tbuckley/cabot-search huggingface dataset:
Determination of circulating blood volume by continuously monitoring hematocrit during hemodialysis.
Authors: J K Leypoldt, A K Cheung, R R Steuer, D H Harris, J M Conis
Journal: Journal of the American Society of Nephrology (1995)

Dialysis-induced hypovolemia occurs because the rate of extracorporeal ultrafiltration exceeds the rate of refilling of the blood compartment. The purpose of this study was to evaluate a method for calculating circulating blood volume (BV) during hemodialysis (HD) from changes in hematocrit (Hct) shortly (2 to 10 min) before and after ultrafiltration (UF) was abruptly stopped. Hct was monitored continuously during 93 HD treatment sessions in 16 patients by an optical technique and at selected times by centrifugation of blood samples. Total plasma protein and albumin concentrations were also measured at selected times. Continuously monitored Hct correlated with Hct determined by centrifugation (R = 0.89, N = 579). Relative changes in BV determined by continuously monitored Hct were not different from those determined by total plasma protein concentration (P = 0.05; N = 273). Calculated BV at the start of dialysis (4.1 +/- 1.3 L) was not different (P = 0.18, N = 12) from that derived anthropometrically from the patient's dry weight (4.6 +/- 0.8 L), and calculated BV when UF was stopped was 3.2 +/- 0.5 L (46 +/- 7 ml/kg body wt). These latter estimates of BV are consistent with those determined previously by dilution techniques in HD patients. It was concluded that (1) relative changes in BV assessed by continuously monitored Hct were unbiased and (2) BV can be determined noninvasively during HD by continuously monitoring Hct and temporarily stopping UF.
Bcl9/Bcl9l Are Critical for Wnt-Mediated Regulation of Stem Cell Traits in Colon Epithelium and Adenocarcinomas
Authors: Jürgen Deka, Norbert Wiedemann, Pascale Anderle, Fabienne Murphy-Seiler, Jennyfer Bultinck, Sven Eyckerman, Jean-Christophe Stehle, Sylvie André, Nathalie Vilain, Olav Zilian, Sylvie Robine, Mauro Delorenzi, Konrad Basler, Michel Aguet
Journal: Cancer Research (2010)

Canonical Wnt signaling plays a critical role in stem cell maintenance in epithelial homeostasis and carcinogenesis. Here, we show that in the mouse this role is critically mediated by Bcl9/Bcl9l, the mammalian homologues of Legless, which in Drosophila is required for Armadillo/beta-catenin signaling. Conditional ablation of Bcl9/Bcl9l in the intestinal epithelium, where the essential role of Wnt signaling in epithelial homeostasis and stem cell maintenance is well documented, resulted in decreased expression of intestinal stem cell markers and impaired regeneration of ulcerated colon epithelium. Adenocarcinomas with aberrant Wnt signaling arose with similar incidence in wild-type and mutant mice. However, transcriptional profiles were vastly different: Whereas wild-type tumors displayed characteristics of epithelial-mesenchymal transition (EMT) and stem cell-like properties, these properties were largely abrogated in mutant tumors. These findings reveal an essential role for Bcl9/Bcl9l in regulating a subset of Wnt target genes involved in controlling EMT and stem cell-related features and suggest that targeting the Bcl9/Bcl9l arm of Wnt signaling in Wnt-activated cancers might attenuate these traits, which are associated with tumor invasion, metastasis, and resistance to therapy.
Early and late complications after endoscopic sphincterotomy for biliary lithiasis with and without the gall bladder 'in situ'.
Authors: J Escourrou, J A Cordova, F Lazorthes, J Frexinos, A Ribet
Journal: Gut (1984)

Endoscopic sphincterotomy has gained wide acceptance in the treatment of biliary lithiasis. We attempted endoscopic sphincterotomy in 443 patients and were successful in 407 (92%). Sphincterotomy was carried out with the gall bladder in situ in 234 cases (57%) of advanced age or high surgical risk. Immediate complications occurred in 7%, of which haemorrhage was the most frequent. The mortality rate was 1.5%. Three hundred and sixteen endoscopic sphincterotomies were performed more than six months before writing and follow up was available for 226 (72%) from six to 78 months. Late complications were observed in 16 patients with gall bladder 'in situ' (12%); the most frequent was cholecystitis in 6%. In five patients of the group without gall bladder, four had cholangitis related to retained or recurrent stones, and one restenosed . No episodes of cholangitis were observed in patients without stones despite reflux of barium up the biliary tree as observed during a barium meal examination.
Three-Dimensional Magnetic Resonance Cholangiopancreatography with Respiratory Triggering in the Diagnosis of Primary Sclerosing Cholangitis: Comparison with Endoscopic Retrograde Cholangiography
Authors: H. J. Textor, S. Flacke, D. Pauleit, E. Keller, M. Neubrand, B. Terjung, J. Gieseke, C. Scheurlen, T. Sauerbruch, H. H. Schild
Journal: Endoscopy (2002)

