tbuckley/cabot-search huggingface dataset:
Schedule Dependence for Cisplatin and Etoposide Multifraction Treatments of Spheroids
Authors: R. E. Durand, S. L. Vanderbyl
Journal: JNCI Journal of the National Cancer Institute (1990)

Cisplatin and etoposide are both widely used as antineoplastic chemotherapeutic agents. Two approaches are generally adopted when an attempt is made to maximize the efficiency of these drugs: concurrent use (where synergism is expected) or sequential administrations (exploiting the antiproliferative effects of etoposide). To differentiate between these approaches in aquantitative manner, we exposed an in vitro tumor model (V79 multicell spheroids) to the drugs, using treatment regimens with a constant weekly dose intensity. Some treatment schedules suggested the development of drug resistance, but this resulted from a changing growth fraction in the spheroids rather than from selection for or induction of cellular resistance. Fewer administrations of larger doses were generally less satisfactory than multiple, smaller treatments. The most effective sequence was an alternating regimen, by which the cytoreductive effects of cisplatin resulted in recruitment of quiescent cells into active proliferation, enhancing in turn the efficiency of subsequent etoposide treatment. [J Natl Cancer Inst 82:1841–1845, 1990]
Bile acids modulate glucocorticoid metabolism and the hypothalamic–pituitary–adrenal axis in obstructive jaundice
Authors: Alison D. McNeilly, David P. Macfarlane, Emmett O’Flaherty, Dawn E. Livingstone, Tijana Mitić, Kirsty M. McConnell, Scott M. McKenzie, Eleanor Davies, Rebecca M. Reynolds, Helle C. Thiesson, Ole Skøtt, Brian R. Walker, Ruth Andrew
Journal: Journal of Hepatology (2010)

Suppression of the hypothalamic-pituitary-adrenal axis occurs in cirrhosis and cholestasis and is associated with increased concentrations of bile acids. We investigated whether this was mediated through bile acids acting to impair steroid clearance by inhibiting glucocorticoid metabolism by 5beta-reductase.
Prostate Cancer, Version 3.2012 Featured Updates to the NCCN Guidelines
Authors: James L. Mohler, Andrew J. Armstrong, Robert R. Bahnson, Barry Boston, J. Erik Busby, Anthony Victor D’Amico, James A. Eastham, Charles A. Enke, Thomas Farrington, Celestia S. Higano, Eric Mark Horwitz, Philip W. Kantoff, Mark H. Kawachi, Michael Kuettel, Richard J. Lee, Gary R. MacVicar, Arnold W. Malcolm, David Miller, Elizabeth R. Plimack, Julio M. Pow-Sang, Mack Roach, Eric Rohren, Stan Rosenfeld, Sandy Srinivas, Seth A. Strope, Jonathan Tward, Przemyslaw Twardowski, Patrick C. Walsh, Maria Ho, Dorothy A. Shead
Journal: Journal of the National Comprehensive Cancer Network (2012)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer provide multidisciplinary recommendations for the clinical management of patients with prostate cancer. These NCCN Guidelines Insights highlight notable recent updates. Abiraterone acetate is a first-in-class hormonal agent that represents a new standard of care for patients with metastatic castration-recurrent prostate cancer who have previously received docetaxel (category 1 recommendation). Abiraterone acetate also received category 2B recommendations in the prechemotherapy setting for asymptomatic patients or symptomatic patients who are not candidates for docetaxel. The NCCN Prostate Cancer Panel also added new indications for existing agents, including the option of sipuleucel-T as second-line therapy. In addition, brachytherapy in combination with external beam radiation therapy with or without androgen deprivation therapy is now an alternative for patients with high-risk localized tumors or locally advanced disease.
Development Of Chronic Kidney Disease and Cardiovascular Prognosis in Essential Hypertensive Patients
Authors: Julia[Combining Acute Accent]n Segura, Carlos Campo, Paloma Gil, Cecilia Rolda[Combining Acute Accent]n, Luis Vigil, Jose[Combining Acute Accent] L. Rodicio, Luis M. Ruilope
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. The existence of a significant percentage of treated hypertensive patients presenting a diminished renal function has been recently described. Mild renal function abnormalities are recognized as powerful predictors of cardiovascular morbidity and mortality. However, longitudinal data demonstrating this association are lacking. The objectives of this study have been analysis of the evolution of GFR, assessed as creatinine clearance (CrCl), during long-term follow-up of hypertensive patients and evaluation of the impact of the development of chronic kidney disease (CKD) on cardiovascular prognosis. A historical cohort of 281 patients attending our Hypertension Unit was selected according to the following criteria: essential hypertension, more than 5 yr of follow-up, and normal GFR at baseline (CrCl &gt; 90 ml/min per 1.73 m<sup>2</sup>). Patients had an average follow-up of 13.2 ± 4.8 yr. Forty-one patients (14.6%) developed CKD (CrCl &lt; 60 ml/min per 1.73 m<sup>2</sup>) attributed to hypertensive nephrosclerosis. Initial serum creatinine, age, systolic BP at baseline, and average total cholesterol during follow-up were independent predictors of CKD development. Forty-nine (17.4%) of 281 patients presented a cardiovascular event during follow-up: 17 patients (40.6%) who developed CKD and 32 patients (13.3%) with preserved renal function (log rank test <i>P</i> &lt; 0.001). After adjustment in a Cox multivariate analysis, age, development of CKD during follow-up, and male gender were independent predictors of the appearance of cardiovascular events. In essential hypertensive patients with normal renal function at baseline, the development of CKD during the follow-up is strongly and independently related with poor cardiovascular prognosis.
Validation of respiratory inductive plethysmography in people with obesity hypoventilation syndrome
Authors: Carly Hollier, Alison Harmer, Lyndal Maxwell, Collette Menadue, Amanda Piper, Grant Willson
Journal: European Respiratory Journal (2012)

