tbuckley/cabot-search huggingface dataset:
Patterns of Gene Expression and Copy-Number Alterations in von-Hippel Lindau Disease-Associated and Sporadic Clear Cell Carcinoma of the Kidney
Authors: Rameen Beroukhim, Jean-Philippe Brunet, Arianna Di Napoli, Kirsten D. Mertz, Apryle Seeley, Maira M. Pires, David Linhart, Robert A. Worrell, Holger Moch, Mark A. Rubin, William R. Sellers, Matthew Meyerson, W. Marston Linehan, William G. Kaelin, Sabina Signoretti
Journal: Cancer Research (2009)

Abstract Recent insights into the role of the von-Hippel Lindau (VHL) tumor suppressor gene in hereditary and sporadic clear-cell renal cell carcinoma (ccRCC) have led to new treatments for patients with metastatic ccRCC, although virtually all patients eventually succumb to the disease. We performed an integrated, genome-wide analysis of copy-number changes and gene expression profiles in 90 tumors, including both sporadic and VHL disease-associated tumors, in hopes of identifying new therapeutic targets in ccRCC. We identified 14 regions of nonrandom copy-number change, including 7 regions of amplification (1q, 2q, 5q, 7q, 8q, 12p, and 20q) and 7 regions of deletion (1p, 3p, 4q, 6q, 8p, 9p, and 14q). An analysis aimed at identifying the relevant genes revealed VHL as one of three genes in the 3p deletion peak, CDKN2A and CDKN2B as the only genes in the 9p deletion peak, and MYC as the only gene in the 8q amplification peak. An integrated analysis to identify genes in amplification peaks that are consistently overexpressed among amplified samples confirmed MYC as a potential target of 8q amplification and identified candidate oncogenes in the other regions. A comparison of genomic profiles revealed that VHL disease-associated tumors are similar to a subgroup of sporadic tumors and thus more homogeneous overall. Sporadic tumors without evidence of biallelic VHL inactivation fell into two groups: one group with genomic profiles highly dissimilar to the majority of ccRCC and a second group with genomic profiles that are much more similar to tumors with biallelic inactivation of VHL. [Cancer Res 2009;69(11):4674–81]
Myocardial Injury and Ventricular Dysfunction Related to Training Levels Among Nonelite Participants in the Boston Marathon
Authors: Tomas G. Neilan, James L. Januzzi, Elizabeth Lee-Lewandrowski, Thanh-Thao Ton-Nu, Danita M. Yoerger, Davinder S. Jassal, Kent B. Lewandrowski, Arthur J. Siegel, Jane E. Marshall, Pamela S. Douglas, David Lawlor, Michael H. Picard, Malissa J. Wood
Journal: Circulation (2006)

Background— Multiple studies have individually documented cardiac dysfunction and biochemical evidence of cardiac injury after endurance sports; however, convincing associations between the two are lacking. We aimed to determine the associations between the observed transient cardiac dysfunction and biochemical evidence of cardiac injury in amateur participants in endurance sports and to elicit the risk factors for the observed injury and dysfunction. Methods and Results— We screened 60 nonelite participants, before and after the 2004 and 2005 Boston Marathons, with echocardiography and serum biomarkers. Echocardiography included conventional measures as well as tissue Doppler–derived strain and strain rate imaging. Biomarkers included cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP). All subjects completed the race. Echocardiographic abnormalities after the race included altered diastolic filling, increased pulmonary pressures and right ventricular dimensions, and decreased right ventricular systolic function. At baseline, all had unmeasurable troponin. After the race, &gt;60% of participants had increased cTnT &gt;99th percentile of normal (&gt;0.01 ng/mL), whereas 40% had a cTnT level at or above the decision limit for acute myocardial necrosis (≥0.03 ng/mL). After the race, NT-proBNP concentrations increased from 63 (interquartile range [IQR] 21 to 81) pg/mL to 131 (IQR 82 to 193) pg/mL ( P &lt;0.001). The increase in biomarkers correlated with post-race diastolic dysfunction, increased pulmonary pressures, and right ventricular dysfunction (right ventricular mid strain, r =−0.70, P &lt;0.001) and inversely with training mileage ( r =−0.71, P &lt;0.001). Compared with athletes training &gt;45 miles/wk, athletes who trained ≤35 miles/wk demonstrated increased pulmonary pressures, right ventricular dysfunction (mid strain 16±5% versus 25±4%, P &lt;0.001), myocyte injury (cTnT 0.09 versus &lt;0.01 ng/mL, P &lt;0.001), and stress (NT-proBNP 182 versus 106 pg/mL, P &lt;0.001). Conclusions— Completion of a marathon is associated with correlative biochemical and echocardiographic evidence of cardiac dysfunction and injury, and this risk is increased in those participants with less training.
Intra- and extracellular K+ and Na+ activities and resting membrane potential in sheep cardiac purkinje strands.
Authors: S S Sheu, M Korth, D A Lathrop, H A Fozzard
Journal: Circulation Research (1980)