Background and Study Aims: The purpose of this study was to evaluate the accuracy of respiratory-triggered three-dimensional magnetic resonance cholangiopancreatography (3D-MRCP) for the detection of primary sclerosing cholangitis (PSC) and to compare the specific findings of magnetic resonance cholangiography and endoscopic retrograde cholangiography in patients with PSC. Patients and Methods: The MRCP findings were evaluated in 150 patients with clinical symptoms (progressive fatigue, pruritus followed by icterus) and/or elevated values for alkaline phosphatase and serum aspartate transaminase, and occasionally an elevated serum concentration of bilirubin as a sign of cholestasis, who were consecutively referred for magnetic resonance imaging. Two observers independently classified bile duct abnormalities and established the MRCP diagnosis in a consensus reading. The results of MRCP were compared with the definitive diagnosis, which was based on the clinical history and laboratory and histological data, as well as on endoscopic retrograde cholangio-pancreatography (ERCP) findings. In a second step, the observers compared the delineation of the biliary system and morphological findings using MRCP and ERCP in patients with confirmed PSC. Results: Diagnostic examinations were obtained in 146 of the 150 MRCPs (97 %). The diagnosis of PSC was confirmed by clinical data and ERCP in 34 of these 150 patients (23 %). The sensitivity and specificity of MRCP for diagnosing PSC were 88 % (29 of 33) and 99 % (108 of 109), respectively. MRCP and ERCP yielded similar scores for the delineation of the biliary system (P = 0.2) in patients with PSC. However, different bile duct abnormalities leading to the diagnosis of PSC were depicted by MRCP and ERCP; more bile duct stenoses and pruning were seen with ERCP and more skip dilatation with MRCP (P < 10-4). Conclusion: In patients with PSC, MRCP is a highly sensitive method and its diagnostic accuracy is comparable to that of ERCP.
Antibodies to the Epidermal Growth Factor Receptor in Non–Small Cell Lung Cancer: Current Status of Matuzumab and Panitumumab
Authors: Mark A. Socinski
Journal: Clinical Cancer Research (2007)

Abstract Matuzumab and panitumumab are antibodies against the epidermal growth factor receptor (EGFR) that are being evaluated in several malignancies including non–small cell lung cancer (NSCLC). In phase I trials of single-agent matuzumab in patients with EGFR-positive cancer, three tumor responses were documented in esophageal squamous cell carcinoma as well as colorectal carcinoma. A phase I trial of matuzumab in combination with paclitaxel has been reported in 18 patients with EGFR-positive advanced NSCLC. Objective responses were seen in 4 of 18 (23%) patients. A randomized phase II trial is currently ongoing in second-line NSCLC with matuzumab in combination with pemetrexed. A large dose/schedule trial of single-agent panitumumab enrolled 96 patients with EGFR-positive solid tumors. No responses were seen in the 14 lung cancer patients evaluated; 5 of 39 patients with colorectal cancers had objective responses. A randomized phase II trial of carboplatin/paclitaxel with or without panitumumab in 166 patients with previously untreated advanced stage IIIB/IV NSCLC did not find any benefit for the panitumumab arm compared with the chemotherapy alone arm with regard to response rates, time to disease progression, or median survival time. The lack of a biomarker to identify a subset of NSCLC patients who may derive benefit from this agent limits any potential enthusiasm for further trials of panitumumab at this time in NSCLC.
A multicenter phase II trial of intrathecal topotecan in patients with meningeal malignancies
Authors: Morris D. Groves, Michael J. Glantz, Marc C. Chamberlain, Karen E. Baumgartner, Charles A. Conrad, Sigmund Hsu, Jeffrey Scott Wefel, Mark R. Gilbert, Sandra Ictech, Kathy U. Hunter, Arthur D. Forman, Vinay K. Puduvalli, Howard Colman, Kenneth R Hess, W K Alfred Yung
Journal: Neuro-Oncology (2008)