The excessive chest and abdominal adiposity present in obesity hypoventilation syndrome (OHS) may reduce the accuracy of respiratory inductive plethysmography (RIP). The aim of the study was to validate RIP measures of ventilation in OHS against a clinical standard (spirometry). Measures of tidal volume (V T ), minute ventilation (V E ) and respiratory rate (RR) were obtained simultaneously from RIP (LifeShirt™) and a spirometer during two 40-minute air/supplemental O 2  breathing tests. 16 paired samples were obtained per subject. Using the Bland Altman method, bias was expressed as spirometer–RIP mean difference (MD), and as a percentage. Error was expressed as limits of agreement (LOA) and as a percentage. Differences between groups were assessed with independent samples t-tests. 162 viable paired samples were obtained from 13 subjects with OHS and 197 paired samples were obtained from 13 age- and gender-matched controls. Error of RIP measures was larger in subjects with OHS: V T  MD=3mL (1%), LOA=-216 to 222mL (±36%) compared with controls, MD=5mL (1%), LOA=-160 to 169mL (±20%); V E : MD=0.2L/min (2%), LOA=-4.1 to 4.4L/min (±36%) in subjects with OHS compared with MD=0.1L/min (1%), LOA=-1.4 to 1.5L/min (±20%) for controls; and RR: MD=0.2br/min (2%), LOA=-5 to 5br/min (±27%) in subjects with OHS compared with MD=-0.1 br/min (1%), LOA=-1 to 1br/min (±12%) for controls. Between group differences were only statistically significant for RR (p T  %error correlated strongly with body mass index (r s =0.53, p s =0.61, p
Toxicity and therapeutic efficacy of high-dose interleukin 2. In vivo infusion of antibody to NK-1.1 attenuates toxicity without compromising efficacy against murine leukemia.
Authors: D J Peace, M A Cheever
Journal: The Journal of Experimental Medicine (1989)

In the current study we used the therapy of established murine leukemia to identify the lymphocyte subsets responsible for toxicity and for therapeutic efficacy of high-dose IL-2. Initial results confirmed that high-dose IL-2 induces marked proliferation of a variety of host cells, including NK cells, Lyt-2+ T cells, L3T4+ T cells, and B cells. Infusion of antibody to NK-1.1 depleted NK-1.1+ cells in vivo and greatly reduced the toxicity of IL-2, but did not decrease therapeutic efficacy. By marked contrast, depletion of host T cells, either Lyt-2+ or L3T4+, had no effect on toxicity but greatly reduced therapeutic efficacy. The requirement for host T cells for the curative effect of IL-2 gives credence to the possibility that substantial efficacy of high-dose IL-2 against established malignancy may require existent host antitumor immunity. Since the human tumors that have been shown to have the most substantial responses to IL-2 (i.e., malignant melanoma and renal cell carcinoma) are those long considered to be immunogenic in the autochthonous host, the current study predicts that for these, as well as other immunogenic human tumors, it should be possible to decrease the toxicity and thus increase the therapeutic index of IL-2 by selectively depleting NK cells in vivo.
Left Atrial Relaxation and Left Ventricular Systolic Function Determine Left Atrial Reservoir Function
Authors: Paolo Barbier, Steven B. Solomon, Nelson B. Schiller, Stanton A. Glantz
Journal: Circulation (1999)

