tbuckley/cabot-search huggingface dataset:
Requiem for Digoxin?
Authors: Jacob Zatuchni
Journal: Annals of Internal Medicine (1991)

Letters1 June 1991Requiem for Digoxin?Jacob Zatuchni, MDJacob Zatuchni, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-114-11-993_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:Falk and Leavitt (1) would like to sound the death knell for digoxin as therapy for atrial fibrillation. They cannot understand why the drug has been popular for 200 years and conclude that it must be because of mythology and not science. Although aware of the beneficial effects of digoxin in patients with atrial fibrillation, they choose to emphasize its questionable use for prevention of atrial fibrillation in patients who have reverted to sinus rhythm, the possibility that digoxin makes recurrences of atrial fibrillation worse, and the questionable significance of tachycardia during exercise if it occurs. They...References1. FalkLeavitt RJ. Digoxin for atrial fibrillation: a drug whose time has gone? Ann Intern Med. 1991;114:573-5. LinkGoogle Scholar2. PritchettMcCarthyWilkinson EEW. Propafenone treatment of symptomatic paroxysmal supraventricular arrhythmias. Ann Intern Med. 1991;114:539-44. LinkGoogle Scholar3. PietersenHellemann AH. Usefulness of flecainide for prevention of paroxysmal atrial fibrillation and flutter. Am J Cardiol. 1991;67:713-7. CrossrefMedlineGoogle Scholar4. CoplenAntmanBerlinHewittChalmers SEJPT. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion. Circulation. 1990;82:1106-16. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Jacob Zatuchni, MDAffiliations: Pennsylvania Hospital Philadelphia, PA 19139 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDigoxin: Mythology or Evidence?Rodney H. Falk, MD 1 June 1991Volume 114, Issue 11Page: 993-993KeywordsAtrial fibrillationDrugsExerciseTachycardia ePublished: 1 December 2008 Issue Published: 1 June 1991 PDF downloadLoading ...
The PROPKD Score
Authors: Emilie Cornec-Le Gall, Marie-Pierre Audrézet, Annick Rousseau, Maryvonne Hourmant, Eric Renaudineau, Christophe Charasse, Marie-Pascale Morin, Marie-Christine Moal, Jacques Dantal, Bassem Wehbe, Régine Perrichot, Thierry Frouget, Cécile Vigneau, Jérôme Potier, Philippe Jousset, Marie-Paule Guillodo, Pascale Siohan, Nazim Terki, Théophile Sawadogo, Didier Legrand, Victorio Menoyo-Calonge, Seddik Benarbia, Dominique Besnier, Hélène Longuet, Claude Férec, Yannick Le Meur
Journal: Journal of the American Society of Nephrology (2015)

The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0–3 points), intermediate risk (4–6 points), and high risk (7–9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.
Update on the Role of Interleukin 2 and Other Cytokines in the Treatment of Patients with Stage IV Renal Carcinoma
Authors: Michael B. Atkins, Meredith Regan, David McDermott
Journal: Clinical Cancer Research (2004)

Immunoreactive cytokines have been the mainstay of treatment of renal cancer for the past 15 years. Most research has focused on interferon alpha (IFN-alpha) and interleukin 2 (IL-2). IFN-alpha has been shown in Phase III studies to produce a modest survival advantage over inactive or non-IFN-containing regimens. Its general tolerability, multiple proposed mechanisms of action, and familiarity have prompted IFN-alpha to be studied in combination with a variety of agents with potential activity against renal cell carcinoma. These various studies may justify an increased role for IFN-alpha in the treatment of renal cancer in the foreseeable future. High-dose bolus IL-2 remains the only treatment for stage IV renal cancer approved by the United States Food and Drug Administration. Food and Drug Administration approval was granted in 1992 based on the ability of this agent to produce durable complete responses in a small number of patients. Unfortunately, the toxicity, expense, and restricted accessibility of high-dose IL-2 make it a poor standard. Regimens involving lower doses of IL-2 either alone or in combination with IFN-alpha have generally produced fewer tumor regressions of less overall quality. Recent efforts have focused on trying to identify factors predictive of response to IL-2 therapy so that this treatment could be limited to those most likely to benefit.
Potential opportunity in the development of new therapeutic agents based on endogenous and exogenous inhibitors of the proprotein convertases
Authors: Yannick Bontemps, Nathalie Scamuffa, Fabien Calvo, Abdel‐Majid Khatib
Journal: Medicinal Research Reviews (2006)

Abstract The proprotein convertases (PCs) are responsible for the endoproteolytic processing of various protein precursors (e.g., growth factors, receptors, adhesion molecules, and matrix metalloproteinases) implicated in several diseases such as obesity, diabetes, atherosclerosis, cancer, and Alzheimer disease. The potential clinical and pharmacological role of the PCs has fostered the development of various PC‐inhibitors. In this review we summarized the recent findings on PCs inhibitors, their mode of actions and potential use in the therapy of various diseases. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 5, 631–648, 2007
Premature ventricular complex-induced chronic cough and cough syncope
Authors: S. Stec, M. Da̧browska, B. Zaborska, P. Bielicki, M. Maskey-Warzęchowska, W. Tarnowski, R. Chazan, P. Kulakowski
Journal: European Respiratory Journal (2007)