K+- and Na+-selective liquid ion-exchanger microelectrodes were used to measure intracellular K+ activity (aK i) and intracellular Na+ activity (aNa i) of sheep cardiac Purkinje strands in different solutions. In Tyrode's solution with an extracellular K+ concentration ([K+]o) of 5.4 mM, aK i was between 80 and 140 mM and averaged 109.6 +/- 4.0 mM (mean +/- SE, 20 strands). The measured aK i was closely correlated with the resting membrane potential, so that the K+ equilibrium potential was always about 10 mV more negative. When [K+]o was lower than 5.4 mM, aK i fell, and when [K+]o was higher than 5.4 mM it increased, aNa i was between 4 and 12 mM, and averaged 6.6 +/- 0.6 mM (14 strands). Its variation was also correlated with resting potential. Over a wide range of [K+]o and extracellular Na+ concentrations ([Na+]o), the aiNa changes were such that Na+ equilibrium potential remained between +70 and +80 mV. The quiescent membrane behaved as a K+-electrode when [K+]o was higher than 5.4 mM. When [K+]o was low and [Na+]o was zero, then Ca2+ and perhaps Cl- contributed to the resting potential.
Randomized Phase III Trial of Temsirolimus Versus Sorafenib As Second-Line Therapy After Sunitinib in Patients With Metastatic Renal Cell Carcinoma
Authors: Thomas E. Hutson, Bernard Escudier, Emilio Esteban, Georg A. Bjarnason, Ho Yeong Lim, Kenneth B. Pittman, Peggy Senico, Andreas Niethammer, Dongrui Ray Lu, Subramanian Hariharan, Robert J. Motzer
Journal: Journal of Clinical Oncology (2013)

This international phase III trial (Investigating Torisel As Second-Line Therapy [INTORSECT]) compared the efficacy of temsirolimus (mammalian target of rapamycin inhibitor) and sorafenib (vascular endothelial growth factor receptor [VEGFR] tyrosine kinase inhibitor) as second-line therapy in patients with metastatic renal cell carcinoma (mRCC) after disease progression on sunitinib.In total, 512 patients were randomly assigned 1:1 to receive intravenous temsirolimus 25 mg once weekly (n = 259) or oral sorafenib 400 mg twice per day (n = 253), with stratification according to duration of prior sunitinib therapy (≤ or > 180 days), prognostic risk, histology (clear cell or non-clear cell), and nephrectomy status. The primary end point was progression-free survival (PFS) by independent review committee assessment. Safety, objective response rate (ORR), and overall survival (OS) were secondary end points.Primary analysis revealed no significant difference between treatment arms for PFS (stratified hazard ratio [HR], 0.87; 95% CI, 0.71 to 1.07; two-sided P = .19) or ORR. Median PFS in the temsirolimus and sorafenib arms were 4.3 and 3.9 months, respectively. There was a significant OS difference in favor of sorafenib (stratified HR, 1.31; 95% CI, 1.05 to 1.63; two-sided P = .01). Median OS in the temsirolimus and sorafenib arms was 12.3 and 16.6 months, respectively. Safety profiles of both agents were consistent with previous studies.In patients with mRCC and progression on sunitinib, second-line temsirolimus did not demonstrate a PFS advantage compared with sorafenib. The longer OS observed with sorafenib suggests sequenced VEGFR inhibition may benefit patients with mRCC.
Chronic pancreatitis: diagnosis and management of complications
Authors: N I Church, S P Pereira, D Churchill, S Cairns, A R W Hatfield, G J M Webster
Journal: Gut (2007)

This is an introduction to the Gut tutorial “Chronic pancreatitis: diagnosis and management of complications” hosted on BMJ Learning—the best available learning website for medical professionals, from the BMJ Group.