Background —Determinants of left atrial (LA) reservoir function and its influence on left ventricular (LV) function have not been quantified. Methods and Results —In an open-pericardium, paced (70 and 90 bpm) pig model of LV regional ischemia (left anterior descending coronary constriction), with high-fidelity LV, LA, and RV pressure recordings, we obtained the LA area with 2D automated border detection echocardiography, LA pressure-area loops, and Doppler transmitral flow. We calculated LV τ, LA relaxation (a−x pressure difference divided by time, normalized by a pressure), and stiffness (slope between x and v pressure points of v loop). Determinants of total LA reservoir (maximum−minimum area, cm 2 ) were identified by multiple regression analysis. Different mean rates of LA area increase identified 2 consecutive (early rapid and late slow) reservoir phases. During ischemia, LV long-axis shortening (LAS, LV base systolic descent) and LA reservoir area change decreased (7.3±0.3 [SEM] versus 5.6±0.3 cm 2 , P &lt;0.001) and LA stiffness increased (1.6±0.3 versus 3.1±0.3 mm Hg/cm 2 , P =0.009). Early reservoir area change depended on LA mean ejection rate (LA area at ECG P wave minus minimum area divided by time; multiple regression coefficient=0.9; P &lt;0.001) and relaxation (coefficient=4.9 cm 2 ×ms/s; P &lt;0.001). Late reservoir area change depended on LAS (coefficient=8 cm/s; P &lt;0.001). Total reservoir filling depended on LA stiffness (coefficient=−0.31 cm 4 /mm Hg; P =0.001) and cardiac output (coefficient=0.001 cm 2 ×min/L; P =0.002). The strongest predictor of cardiac output was LA reservoir filling (coefficient=301 L/min×cm 2 ; P &lt;0.001). The v loop area was determined by cardiac output, LV ejection time, τ, and early transmitral flow. Conclusions —Two (early and late) reservoir phases are determined by LA contraction and relaxation and LV base descent. Acute LV regional ischemia increases LA stiffness and impairs LA reservoir function by reducing LV base descent.
Increased postischemic brain injury in mice deficient in uracil-DNA glycosylase
Authors: Matthias Endres, Detlev Biniszkiewicz, Robert W. Sobol, Christoph Harms, Michael Ahmadi, Andreas Lipski, Juri Katchanov, Philipp Mergenthaler, Ulrich Dirnagl, Samuel H. Wilson, Andreas Meisel, Rudolf Jaenisch
Journal: Journal of Clinical Investigation (2004)

Uracil-DNA glycosylase (UNG) is involved in base excision repair of aberrant uracil residues in nuclear and mitochondrial DNA. Ung knockout mice generated by gene targeting are viable, fertile, and phenotypically normal and have regular mutation rates. However, when exposed to a nitric oxide donor, Ung–/– fibroblasts show an increase in the uracil/cytosine ratio in the genome and augmented cell death. After combined oxygen-glucose deprivation, Ung–/– primary cortical neurons have increased vulnerability to cell death, which is associated with early mitochondrial dysfunction. In vivo, UNG expression and activity are low in brains of naive WT mice but increase significantly after reversible middle cerebral artery occlusion and reperfusion. Moreover, major increases in infarct size are observed in Ung–/– mice compared with littermate control mice. In conclusion, our results provide compelling evidence that UNG is of major importance for tissue repair after brain ischemia.
microRNA evaluation of unknown primary lesions in the head and neck
Authors: Emma V Barker, Nilva K Cervigne, Patricia P Reis, Rashmi S Goswami, Wei Xu, Ilan Weinreb, Jonathan C Irish, Suzanne Kamel-Reid
Journal: Molecular Cancer (2009)

