tbuckley/cabot-search huggingface dataset:
Phase I Trial and Pharmacokinetic Study of Pemetrexed in Children With Refractory Solid Tumors: The Children's Oncology Group
Authors: Suman Malempati, H. Stacy Nicholson, Joel M. Reid, Susan M. Blaney, Ashish M. Ingle, Mark Krailo, Linda C. Stork, Allen S. Melemed, Renee McGovern, Stephanie Safgren, Matthew M. Ames, Peter C. Adamson
Journal: Journal of Clinical Oncology (2007)

Purpose We report results of a phase I trial and pharmacokinetic study of pemetrexed (LY231514) in children and adolescents with refractory solid tumors. Pemetrexed is a novel antifolate that inhibits multiple enzymes necessary for the biosynthesis of thymidine and purine nucleotides. The purpose of this study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetic properties of pemetrexed in children. Patients and Methods Pemetrexed was administered as a 10-minute intravenous infusion every 21 days. Patients received vitamin B 12 and folic acid supplementation as well as dexamethasone prophylaxis. Cohorts of three to six children were enrolled at dose levels of 400, 520, 670, 870, 1,130, 1,470, 1,910, and 2,480 mg/m 2 . Pharmacokinetic studies were performed during the first course of treatment. Results Thirty-three patients (31 assessable) with a median age of 12 years were enrolled. DLT occurred in one of six patients at 1,470 mg/m 2 and two of four patients at 2,480 mg/m 2 . The MTD was 1,910 mg/m 2 . The primary DLTs were neutropenia and rash. No objective antitumor responses were seen. Mean plasma clearance, half-life, and steady-state volume of distribution values were 2.3 L/h/m 2 , 2.5 hours, and 5.4 L/m 2 , respectively. Conclusion Pemetrexed is well-tolerated in children with refractory solid tumors at doses similar to the MTD in adults. The recommended dose for phase II studies is 1,910 mg/m 2 administered every 21 days with dexamethasone, folic acid, and vitamin B 12 supplementation.
Vascular complications in living related liver transplantation detected with intraoperative and postoperative Doppler US
Authors: Hitoshi Someda, Fuminori Moriyasu, Masazumi Fujimoto, Noriyuki Hamato, Motoshige Nabeshima, Koji Nishikawa, Minoru Okuma, Koichi Tanaka, Kazue Ozawa
Journal: Journal of Hepatology (1995)
Diathesis stress model or “Just So” story?
Authors: Richard M. McFall, James T. Townsend, Richard J. Viken
Journal: Behavioral and Brain Sciences (1995)

Abstract Mealey's sociopathy model is an exemplar of popular diathesis-stress models. Although such models, when presented in descriptive language, offer the illusion of integrative explanation, their actual scientific value is very limited because they fail to make specific, quantitative, falsifiable predictions. Conceptual and quantitative weaknesses of such diathesis-stress models are discussed and the requirements for useful models are outlined.
Demonstration of 2-hydroxybenzoylglycine as a drug binding inhibitor in newborn infants.
Authors: B Suh, S J Wadsworth, D M Lichtenwalner
Journal: Journal of Clinical Investigation (1987)

Newborn infants have drug binding defects that share similarities to those of uremic subjects. Since 2-hydroxybenzoylglycine has been chemically defined to be a major drug binding inhibitor in uremia, a search for the presence of a similar compound in the sera of newborn infants was made. An organic substance that has the characteristics of 2-hydroxybenzoylglycine as supported by the retardation factor values on thin-layer chromatograms, retention times of high performance liquid chromatograms, fluorescence emission spectra, and mass spectrum has been demonstrated to be present in the majority of the neonatal sera studied. A strong positive correlation between the levels of the binding inhibitor and the extent of binding defects for nafcillin has been observed. The substance could effectively reduce the total bilirubin concentration when added to the cord sera specimens. It is concluded that 2-hydroxybenzoylglycine plays an important role in drug binding defects observed in the newborn, and the inhibitor may also play a part in the precipitation of bilirubin-induced neurotoxicity in neonates when the substance is abnormally elevated.
Inhaled Corticosteroids and the Risk of Mortality and Readmission In Elderly Patients with Chronic Obstructive Pulmonary Disease
Authors: DON D. SIN, JACK V. TU
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