Chronic pancreatitis is a progressive inflammatory condition that leads to irreversible loss of pancreatic structure and function. Eighty percent of cases are due to alcohol misuse. Chronic pancreatitis usually presents with abdominal pain, followed at a variable interval …
Thermogenic effect of bronchodilators in patients with chronic obstructive pulmonary disease
Authors: L. Burdet, B. de Muralt, Y. Schutz, J. W. Fitting
Journal: Thorax (1997)

Patients with chronic obstructive pulmonary disease (COPD) are frequently malnourished and have increased resting energy expenditure (REE). An increase in the work of breathing is generally considered to be the main cause of this hypermetabolism, but other factors may also be implicated. Bronchodilators may decrease the work of breathing by reducing airway obstruction, but beta 2 adrenergic agents have a thermogenic effect. The aim of this study was to determine the effect of salbutamol and ipratropium bromide administration on REE in patients with COPD.Thirteen patients (10 men) of mean (SD) age 68.3 (7.3) years and forced expiratory volume in one second (FEV1) 39.0 (17.0)% predicted were studied on three consecutive days. The REE was measured by indirect calorimetry at 30, 60, 120, and 180 minutes after double blind nebulisation of either salbutamol, ipratropium bromide, or placebo in random order.FEV1 increased both after salbutamol and after ipratropium. The difference in the mean response between salbutamol and placebo over 180 minutes was +199 ml (95% CI +104 to +295). The difference in mean response between ipratropium and placebo was +78 ml (95% CI +2 to +160). REE increased after salbutamol but was not changed after ipratropium. The difference in mean response between salbutamol and placebo was +4.8% of baseline REE (95% CI +2.2 to +7.4). Heart rate increased after salbutamol but not after ipratropium. The difference in the mean response between salbutamol and placebo was +5.5 beats/ min (95% CI +2.6 to +8.4).Salbutamol, but not ipratropium bromide, induces a sustained increase in the REE of patients with COPD despite a reduction in airway obstruction.
Predicting Postconcussion Syndrome After Mild Traumatic Brain Injury in Children and Adolescents Who Present to the Emergency Department
Authors: Lynn Babcock, Terri Byczkowski, Shari L. Wade, Mona Ho, Sohug Mookerjee, Jeffrey J. Bazarian
Journal: JAMA Pediatrics (2012)

To determine the acute predictors associated with the development of postconcussion syndrome (PCS) in children and adolescents after mild traumatic brain injury.Retrospective analysis of a prospective observational study.Pediatric emergency department (ED) in a children's hospital.Four hundred six children and adolescents aged 5 to 18 years.Closed head trauma.The Rivermead Post Concussion Symptoms Questionnaire administered 3 months after the injury.Of the patients presenting to the ED with mild traumatic brain injury, 29.3% developed PCS. The most frequent PCS symptom was headache. Predictors of PCS, while controlling for other factors, were being of adolescent age, headache on presentation to the ED, and admission to the hospital. Patients who developed PCS missed a mean (SD) of 7.4 (13.9) days of school.Adolescents who have headache on ED presentation and require hospital admission at the ED encounter are at elevated risk for PCS after mild traumatic brain injury. Interventions to identify this population and begin early treatment may improve outcomes and reduce the burden of disease.
Advances in Treatment of Bipolar Disorder: Review of Psychiatry, Volume 24edited by Terrence A. Ketter, M.D. Series editors: John M. Oldham, M.D., M.S., and Michelle B. Riba, M.D., M.S. Arlington, Va., American Psychiatric Publishing, 2005, 280 pp., $36.95.
Authors: DANIEL P. VAN KAMMEN
Journal: American Journal of Psychiatry (2007)
Intravascular Complications of Central Venous Catheterization by Insertion Site
Authors: Jean-Jacques Parienti, Nicolas Mongardon, Bruno Mégarbane, Jean-Paul Mira, Pierre Kalfon, Antoine Gros, Sophie Marqué, Marie Thuong, Véronique Pottier, Michel Ramakers, Benoît Savary, Amélie Seguin, Xavier Valette, Nicolas Terzi, Bertrand Sauneuf, Vincent Cattoir, Leonard A. Mermel, Damien du Cheyron
Journal: New England Journal of Medicine (2015)

Three anatomical sites are commonly used to insert central venous catheters, but insertion at each site has the potential for major complications.
Prevalence of Human Papillomavirus in Cervical Cancer: a Worldwide Perspective
Authors: F. X. Bosch, M. M. Manos, N. Munoz, M. Sherman, A. M. Jansen, J. Peto, M. H. Schiffman, V. Moreno, R. Kurman, K. V. Shan
Journal: JNCI Journal of the National Cancer Institute (1995)