Abstract Unknown primary malignancy in the head and neck is not an infrequent diagnosis for patients with metastatic cervical lymph nodes. Although linked with a relatively good prognosis following radiation treatment, widespread radiation is coupled with significant morbidity. Altered microRNA (miRNA) expression has been associated with both cancer progression and metastasis. We sought to determine whether miRNA expression analysis could be used as a diagnostic tool to discover the primary site of malignancy, within the head and neck. We used quantitative real-time PCR to identify miRNA expression profiles of squamous cell carcinoma of the tonsil, base of tongue and post-nasal space, as well as their corresponding metastatic lymph nodes, from 6 patients. Our results revealed that each cancer maintained its expression profile between the primary site and the nodal metastasis (r = 0.82, p &lt; 0.0001). In addition, each anatomical sub-site maintained a distinct miRNA profile between individual patients (r = 0.79, p &lt; 0.0001). Finally, between sub-sites, the miRNA profiles were distinct (p &lt; 0.0001). As proof of principle, our study provides an indication that miRNA expression analysis may be useful to compare the primary lesion and local metastatic disease. This may be clinically relevant to predict the primary site of origin of metastatic disease, when the primary site remains obscure.
An antibody against the colony-stimulating factor 1 receptor depletes the resident subset of monocytes and tissue- and tumor-associated macrophages but does not inhibit inflammation
Authors: Kelli P. A. MacDonald, James S. Palmer, Stephen Cronau, Elke Seppanen, Stuart Olver, Neil C. Raffelt, Rachel Kuns, Allison R. Pettit, Andrew Clouston, Brandon Wainwright, Dan Branstetter, Jeffrey Smith, Raymond J. Paxton, Douglas Pat Cerretti, Lynn Bonham, Geoffrey R. Hill, David A. Hume
Journal: Blood (2010)
The importance of EN ISO 15189 accreditation of allergen-specific IgE determination for reliable<i>in vitro</i>allergy diagnosis
Authors: C. Lambert, A. Sarrat, F. Bienvenu, S. Brabant, P. Nicaise-Roland, M.-A. Alyanakian, P.-A. Apoil, C. Capron, R. Couderc, B. Evrard, D. Jaby, C. Hémont, C. Lainé, M. Lelong, D. Mariotte, J. Martinet, G. Rénier, J. Sainte-Laudy, T. Tabary, E. Treiner, B. Uring-Lambert, C. Vigneron, M. Vivinus, F. Witthuhn, J. Vitte
Journal: Allergy (2014)

Background Allergen-specific serum immunoglobulin E detection and quantification have become an important step in allergy diagnosis and follow-up. In line with the current trend of laboratory test accreditation to international standards, we set out to design and assess an accreditation procedure for allergen-specific serum IgE. Methods Method validation according to the accreditation procedure under the EN ISO 15189 standard was carried out for allergen-specific immunoglobulin E determination using the fluoroimmunoenzymatic method ImmunoCAP® (ThermoFisher). Data were produced by 25 hospital laboratories in France. A total of 29 allergen specificities including mixes, extracts, and molecular allergens were assayed. Allergen-specific serum immunoglobulin E concentrations ranged from 0.1 to 100 kUA/l. Results Repeatability, reproducibility, and accuracy results fulfilled method validation criteria for automated laboratory tests and proved similar irrespective of the allergen specificity, allergen-specific serum immunoglobulin E concentration, or individual laboratory. Conclusion Allergen-specific serum immunoglobulin E determination with the fluoroimmunoenzymatic method ImmunoCAP® is a highly repeatable, reproducible, and accurate method which may be considered as a single analyte assay in view of the EN ISO 15189 accreditation procedure.
Prenatal Concentrations of Polychlorinated Biphenyls, DDE, and DDT and Overweight in Children: A Prospective Birth Cohort Study
Authors: Damaskini Valvi, Michelle A. Mendez, David Martinez, Joan O. Grimalt, Maties Torrent, Jordi Sunyer, Martine Vrijheid
Journal: Environmental Health Perspectives (2011)

Recent experimental evidence suggests that prenatal exposure to endocrine-disrupting chemicals (EDCs) may increase postnatal obesity risk and that these effects may be sex or diet dependent.We explored whether prenatal organochlorine compound (OC) concentrations [polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyltrichloroethane (DDT)] were associated with overweight at 6.5 years of age and whether child sex or fat intakes modified these associations.We studied 344 children from a Spanish birth cohort established in 1997-1998. Overweight at 6.5 years was defined as a body mass index (BMI) z-score ≥ 85th percentile of the World Health Organization reference. Cord blood OC concentrations were measured and treated as categorical variables (tertiles). Children's diet was assessed by food frequency questionnaire. Relative risks (RRs) were estimated using generalized linear models.After multivariable adjustment, we found an increased RR of overweight in the third tertile of PCB exposure [RR = 1.70; 95% confidence interval (CI): 1.09, 2.64] and the second tertile of DDE exposure (RR = 1.67; 95% CI: 1.10, 2.55), but no association with DDT exposure in the population overall. Associations between overweight and PCB and DDE concentrations were strongest in girls (p-interaction between 0.01 and 0.28); DDT was associated with overweight only in boys. For DDT we observed stronger associations in children with fat intakes at or above compared with below the median, but this interaction was not significant (p-interaction > 0.05).This study suggests that prenatal OC exposures may be associated with overweight in children and that sex and high-fat intake may influence susceptibility.
Do we always need computed tomography to detect and treat parapneumonic pleural effusion?
Authors: B.K. Moffett
Journal: European Respiratory Journal (2012)