To determine the therapeutic efficacy (13-week and 26-week CNS progression-free survival [PFS], response rate, and overall survival) and safety of intraventricular (IVent) topotecan in patients with neoplastic meningitis (NM), we conducted a phase II, open-label, nonrandomized, single-arm trial of IVent topotecan in patients with NM using 400 mug of topotecan IVent twice weekly for 6 weeks, followed by evaluation with imaging, cerebrospinal fluid (CSF), and physical examinations. In the absence of disease progression, patients were then treated with IVent topotecan weekly for 6 weeks, twice monthly for 4 months, and monthly thereafter. Sixty-two patients (23 males and 39 females) were enrolled from April 2001 through March 2006. Median age and KPS at enrollment were 56 (range 5-83) and 80 (range 60-100), respectively. Primary cancers included breast (19), lung (13), CNS (14), and others (16). Forty patients (65%) completed the 6-week induction period, among whom 13 (21%) had CSF clearance of malignant cells. Kaplan-Meier estimates of PFS at 13 and 26 weeks were 30% (95% confidence interval [CI], 20%-45%) and 19% (95% CI, 11%-34%). Overall median survival (50 deaths) was 15 weeks (95% CI, 13-24 weeks). The most common side effect was chemical meningitis in 32% of patients (5% grade 3); 32% experienced no drug side effects. IVent topotecan is well tolerated, but provides no added benefit over other IVent therapies. Because of its modest side effect profile, combining IVent topotecan with other IVent or systemic interventions should be considered.
Long-term Antithyroid Treatment in Hyperthyroidism
Authors: D. Ward Slingerland
Journal: JAMA (1979)

The major drawback to treatment of hyperthyroidism with antithyroid compounds is the reported low rate of remission. Eighty patients have been given long-term (at least one year; average, 4.4 years; range, one to 14 years) continuous treatment with a remission rate of 76% and an average follow-up of 7.8 years (one to 21 years). The prognostic test of suppressed uptake by the thyroid of less than 20% was about 75% accurate in predicting continuing remission when treatment was stopped. Of those in remission, 14 (23%) were treated for one year, 35 (57%) for one to five years, and 12 (20%) for more than five years. Mild reactions occurred in five (6%), hypothyroidism in two (3%). An antithyroid drug is safe and effective therapy for hyperthyroidism. (<i>JAMA</i>242:2408-2410, 1979)
Abstract 3926: Chronic inflammatory levels of nitric oxide/reactive nitrogen species downregulate BRCA1 protein expression
Authors: Vasily A. Yakovlev
Journal: Cancer Research (2011)

Abstract The link between inflammation and cancer was proposed more than 150 years ago when Virchow suggested that malignancies tend to arise at sites of chronic inflammation. Recent studies have established that elevated levels of nitric oxide/reactive nitrogen species (NO/RNS) generated in the inflammatory microenvironment are associated with several conditions critical for initiation and promotion of cancer. The BRCA1 protein contributes to cell viability in multiple ways, including DNA repair, cell cycle checkpoint control, transcription, and regulation of chromosome segregation. Hundreds of mutations in the BRCA1 gene have been identified and associated with an increased risk of cancer. Sporadic breast carcinomas, on the other hand, rarely show mutations of this gene. Instead, BRCA1 protein expression is frequently reduced in sporadic cases. As sporadic tumors account for &amp;gt;90% of the breast cancer, considerable research is directed towards the identification of mechanisms that down-regulate the function of the wild type BRCA1 and lead to genetic instability. BRCA1 expression is negatively regulated at the transcriptional level by the repressive complex of retinoblastoma-like protein 2 (RBL2) and E2F4. Formation of the repression RBL2/E2F4 complex can be accelerated by, for example, RBL2 dephosphorylation. Recently, protein phosphatase 2A (PP2A), an enzyme responsible for RBL2 dephosphorylation, was shown to be nitrated and activated by NO/RNS (Ohama T., et al., JBC 285, 8711-18, 2010). In the present investigation I demonstrate that inflammatory levels of NO/RNS induce substantial dephosphorylation of RBL2. Normal human mammary epithelial cells (MCF-10A) were incubated with 0.1 mM of the NO-donor SNAP for 6 h. This concentration of NO-donor mimics the intracellular level of NO/RNS during chronic inflammation, hypoxia, and does not induce significant DNA damage and maintains the ATM/ATR-dependent pathways intact. After 6 h incubation with SNAP, significant decrease in total amount of BRCA1 protein was observed with no apparent changes in the levels of E2F1, E2F4, and the catalytic subunit of PP2A, all involved in the regulation of BRCA1. RBL2 dephosphorylation promotes a repressive RBL2/E2F4 complex formation, which inhibits expression of BRCA1. I hypothesize that NO/RNS generated by chronic inflammatory conditions posttranslationally modify proteins involved in the regulation of BRCA1 expression and downregulate BRCA1 expression, thereby constituting a critical role in genetic instability and ultimately carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3926. doi:10.1158/1538-7445.AM2011-3926
Short-term Prognosis After Emergency Department Diagnosis of TIA
Authors: S. Claiborne Johnston
Journal: JAMA (2000)