Epidemiologic studies have shown that the association of genital human papillomavirus (HPV) with cervical cancer is strong, independent of other risk factors, and consistent in several countries. There are more than 20 different cancer-associated HPV types, but little is known about their geographic variation.Our aim was to determine whether the association between HPV infection and cervical cancer is consistent worldwide and to investigate geographic variation in the distribution of HPV types.More than 1000 specimens from sequential patients with invasive cervical cancer were collected and stored frozen at 32 hospitals in 22 countries. Slides from all patients were submitted for central histologic review to confirm the diagnosis and to assess histologic characteristics. We used polymerase chain reaction-based assays capable of detecting more than 25 different HPV types. A generalized linear Poisson model was fitted to the data on viral type and geographic region to assess geographic heterogeneity.HPV DNA was detected in 93% of the tumors, with no significant variation in HPV positivity among countries. HPV 16 was present in 50% of the specimens, HPV 18 in 14%, HPV 45 in 8%, and HPV 31 in 5%. HPV 16 was the predominant type in all countries except Indonesia, where HPV 18 was more common. There was significant geographic variation in the prevalence of some less common virus types. A clustering of HPV 45 was apparent in western Africa, while HPV 39 and HPV 59 were almost entirely confined to Central and South America. In squamous cell tumors, HPV 16 predominated (51% of such specimens), but HPV 18 predominated in adenocarcinomas (56% of such tumors) and adenosquamous tumors (39% of such tumors).Our results confirm the role of genital HPVs, which are transmitted sexually, as the central etiologic factor in cervical cancer worldwide. They also suggest that most genital HPVs are associated with cancer, at least occasionally.The demonstration that more than 20 different genital HPV types are associated with cervical cancer has important implications for cervical cancer-prevention strategies that include the development of vaccines targeted to genital HPVs.
Prediagnostic non-steroidal anti-inflammatory drug use and survival after diagnosis of colorectal cancer
Authors: A. E. Coghill, P. A. Newcomb, P. T. Campbell, A. N. Burnett-Hartman, S. V. Adams, E. M. Poole, J. D. Potter, C. M. Ulrich
Journal: Gut (2010)

<h3>Objective</h3> Non-steroidal anti-inflammatory drug (NSAID) use decreases both the incidence of colorectal cancer and recurrence of adenomas among patients with prior colorectal neoplasia. However, few studies have investigated the association between NSAID use and colorectal cancer-specific survival. The role of prediagnostic NSAID use was therefore examined in relation to colorectal cancer-specific survival among cases from the Seattle Colon Cancer Family Registry (Seattle Colon CFR). <h3>Methods</h3> This was a follow-up study that included incident cases of colorectal cancer from the Seattle Colon CFR. Cases were aged 20–74, diagnosed from 1997 to 2002, and were identified using the population-based Puget Sound SEER registry. Detailed information on history of NSAID use, including type, recency and duration, was collected through an interviewer-administered questionnaire. Follow-up for mortality was completed through linkages to the National Death Index. The main outcome measure was death due to colorectal cancer after diagnosis. Cox proportional hazards regression was used to investigate the relationship between prediagnostic NSAID use and colorectal cancer-specific mortality among cases. <h3>Results</h3> NSAID use prior to colorectal cancer diagnosis was associated with an ∼20% lower rate of colorectal cancer mortality after diagnosis compared with never use (HR 0.79; 95% CI 0.65 to 0.97). This relationship appeared to be duration dependent, with longer reported use prior to diagnosis associated with lower rates of colorectal cancer mortality among cases. The most pronounced reductions in mortality were observed among cases diagnosed with proximal disease (HR 0.55; 95% CI 0.37 to 0.82), whereas no association was observed between NSAID use prior to diagnosis and colorectal cancer-specific mortality among cases diagnosed with distal or rectal disease. <h3>Conclusions</h3> The findings suggest that regular use of NSAIDs prior to diagnosis is associated with improved colorectal cancer survival, particularly among cases diagnosed with proximal disease and in longer term NSAID users.
A transformation-associated 130-kD cell surface glycoprotein is growth controlled in normal human cells.
Authors: C E Klein, H L Ozer, F Traganos, J Atzpodien, H F Oettgen, L J Old
Journal: The Journal of Experimental Medicine (1988)