From the author:

G.F. Sterrazza Papa and co-workers raise valid concerns regarding excessive radiation exposure from chest computed tomography (CCT), which is an area of growing interest for both the medical community and the general public. It is correctly pointed out that multiple scans may mean a significantly increased lifetime attributable risk of cancer when estimated from prior studies of atomic bomb survivors and workers in the nuclear industry [1]. However, it would be remiss to not point out …
Population-Based Incidence of Type 2 Diabetes in Northern Spain
Authors: Sergio Valdés, Patricia Botas, Elias Delgado, Francisco Álvarez, Francisco Diaz Cadórniga
Journal: Diabetes Care (2007)

The aim of this study was to define the incidence of type 2 diabetes in a low-risk Caucasian population in northern Spain and its association with various risk factors.The Asturias Study is a prospective, population-based survey of diabetes and cardiovascular risk factors. The baseline examination was carried out during 1998-1999 when 1,034 individuals, aged 30-75 years, were randomly selected to determine the prevalence of type 2 diabetes and pre-diabetes in the Principality of Asturias (northern Spain). In 2004-2005, these same subjects were invited for a follow-up examination; 700 participated. This study includes only those individuals who did not have diabetes at baseline. We used the World Health Organization 1999 criteria to classify glucose metabolism at both baseline and follow-up.The incidence of diabetes adjusted for the age and sex structure of Asturias was 10.8 cases/1,000 person-years (95% CI 8.1-14.8). The incidence rates were 5 cases/1,000 person-years in individuals with normoglycemia, 21 cases/1,000 person-years in individuals with isolated impaired glucose tolerance (IGT), 34.7 cases/1,000 person-years in individuals with isolated impaired fasting glucose (IFG), and 95.2 cases/1,000 person-years in individuals with combined IFG-IGT. Stepwise multiple logistic regression analysis showed that, together with fasting plasma glucose (FPG) and 2-h plasma glucose, which were the strongest predictors of diabetes, triglycerides and BMI were also independently associated with progression to diabetes.In this 6-year prospective population-based study, we found an incidence of type 2 diabetes of 10.8 cases/1,000 person-years. Both FPG and 2-h plasma glucose were strongly predictive of diabetes, and their effect was additive.
Is skin toxicity a predictive or prognostic factor in EGFR-inhibition as treatment of advanced NSCLC?
Authors: Stefan Rüdiger, Cornelia Kropf-Sanchen, Gerald Schmid-Bindert, Thomas Wibmer, Kathrin Stoiber, Ioanna Blanta, Wolfgang Rottbauer, Christian Schumann
Journal: European Respiratory Journal (2012)

Targeted therapy addressing the Epidermal Growth Factor Receptor (EGFR) is available for the treatment of advanced NSCLC in our clinic with the Tyrosine Kinase Inhibitors Gefitinib and Erlotinib as well as the Monoclonal Antibody Cetuximab within the Gemtax Trial. We analysed clinical markers especially skin toxicity to find predictive and prognostic factors in this therapeutic setting.  Between March 2003 and December 2008 we began TKI therapy in 81 patients and between August 2006 and April 2011 cetuximab therapy in 51 patients (induction chemotherapy and cetuximab maintenance after four cycles). Median age was 66 years and median treatment duration 3 month, patients with treatment less than six weeks were not considered. We found a median Time to Progression (TTP) of 3.5 month and Overall Survival (OS) from start of therapy of 7.5 month. In the subgroup of patients who developed no or mild skin toxicity TTP was 2.0 month, whereas patients who developed a skin toxicity above grade I had a TTP of 4.5 month (p = 0.0002, HR = 0.48). Difference in OS in these two subgroups was 6.0 and 14.9 month respectively (p = 0.025, HR = 0.64). Age, gender, histology and smoking status showed less strong correlations.  Patients who develop skin toxicity during EGFR inhibiting therapy show a prolonged TTP and OS. To what extend skin toxicity is rather a prognostic factor is yet unclear. Further prospective studies should differentiate the predictive and prognostic value of skin toxicity. There is also a need to identify biomarkers that correlate with the development of skin toxicity and thus could predict a favourable therapeutic course of these costly targeted agents.