There is considerable controversy concerning the utility of inhaled corticosteroids for the long-term treatment of patients with COPD. Recent studies have suggested that although inhaled corticosteroids do not alter the rate of decline in lung function, they may reduce airway hyperresponsiveness, decrease the frequency of exacerbations, and slow the rate of decline in the patients' health status. The relationship between inhaled corticosteroids and subsequent risk of hospitalization or mortality remains unknown. We therefore conducted a population-based cohort study using administrative databases in Ontario, Canada (n = 22,620) to determine the association between inhaled corticosteroid therapy and the combined risk of repeat hospitalization and all-cause mortality in elderly patients with COPD. Patients who received inhaled corticosteroid therapy postdischarge (within 90 d) had 24% fewer repeat hospitalizations for COPD (95% confidence interval [CI], 22 to 35%) and were 29% less likely to experience mortality (95% CI, 22 to 35%) during 1 yr of follow-up after adjustment for various confounding factors. This cohort study has suggested that inhaled corticosteroid therapy is associated with reduced COPD-related morbidity and mortality in elderly patients. Although not definitive, because of the observational nature of these findings, these data provide a compelling rationale for a large randomized trial to determine the effect of inhaled corticosteroids on COPD-related morbidity and mortality.Keywords: chronic obstructive pulmonary disease; inhaled corticosteroids; hospitalization; mortality
Urinary NGAL Marks Cystic Disease in HIV-Associated Nephropathy
Authors: Neal Paragas, Thomas L. Nickolas, Christina Wyatt, Catherine S. Forster, Meghan Sise, Susan Morgello, Bernd Jagla, Charles Buchen, Peter Stella, Simone Sanna-Cherchi, Maria Luisa Carnevali, Silvia Mattei, Achiropita Bovino, Lucia Argentiero, Andrea Magnano, Prasad Devarajan, Kai M. Schmidt-Ott, Landino Allegri, Paul Klotman, Vivette D'Agati, Ali G. Gharavi, Jonathan Barasch
Journal: Journal of the American Society of Nephrology (2009)

Nephrosis and a rapid decline in kidney function characterize HIV-associated nephropathy (HIVAN). Histologically, HIVAN is a collapsing focal segmental glomerulosclerosis with prominent tubular damage. We explored the expression of neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular injury, to determine whether this protein has the potential to aid in the noninvasive diagnosis of HIVAN. We found that expression of urinary NGAL was much higher in patients with biopsy-proven HIVAN than in HIV-positive and HIV-negative patients with other forms of chronic kidney disease. In the HIV-transgenic mouse model of HIVAN, NGAL mRNA was abundant in dilated, microcystic segments of the nephron. In contrast, urinary NGAL did not correlate with proteinuria in human or in mouse models. These data show that marked upregulation of NGAL accompanies HIVAN and support further study of uNGAL levels in large cohorts to aid in the noninvasive diagnosis of HIVAN and screen for HIVAN-related tubular damage.
Infusion of trastuzumab maintenance doses over 30 minutes
Authors: A. Ring, R. Simcock, S. Mitra, D. Bloomfield, J. King, S. Simpson, G. Sadler, A. Webb
Journal: Annals of Oncology (2008)

The humanized monoclonal antibody trastuzumab is licensed for both the adjuvant treatment of early breast cancer and the palliation of metastatic breast cancer [1]. In the UK, trastuzumab is usually administered on a three weekly schedule. According to the license, it is infused over a period of 90 min and the patient is observed for 4.5 h after the loading dose, and for 30 min after all subsequent maintenance infusions. Prolonged infusion times have been justified by the risk of infusion reactions, with 54% of patients having at least one symptom with their first infusion, usually pyrexia, headache or rigors [2].
BMA tells doctors to take career breaks working in world's poorest countries
Authors: Adrian O'Dowd
Journal: BMJ (2007)

British doctors should consider volunteering their time to work abroad to help improve the health of poor people overseas, a new BMA report says.