The present case study reports a case of chronic cough and cough syncope associated with frequent premature ventricular complexes (PVCs). Careful analysis of cough-related symptoms and ECG monitoring led to the suspicion of PVC-induced cough. A coincidence between PVCs and episodes of cough was also documented by a portable multichannel recorder. Moreover, Doppler echocardiography revealed a PVC-induced transient increase in the pulmonary artery blood flow. After exclusion of other possible aetiologies, complete relief of chronic cough and cough syncope was achieved by radiofrequency ablation of the arrhythmogenic focus located in the right ventricular outflow tract. Premature ventricular complexes should be considered as a cause of chronic cough and cough syncope and an interdisciplinary cooperation can lead to successful diagnosis and treatment of this condition.
Dual-Color Imaging of Nuclear-Cytoplasmic Dynamics, Viability, and Proliferation of Cancer Cells in the Portal Vein Area
Authors: Kazuhiko Tsuji, Kensuke Yamauchi, Meng Yang, Ping Jiang, Michael Bouvet, Hitoshi Endo, Yoshikatsu Kanai, Koji Yamashita, Abdool R. Moossa, Robert M. Hoffman
Journal: Cancer Research (2006)

Abstract We used dual-color in vivo cellular imaging to visualize trafficking, nuclear-cytoplasmic dynamics, and the viability of cancer cells after their injection into the portal vein of mice. For these studies, we used dual-color fluorescent cancer cells that express green fluorescent protein (GFP) linked to histone H2B in the nucleus and retroviral red fluorescent protein (RFP) in the cytoplasm. Human HCT-116-GFP-RFP colon cancer and mouse mammary tumor (MMT) cells were HCT-116-GFP-RFP in the portal vein of nude mice. The cells were observed intravitally in the liver at the single-cell level using the Olympus OV100 whole-mouse imaging system. Most HCT-116-GFP-RFP cells remained in sinusoids near peripheral portal veins. Only a small fraction of the cancer cells invaded the lobular area. Extensive clasmocytosis (destruction of the cytoplasm) of the HCT-116-GFP-RFP cells occurred within 6 hours. The number of apoptotic cells rapidly increased within the portal vein within 12 hours of injection. Apoptosis was readily visualized in the dual-color cells by their altered nuclear morphology. The data suggest rapid death of HCT-116-GFP-RFP cells in the portal vein. In contrast, dual-color MMT-GFP-RFP cells injected into the portal vein mostly survived in the liver of nude mice 24 hours after injection. Many surviving MMT-GFP-RFP cells showed invasive figures with cytoplasmic protrusions. The cells grew aggressively and formed colonies in the liver. However, when the host mice were pretreated with cyclophosphamide, the HCT-116-GFP-RFP cells also survived and formed colonies in the liver after portal vein injection. These results suggest that a cyclophosphamide-sensitive host cellular system attacked the HCT-116-GFP-RFP cells but could not effectively kill the MMT-GFP-RFP cells. (Cancer Res 2006; 66(1): 303-6)
Mechanical Stretch Activates the JAK/STAT Pathway in Rat Cardiomyocytes
Authors: Jing Pan, Keiichi Fukuda, Mikiyoshi Saito, Junichi Matsuzaki, Hiroaki Kodama, Motoaki Sano, Toshiyuki Takahashi, Takahiro Kato, Satoshi Ogawa
Journal: Circulation Research (1999)

Abstract —This study was designed to determine whether mechanical stretch activates the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway in cardiomyocytes and, if so, by what mechanism. Neonatal rat/murine cardiomyocytes were cultured on malleable silicone dishes and were stretched by 20%. Mechanical stretch induced rapid phosphorylation of JAK1, JAK2, Tyk2, STAT1, STAT3, and glycoprotein 130 as early as 2 minutes and peaked at 5 to 15 minutes. It also caused gel mobility shift of sis-inducing element, which was supershifted by preincubation with anti-STAT3 antibody. Preincubation with CV11974 (AT 1 blocker) partially inhibited the phosphorylation of STAT1, but not that of STAT3. Preincubation with TAK044 (endothelin-1-type A/B-receptor blocker) did not attenuate this pathway. RX435 (anti–glycoprotein 130 blocking antibody) inhibited the phosphorylation of STAT3 and partially inhibited that of STAT1. Phosphorylation of STAT1 and STAT3 was strongly inhibited by HOE642 (Na + /H + exchanger inhibitor) and BAPTA-AM (intracellular calcium chelator), but not by gadolinium (stretch-activated ion channel inhibitor), EGTA (extracellular Ca 2+ chelator), or KN62 (Ca 2+ /calmodulin kinase II inhibitor). Chelerythrine (protein kinase C inhibitor) partially inhibited the phosphorylation of STAT1 and STAT3. Mechanical stretch also augmented the mRNA expression of cardiotrophin-1, interleukin-6, and leukemia inhibitory factor at 60 to 120 minutes. These results indicated that the JAK/STAT pathway was activated by mechanical stretch, and that this activation was partially dependent on autocrine/paracrine–secreted angiotensin II and was mainly dependent on the interleukin-6 family of cytokines but was independent of endothelin-1. Moreover, certain levels of intracellular Ca 2+ were necessary for stretch-induced activation of this pathway, and protein kinase C was also partially involved in this activation.
Coronary artery size and dilating capacity in ultradistance runners.
Authors: W L Haskell, C Sims, J Myll, W M Bortz, F G St Goar, E L Alderman
Journal: Circulation (1993)

