity THE BIOLOGIC BASIS FOR THE ELEVATED HISTOCHEMICAL NITROBLUE TETRAZOLIUM REACTION
Authors: Charles E. McCall, Lawrence R. DeChatelet, Robert Butler, David Brown
Journal: Journal of Clinical Investigation (1974)

The biologic basis for the elevated histochemical reduction of nitroblue tetrazolium dye (NBT) in neutrophils from patients with acute bacterial infection or polycythemia vera was studied. A precipitin reaction followed mixing NBT with heparin. NBT was reduced after phagocytosis of this complex (H-NBT) by polymorphonuclear leukocytes (PMNs). Ingestion required divalent cations and was facilitated by the presence of complement. H-NBT incubated with normal but not with C2-deficient human serum converted native C3 to its inactive form.
apoE isoform–specific disruption of amyloid β peptide clearance from mouse brain
Authors: Rashid Deane, Abhay Sagare, Katie Hamm, Margaret Parisi, Steven Lane, Mary Beth Finn, David M. Holtzman, Berislav V. Zlokovic
Journal: Journal of Clinical Investigation (2008)

Neurotoxic amyloid β peptide (Aβ) accumulates in the brains of individuals with Alzheimer disease (AD). The APOE4 allele is a major risk factor for sporadic AD and has been associated with increased brain parenchymal and vascular amyloid burden. How apoE isoforms influence Aβ accumulation in the brain has, however, remained unclear. Here, we have shown that apoE disrupts Aβ clearance across the mouse blood-brain barrier (BBB) in an isoform-specific manner (specifically, apoE4 had a greater disruptive effect than either apoE3 or apoE2). Aβ binding to apoE4 redirected the rapid clearance of free Aβ40/42 from the LDL receptor–related protein 1 (LRP1) to the VLDL receptor (VLDLR), which internalized apoE4 and Aβ-apoE4 complexes at the BBB more slowly than LRP1. In contrast, apoE2 and apoE3 as well as Aβ-apoE2 and Aβ-apoE3 complexes were cleared at the BBB via both VLDLR and LRP1 at a substantially faster rate than Aβ-apoE4 complexes. Astrocyte-secreted lipo-apoE2, lipo-apoE3, and lipo-apoE4 as well as their complexes with Aβ were cleared at the BBB by mechanisms similar to those of their respective lipid-poor isoforms but at 2- to 3-fold slower rates. Thus, apoE isoforms differentially regulate Aβ clearance from the brain, and this might contribute to the effects of APOE genotype on the disease process in both individuals with AD and animal models of AD.
Novel Model of Constrictive Pericarditis Associated With Autoimmune Heart Disease in Interferon-γ–Knockout Mice
Authors: Marina Afanasyeva, Dimitrios Georgakopoulos, DeLisa Fairweather, Patrizio Caturegli, David A. Kass, Noel R. Rose
Journal: Circulation (2004)

Constrictive pericarditis represents a serious hemodynamic syndrome that may lead to heart failure. Studies of its pathophysiological mechanisms have been impeded by the lack of an animal model.Cardiac myosin-induced experimental autoimmune myocarditis in interferon (IFN)-gamma-knockout (KO) mice results in increased cardiac inflammation and development of severe grossly detectable pericarditis. Using in vivo pressure-volume studies, we found that the acute phase of experimental autoimmune myocarditis in IFN-gamma-KO mice was characterized by reduced left ventricular (LV) volumes compared with wild-type mice. The KO mice exhibited a classic restrictive/constrictive phenotype with decreased cardiac output, increased chamber stiffness, preserved ejection fraction, and impaired diastolic filling, characterized by reduced deceleration time and pressure tracings showing the square root sign similar to that observed in clinical cases of constrictive pericarditis. This phenotype was not associated with the severity of myocarditis but correlated with the presence of grossly detectable adhesive pericarditis present only in the KO group and characterized by increased pericardial inflammation and fibrosis. Comparison of IFN-gamma-KO and wild-type mice matched for the severity of myocardial disease further confirmed that pericarditis, and not myocarditis, was responsible for smaller LV volumes, reduced cardiac output, increased cardiac stiffness, and increased peak filling rate adjusted for end-diastolic volumes in KO mice.Autoimmune heart disease in IFN-gamma-KO mice results in increased pericardial inflammation and fibrosis, leading to constrictive phenotype during the acute phase of disease. It represents a novel animal model of constrictive pericarditis.