The report on the health of the world's poor, which was published this week, says that the NHS should actively support health improvements in poor countries.

The United Kingdom, which has recruited many thousands of health workers from poor countries in the past decade without incurring training costs (Observations, doi: 10.1136/bmj.39206.640903.94), has a duty to assist financially poor countries to rebuild their …
Large-scale test of hypothesised associations between the angiotensin-converting-enzyme insertion/deletion polymorphism and myocardial infarction in about 5000 cases and 6000 controls
Authors: Bernard Keavney, Colin McKenzie, Sarah Parish, Alison Palmer, Sarah Clark, Linda Youngman, Marc Delépine, Mark Lathrop, Richard Peto, Rory Collins
Journal: The Lancet (2000)
Whipple's endocarditis
Authors: D West, S Hutcheon, R Kain, T Reid, S Walton, K Buchan
Journal: Journal of the Royal Society of Medicine (2005)

The causal organism in Whipple's disease, a rare disorder with characteristic duodenal and jejunal changes, was first cultured in 2000.1 Although cardiac involvement is common in Whipple's, it is seldom an isolated finding.
Genome-Wide CpG Island Profiling of Intraductal Papillary Mucinous Neoplasms of the Pancreas
Authors: Seung-Mo Hong, Noriyuki Omura, Audrey Vincent, Ang Li, Spencer Knight, Jun Yu, Ralph H. Hruban, Michael Goggins
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Intraductal papillary mucinous neoplasms (IPMN) are precursors to infiltrating pancreatic ductal adenocarcinomas. Widespread epigenetic alterations are characteristic of many cancers, yet few studies have systematically analyzed epigenetic alterations of neoplastic precursors. Our goal was to conduct genome-wide CpG island methylation profiling to identify aberrantly methylated loci in IPMNs. Experimental Design: We compared the CpG island methylation profiles of six IPMNs to normal primary pancreatic duct samples using methylation CpG island amplification (MCA) and Agilent CpG island microarray (MCAM) analysis. When selected 13 genes identified as differentially methylated by MCAM for methylation-specific PCR (MSP) analysis in an independent set of IPMNs and normal pancreas samples and conducted expression analysis of selected genes. Results: We identified 2,259 loci as differentially methylated in at least one of six IPMNs including 245 genes hypermethylated in IPMNs with high-grade dysplasia compared with normal pancreatic duct samples. Eleven of 13 genes evaluated by MSP were more commonly methylated in 61 IPMNs than in 43 normal pancreas samples. Several genes (BNIP3, PTCHD2, SOX17, NXPH1, EBF3) were significantly more likely to be methylated in IPMNs with high-grade than with low-grade dysplasia. One gene, SOX17, showed loss of protein expression by immunohistochemistry in 22% (19 of 88) of IPMNs. The most specific marker, BNIP3, was not methylated in any IPMNs with low-grade dysplasia or in normal pancreas samples. Conclusions: IPMNs undergo extensive aberrant CpG island hypermethylation. The detection of genes selectively methylated in high-grade IPMNs such as BNIP3 may have use in the clinical evaluation of IPMNs. Clin Cancer Res; 18(3); 700–12. ©2011 AACR.
Do patients with COPD benefit from treatment with inhaled corticosteroids?
Authors: CP van Schayck, PM van Grunsven, PN Dekhuijzen
Journal: European Respiratory Journal (1996)