Two characteristics of cell surface molecules involved in the regulation of cell proliferation are altered expression in relation to growth phase in normal cells and overexpression in transformed cells. Here, we describe a similar pattern of expression for a 130-kD cell surface glycoprotein (gp 130) in human cells. Synthesis and cell surface expression of gp130 were greatly increased in both virally and chemically transformed fibroblasts, fibrosarcomas, a squamous cell carcinoma of the skin, and T cell leukemia lines. Furthermore, gp130 expression was induced in serum-starved fetal fibroblasts by serum stimulation, and in fresh T cells by various activating agents. Expression in response to serum stimulation was associated primarily with the transition from a quiescent state (G0) into the cell cycle (G1).
Study of Failure Pattern Among High-Risk Breast Cancer Patients With or Without Postmastectomy Radiotherapy in Addition to Adjuvant Systemic Therapy: Long-Term Results From the Danish Breast Cancer Cooperative Group DBCG 82 b and c Randomized Studies
Authors: Hanne M. Nielsen, Marie Overgaard, Cai Grau, Anni R. Jensen, Jens Overgaard
Journal: Journal of Clinical Oncology (2006)

Postmastectomy radiotherapy (RT) in high-risk breast cancer patients can reduce locoregional recurrences (LRRs) and improve disease-free and overall survival. The aim of this analysis was to examine the overall disease recurrence pattern among patients randomly assigned to receive treatment with or without RT.A long-term follow-up was performed among the 3,083 patients from the Danish Breast Cancer Cooperative Group 82 b and c trials, except in those already recorded with distant metastases (DM) or contralateral breast cancer (CBC). The end points were LRR, DM, and CBC, and the follow-up continued until DM, CBC, emigration, or death. Information was selected from medical records, general practitioners, and the National Causes of Death Registry. The median potential follow-up time was 18 years.The 18-year probability of any first breast cancer event was 73% and 59% (P < .001) after no RT and RT, respectively (relative risk [RR], 0.68; 95% CI, 0.63 to 0.75). The 18-year probability of LRR (with or without DM) was 49% and 14% (P < .001) after no RT and RT, respectively (RR, 0.23; 95% CI, 0.19 to 0.27). The 18-year probability of DM subsequent to LRR was 35% and 6% (P < .001) after no RT and RT, respectively (RR, 0.15; 95% CI, 0.11 to 0.20), whereas the probability of any DM was 64% and 53% (P < .001) after no RT versus RT, respectively (RR, 0.78; 95% CI, 0.71 to 0.86).Postmastectomy RT changes the disease recurrence pattern in high-risk breast cancer patients; fewer patients have LRR as first site of recurrence, and overall fewer patients have DM.
A Double-Blind, Placebo-Controlled, Randomized Trial of Oral Sodium Clodronate for Metastatic Prostate Cancer (MRC PR05 Trial)
Authors: D. P. Dearnaley
Journal: JNCI Journal of the National Cancer Institute (2003)

The most frequent site of metastases from prostate cancer is bone. Bisphosphonates reduce excessive bone turnover while preserving bone structure and mineralization in patients with other tumor types. We conducted a double-blind, placebo-controlled, randomized trial to determine whether the first-generation bisphosphonate sodium clodronate could improve bone progression-free survival (BPFS) times among men with bone metastases from prostate cancer.Between June 1994 and July 1998, 311 men who were starting or responding to first-line hormone therapy for bone metastases were randomly assigned to receive oral sodium clodronate (2080 mg/day) or placebo for a maximum of 3 years. The primary endpoint of the trial was symptomatic BPFS. Secondary endpoints included overall survival, treatment toxicity, and change in World Health Organization (WHO) performance status. Time-to-event data were analyzed using the log-rank chi-square test and Kaplan-Meier curves. All statistical tests were two-sided.Baseline characteristics were balanced across the two groups. After a median follow-up of 59 months, the sodium clodronate group showed statistically nonsignificant better symptomatic BPFS (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.61 to 1.02; P =.066) and overall survival (HR = 0.80, 95% CI = 0.62 to 1.03; P =.082) than the control group. Patients in the clodronate group were less likely to have a worsened WHO performance status (HR = 0.71, 95% CI = 0.56 to 0.92; P =.008). However, the clodronate group reported more gastrointestinal problems and increased lactate dehydrogenase levels and required more frequent modification of the trial drug dose (HR for any adverse event = 1.71, 95% CI = 1.21 to 2.41; P =.002). Results of subgroup analyses suggested that clodronate might be more effective the sooner after diagnosis of metastatic bone disease it is started.These results suggest that further studies of the effect of newer generation bisphosphonates on BPFS in men with metastatic prostate cancer are warranted.