Context Management of patients with acute transient ischemic attack (TIA) varies widely, with some institutions admitting all patients and others proceeding with outpatient evaluations.Defining the short-term prognosis and risk factors for stroke after TIA may provide guidance in determining which patients need rapid evaluation.Objective To determine the short-term risk of stroke and other adverse events after emergency department (ED) diagnosis of TIA. Design and SettingCohort study conducted from March 1997 through February 1998 in 16 hospitals in a health maintenance organization in northern California.Patients A total of 1707 patients (mean age, 72 years) identified by ED physicians as having presented with TIA.Main Outcome Measures Risk of stroke during the 90 days after index TIA; other events, including death, recurrent TIA, and hospitalization for cardiovascular events. ResultsDuring the 90 days after index TIA, 180 patients (10.5%) returned to the ED with a stroke, 91 of which occurred in the first 2 days.Five factors were independently associated with stroke: age greater than 60 years (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.7;P = .01),diabetes mellitus (OR, 2.0; 95% CI, 1.4-2.9;PϽ.001), symptom duration longer than 10 minutes (OR, 2.3; 95% CI, 1.3-4.2;P=.005), weakness (OR, 1.9; 95% CI, 1.4-2.6;PϽ.001), and speech impairment (OR, 1.5; 95% CI, 1.1-2.1;P = .01).Stroke or other adverse events occurred in 428 patients (25.1%) in the 90 days after the TIA and included 44 hospitalizations for cardiovascular events (2.6%), 45 deaths (2.6%), and 216 recurrent TIAs (12.7%). ConclusionsOur results indicate that the short-term risk of stroke and other adverse events among patients who present to an ED with a TIA is substantial.Characteristics of the patient and the TIA may be useful for identifying patients who may benefit from expeditious evaluation and treatment.
Urea Excretion Rate as a Contributor to Trimethoprim-induced Hyperkalemia
Authors: Martin Schreiber, Mitchell L. Halperin
Journal: Annals of Internal Medicine (1994)

Letters15 January 1994Urea Excretion Rate as a Contributor to Trimethoprim-induced HyperkalemiaMartin Schreiber, MD and Mitchell L. Halperin, MDMartin Schreiber, MDSt. Michael's Hospital; University of Toronto; 38 Shuter Street; Toronto M5B 1A6, OntarioSearch for more papers by this author and Mitchell L. Halperin, MDSt. Michael's Hospital; University of Toronto; 38 Shuter Street; Toronto M5B 1A6, OntarioSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-2-199401150-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Velazquez and colleagues [1] and Greenberg and associates [2] have made valuable contributions to our understanding of the incidence and mechanisms of trimethoprim-induced hyperkalemia in patients with the acquired immunodeficiency syndrome (AIDS) and Pneumocystis carinii pneumonia.What remains unclear, however, is why hyperkalemia develops in only a subset of patients who are exposed to equivalent doses of trimethoprim. Other obvious contributing factors to hyperkalemia were not identified.We suggest the following potential mechanism. Renal potassium (K+) excretion depends not only on the ability to have a high K+ concentration in the lumen of the distal nephron, but ...References1. Velazquez H, Perazella MA, Wright FS, Ellison DH. Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med. 1993; 119:296-301. Google Scholar2. Greenberg S, Reiser IW, Chou SY, Porush JG. Trimethoprim-sulfamethoxazole induces reversible hyperkalemia. Ann Intern Med. 1993; 119:291-5. Google Scholar3. Vasuvattakul S, Quaggin SE, Scheich AM, Bayoumi A, Goguen JM, Cheema-Dhadli S, et al. Kaliuretic response to aldosterone: influence of the content of potassium in the diet. Am J Kidney Dis. 1993; 21: 152-60. Google Scholar4. de Veber H, Quaggin S, Scheich A, Steele A, Halperin ML. What is responsible for the diurnal pattern of K excretion? Clin Invest Med. 1993 (In press). Google Scholar Author, Article, and Disclosure InformationAffiliations: St. Michael's Hospital; University of Toronto; 38 Shuter Street; Toronto M5B 1A6, Ontario PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByClinical Disorders of HyperkalemiaDisorders of Plasma Potassium ConcentrationClinical Disorders of HyperkalemiaTrimethoprim-Induced Exacerbation of Hyperkalemia in a Dog with HypoadrenocorticismEffect of Standard-Dose Trimethoprim/Sulfamethoxazole on the Serum Potassium Concentration in Elderly MenAntikaliuretic action of trimethoprim is minimized by raising urine pH 15 January 1994Volume 120, Issue 2Page: 166-167KeywordsAIDSAttentionExcretionNephronsPotassiumProteinsSaltsSodiumUreaUrine Issue Published: 15 January 1994 CopyrightCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Prostate-Specific Antigen (PSA) Isoform p2PSA in Combination with Total PSA and Free PSA Improves Diagnostic Accuracy in Prostate Cancer Detection
Authors: Flip H. Jansen, Ron H.N. van Schaik, Joep Kurstjens, Wolfgang Horninger, Helmut Klocker, Jasmin Bektic, Mark F. Wildhagen, Monique J. Roobol, Chris H. Bangma, Georg Bartsch
Journal: European Urology (2010)
N-Cadherin Signaling Potentiates Mammary Tumor Metastasis via Enhanced Extracellular Signal-Regulated Kinase Activation
Authors: James Hulit, Kimita Suyama, Su Chung, Rinat Keren, Georgia Agiostratidou, Weisong Shan, Xinyuan Dong, Terence M. Williams, Michael P. Lisanti, Karen Knudsen, Rachel B. Hazan
Journal: Cancer Research (2007)