In the past few years, treatment with inhaled corticosteroids has become increasingly important in asthma [1, 2]. It appears that inflammation of the airway wall is a major pathophysiological mechanism underlying asthma [3], and perhaps also chronic obstructive pulmonary disease (COPD) [4]. Some long-term studies in asthmatic patients over 1 and 2 yrs have shown that maintenance treatment with inhaled corticosteroids is beneficial [5‐ 7]. In contrast to asthma, the efficacy and therefore the precise role of inhaled corticosteroids is less clear in the treatment of patients with COPD [8, 9]. Corticosteroids are generally given in COPD, in order to treat exacerbations, for a relatively short period of time. The efficacy of long-term treatment with inhaled steroids is not yet established. Whilst in asthma the response is rapid, there are indications that (some) patients with COPD may only respond adequately to (oral) corticosteroids after 6 months to 2 yrs of therapy [10]. We have, therefore, investigated the literature over the past 15 yrs on short-term as well as long-term response to inhaled steroids in COPD. This was done by means of a Medline Search (MeSH headings and/or free text words: antiinflammatory-agents-steroidal; chronic airflow obstruction; COPD-chronic obstructive pulmonary disease). Only randomized controlled studies (English-written) with inhaled steroids were included. Special attention was paid to possible predictors of a long-term response to inhaled steroids in COPD.
Secretion of pyruvate. An antioxidant defense of mammalian cells.
Authors: J O'Donnell-Tormey, C F Nathan, K Lanks, C J DeBoer, J de la Harpe
Journal: The Journal of Experimental Medicine (1987)

Cells in culture are exposed to marked oxidative stress, H2O2 being one of the predominant agents. Pyruvate and other alpha-ketoacids reacted rapidly, stoichiometrically, and nonenzymatically with H2O2, and they protected cells from its cytolytic effects. All five human and murine cell types studied, both malignant and nonmalignant, released pyruvate at an initial rate of 35-60 microM/h/2.5 X 10(6) cells when placed in 1 ml pyruvate-free medium. After 6-12 h a plateau of 60-150 microM pyruvate was attained, corresponding to concentrations reported for normal human serum and plasma. The rate of pyruvate accumulation was almost doubled in the presence of exogenous catalase, suggesting that released pyruvate functions as an antioxidant. The rate of pyruvate accumulation was dependent on cell number. Succinate, fumarate, citrate, oxaloacetate, alpha-ketoglutarate, and malate were not secreted in significant amounts from P815 cells; export was specific for pyruvate and lactate among the metabolites tested. Extracellular pyruvate was in equilibrium with intracellular stores. Thus, cells conditioned the extracellular medium with pyruvate at the expense of intracellular pyruvate, until homeostatic levels were attained in both compartments. We propose that cells plated at low density in the absence of exogenous pyruvate fail to thrive for two reasons: prolonged depletion of intracellular pyruvate and prolonged vulnerability to oxidant stress.
Two geographically separated food-borne outbreaks in Sweden linked by an unusual Cryptosporidium parvum subtype, October 2010
Authors: A Gherasim, M Lebbad, M Insulander, V Decraene, A Kling, M Hjertqvist, A Wallensten
Journal: Eurosurveillance (2012)

Binary file ES_Abstracts_Final_ECDC.txt matches
Dendritic and Natural Killer Cells Cooperate in the Control/Switch of Innate Immunity
Authors: Laurence Zitvogel
Journal: The Journal of Experimental Medicine (2002)

Twenty years ago, R. Steinman and colleagues established that dendritic cells (DCs) have unique capacities to prime naive T cells and that DC maturation is the checkpoint for the initiation of adaptive immune responses ([1][1]–[3][2]). In the mid-1990s, C. Janeway pointed out the pivotal role of
ACC/AHA/SCAI 2014 Health Policy Statement on Structured Reporting for the Cardiac Catheterization Laboratory
Authors: Timothy A. Sanborn, James E. Tcheng, H. Vernon Anderson, Charles E. Chambers, Sharon L. Cheatham, Matthew V. DeCaro, Jeremy C. Durack, Allen D. Everett, John B. Gordon, William E. Hammond, Ziyad M. Hijazi, Vikram S. Kashyap, Merrill Knudtson, Michael J. Landzberg, Marco A. Martinez-Rios, Lisa A. Riggs, Kui Hian Sim, David J. Slotwiner, Harry Solomon, Wilson Y. Szeto, Bonnie H. Weiner, William S. Weintraub, John R. Windle
Journal: Circulation (2014)
Abstract 13783: Paradigms to Predict Cardiometabolic Disease in African Descent Populations Should Focus on HDL-Cholesterol Rather than Triglyceride
Authors: Anne E Sumner, Caroline K Thoreson, Madia Ricks, Stephanie T Chung
Journal: Circulation (2014)

Paradigms for the early detection of cardiometabolic disease usually incorporate both elevated triglyceride (TG) and low high density lipoprotein -cholesterol (HDL-C). However, African-Americans with cardiometabolic disease usually have normal TG levels. The HDL-C pattern of African-Americans with cardiometabolic disease is uncertain. The TG and HDL-C pattern in Africans with cardiometabolic disease is unknown. To clarify the TG and HDL-C pattern in African descent populations with cardiometabolic disease, 377 blacks (167 African-Americans, 210 African immigrants, 59% male, age 36±9y, mean±SD, range 20-64y, BMI 29.0±6.3 kg/m2, range 18.5-54.7) had glucose tolerance status determined by OGTT, lipid profiles and insulin resistance determined by the insulin sensitivity index (SI). Insulin resistance was defined as the lowest quartile of SI (&lt;2.18 L/mU - 1min- 1). Metabolic triad was defined as hyperinsulinemia (fasting insulin≥3.7 μU/mL), hyperapolipoproteinB (≥64 mg/dL) and sdLDL(≥21.5 nm) based on the median values of the group with normal BMI. Cardiometabolic disease was defined as one or more of the following: pre-diabetes, diabetes, insulin resistance or metabolic triad. The frequency with which hypertriglyceridemia (TG≥150 mg/dL) or low HDL-C (&lt;40 mg/dL in men or &lt;50 mg/dL in women) occurred in the presence of cardiometabolic disease was determined. The prevalence of cardiometabolic disease did not differ in African-Americans and African immigrants (63% vs. 60%, P=0.51). TG and HDL-C levels in blacks with cardiometabolic disease did not differ by African ancestry. In the presence of cardiometabolic disease, TG levels were 80±40 vs. 87±43, P=0.24, resp. while HDL-C levels in men were: 45±11 vs. 44±12, P=0.63, and in women: 48±10 vs. 49±10, P=0.86). Less than 10% of people with cardiometabolic disease had TG≥150 mg/dL. However, 42% of people with cardiometabolic disease had low HDL-C. If HDL-C levels were low, the odds of having cardiometabolic disease was 2.84 (95% CI 1.76, 4.59. P&lt;0.001). Overall, more than 40% of people with cardiometabolic disease had low HDL while &lt;10% had elevated TG levels. Therefore, paradigms to detect cardiometabolic disease in African descent populations should focus on HDL-C rather than TG.
Anti-HDGF Targets Cancer and Cancer Stromal Stem Cells Resistant to Chemotherapy
Authors: Jun Zhao, Mark Z. Ma, Hening Ren, Zhenqiu Liu, Martin J. Edelman, Hong Pan, Li Mao
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Approximately one third of the patients with advanced non–small cell lung carcinoma (NSCLC) will initially respond to platinum-based chemotherapy, but virtually all tumors will progress (acquired resistance). The remainder will progress during initial treatment (primary resistance). In this study, we test whether the treatment can be improved by inhibiting hepatoma-derived growth factor (HDGF). Experimental Design: Thirteen primary NSCLC heterotransplant models were used to test four treatment regimens, including platinum-based chemotherapy with and without bevacizumab (VEGF-neutralizing antibody) or HDGF-H3 (HDGF-neutralizing antibody) and chemotherapy with bevacizumab and HDGF-H3. Expression of stem cell–related genes was measured using quantitative reverse transcription PCR (qRT-PCR) and immunohistochemistry. Results: Among 13 primary NSCLC heterotransplant models, three (23%) responded to chemotherapy but all relapsed within 20 days. The residual tumors after response to the chemotherapy exhibited an increased expression in 51 (61%) of 84 genes related with stem cell proliferation and maintenance, particularly those in Notch and Wnt pathways, suggesting enrichment for stem cell populations in the residual tumors. Interestingly, tumors from two of three models treated with HDGF-H3, bevacizumab, and chemotherapy combination did not relapse during 6 months of posttreatment observation. Importantly, this treatment combination substantially downregulated expression levels in 57 (68%) of 84 stem cell–related genes, including 34 (67%) of 51 genes upregulated after the chemotherapy. Conclusion: These data support the hypothesis that cancer stem cells (CSC) are a mechanism for chemotherapy resistance and suggest HDGF may be a target for repressing CSCs to prevent relapse of NSCLC sensitive to chemotherapy. Clin Cancer Res; 19(13); 3567–76. ©2013 AACR.
Abstract 2598: Dietary compounds EGCG and sulforaphane differentially reactivate ER-α in African American and Caucasian breast cancer cells.
Authors: Tabitha M. Hardy, Olayode O. Babatunde, Trygve O. Tollofsbol
Journal: Cancer Research (2013)