Abstract N-cadherin is up-regulated in aggressive breast carcinomas, but its mechanism of action in vivo remains unknown. Transgenic mice coexpressing N-cadherin and polyomavirus middle T antigen (PyVmT) in the mammary epithelium displayed increased pulmonary metastasis, with no differences in tumor onset or growth relative to control PyVmT mice. PyVmT-N-cadherin tumors contained higher levels of phosphorylated extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) than PyVmT controls, and phosphorylated ERK staining was further increased in pulmonary metastases. Tumor cell isolates from PyVmT-N-cadherin mice exhibited enhanced ERK activation, motility, invasion, and matrix metalloproteinase-9 (MMP-9) expression relative to PyVmT controls. MAPK/ERK kinase 1 inhibition in PyVmT-N-cadherin cells reduced MMP-9 production and invasion but not motility. Furthermore, inactivation of fibroblast growth factor receptor in PyVmT-N-cadherin cells reduced motility, invasion, and ERK activation but had no effect on PyVmT cells. Thus, de novo expression of N-cadherin in mammary ducts enhances metastasis of breast tumors via enhanced ERK signaling. [Cancer Res 2007;67(7):3106–16]
Lack of Primary Cilia Primes Shear-Induced Endothelial-to-Mesenchymal Transition
Authors: Anastasia D. Egorova, Padmini P.S.J. Khedoe, Marie-José T.H. Goumans, Bradley K. Yoder, Surya M. Nauli, Peter ten Dijke, Robert E. Poelmann, Beerend P. Hierck
Journal: Circulation Research (2011)

Primary cilia are cellular protrusions that serve as mechanosensors for fluid flow. In endothelial cells (ECs), they function by transducing local blood flow information into functional responses, such as nitric oxide production and initiation of gene expression. Cilia are present on ECs in areas of low or disturbed flow and absent in areas of high flow. In the embryonic heart, high-flow regime applies to the endocardial cushion area, and the absence of cilia here coincides with the process of endothelial-to-mesenchymal transition (EndoMT).In this study, we investigated the role of the primary cilium in defining the responses of ECs to fluid shear stress and in EndoMT.Nonciliated mouse embryonic ECs with a mutation in Tg737/Ift88 were used to compare the response to fluid shear stress to that of ciliated ECs. In vitro, nonciliated ECs undergo shear-induced EndoMT, which is accompanied by downregulation of Klf4. This Tgfβ/Alk5-dependent transformation is prevented by blocking Tgfβ signaling, overexpression of Klf4, or rescue of the primary cilium. In the hearts of Tg737(orpk/orpk) embryos, Tgfβ/Alk5 signaling was activated in areas in which ECs would normally be ciliated but now lack cilia because of the mutation. In these areas, ECs show increased Smad2 phosphorylation and expression of α-smooth muscle actin.This study demonstrates the central role of primary cilia in rendering ECs prone to shear-induced activation of Tgfβ/Alk5 signaling and EndoMT and thereby provides a functional link between primary cilia and flow-related endothelial performance.