Abstract Breast cancer will affect 1 out of 8 women in their lifetimes and is one of the leading causes of cancer death among women of all races. African American (AA) women, in particular, have a higher breast cancer mortality rate than women of other ethnicities, revealing a clear ethnic disparity. Additionally, AA women tend to have larger, more aggressive tumors and are more likely to be diagnosed with estrogen receptor-α (ER-α)- negative and triple negative breast cancers. While sSocio-economic, cultural and environmental factors are thought to contribute to these disparitiess; however, the extent these aspects play in influencing tumor growth and development is not clearly defined. We sought to address the important question pertaining to the relative contribution of diet in breast cancer disparities and epigenetic modifications. We determined theTo do so we observed the effects of bioactive dietary compounds, (−)-epigallocatechin-3-gallate (EGCG), found in green tea, and sulforaphane (SFN), found cruciferous vegetables such as broccoli sprouts and cauliflower, on breast cancer cells. In order to determine whether ethnicity played a role in these effects breast cancer cells derived from AA and Caucasian (CAU) women that were treated separately or in combination with EGCG and/or SFN. Cell lines were evaluated for cell viability, cellular responses and expression of several genes including ER-α and those associated with epigenetic modifications. We found that AA breast cancer cells displayed distinct variations in response to ECGG and SFN treatments when compared to CAU cell lines. In particular,Specifically, AA-derived cell lines had a delayed ER-α reactivation at a higher dose than did CAU cells. Further, differential expression of several epigenetic modifiers and cancer-related genes was observed in AA cells. These results support the hypothesis that differences variations in gene expression in AA women with breast cancer may be influenced by diet and that innate biological variances based on ethnicity may contribute to these dissimilarities. Citation Format: Tabitha M. Hardy, Olayode O. Babatunde, Trygve O. Tollofsbol. Dietary compounds EGCG and sulforaphane differentially reactivate ER-α in African American and Caucasian breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2598. doi:10.1158/1538-7445.AM2013-2598
Quality indicators in ovarian cancer surgery: Report from the French Society of Gynecologic Oncology (Société Française d'Oncologie Gynécologique, SFOG)
Authors: D. Querleu, I. Ray-Coquard, J.M. Classe, J.S. Aucouturier, F. Bonnet, P. Bonnier, E. Darai, M. Devouassoux, L. Gladieff, O. Glehen, C. Haie-Meder, F. Joly, F. Lécuru, J.P. Lefranc, C. Lhommé, P. Morice, A. Salengro, E. Stoeckle, S. Taieb, Z.X. Zeng, E. Leblanc
Journal: Annals of Oncology (2013)