BACKGROUND Increases in coronary artery size and dilating capacity have been observed in some animals after endurance training, and at autopsy, active men appear to have enlarged epicardial coronary arteries. This cross-sectional study was designed to test the hypothesis that highly trained endurance runners have larger epicardial coronary arteries and greater dilating capacity than inactive men. METHODS AND RESULTS The subjects, ages 39-66 years, included 11 male volunteers who had participated in ultradistance running during the past 2 years and 11 physically inactive men who had been referred for arteriography but had no visible coronary artery disease. The internal diameter of the proximal segments of each major epicardial coronary artery was measured before and after nitroglycerin administration using a computer-based quantitative arteriographic analysis system. Measurements also included maximal oxygen uptake, plasma lipoprotein concentrations, body composition, and cardiac mass by echocardiography. Before nitroglycerin, the sum of the cross-sectional areas for the proximal right, left anterior descending, and circumflex arteries was not different for the runners and the inactive men: 22.7 +/- 4.79 versus 21.0 +/- 7.97 mm2 (p = 0.57), respectively. However, the increase in the sum of the cross-sectional area for the proximal right, left anterior descending, and circumflex arteries in response to nitroglycerin was greater for the runners (13.20 +/- 4.76 versus 6.00 +/- 3.02 mm2; p = 0.002). Left ventricular mass index (152 +/- 21 versus 116 +/- 41 g/m2; p &lt; 0.05) but not left ventricular mass (284 +/- 40 versus 246 +/- 91 g; p = 0.22) was significantly greater for the runners. Among the runners, dilating capacity was positively correlated with aerobic capacity and negatively related to adiposity, resting heart rate, and plasma lipoprotein concentrations. CONCLUSIONS Highly trained, middle-aged endurance runners demonstrated a significantly greater dilating capacity of their epicardial coronary arteries in response to nitroglycerin compared with inactive men. The causes of this greater dilating capacity and its clinical significance need to be determined.
Economics of smoking cessation
Authors: Steve Parrott, Christine Godfrey
Journal: BMJ (2004)

Smoking imposes a huge economic burden on society—currently up to 15% of total healthcare costs in developed countries. Smoking cessation can save years of life, at a very low cost compared with alternative interventions. This chapter reviews some of the economic aspects of smoking cessation.



Self rated health status (100 = best imaginable health state), by age and smoking status. Data from Kind et al. UK population norms for EQ-5D. York: Centre for Health Economics (Discussion paper 172)



The most obvious benefits of smoking cessation are improvements in life expectancy and prevention of disease. However, cessation also improves individuals' quality of life as smokers tend to have a lower self reported health status than non-smokers, and this improves after stopping smoking. 

View this table:

Benefits of smoking cessation



There are also wider economic benefits to individuals and society, arising from reductions in the effects of passive smoking in non-smokers and savings to the health service and the employer. These wider benefits are often omitted from economic evaluations of cessation interventions, which consequently tend to underestimate the true value for money afforded by such programmes.

Many estimates have been made of the economic cost of smoking in terms of health resources. For the United States they typically range from about 0.6% to 0.85% of gross domestic product. In absolute terms, the US public health service estimates a total cost of $50bn (£29bn;€42bn) a year for the treatment of smoking related diseases, in addition to an annual $47bn in lost earnings and productivity. Estimated total costs in Australia and Canada, as a proportion of their gross domestic product, are 0.4% and 0.56% respectively. In the United Kingdom, the treatment of smoking related disease has been estimated to cost the NHS £1.4bn-£1.5bn a year (about 0.16% of the gross domestic product)—including £127m to treat lung cancer …
Denosumab in treatment-naïve and pre-treated with zoledronic acid postmenopausal women with low bone mass: Effect on bone mineral density and bone turnover markers
Authors: Athanasios D. Anastasilakis, Stergios A. Polyzos, Zoe A. Efstathiadou, Matthaios Savvidis, Grigorios T. Sakellariou, Athanasios Papatheodorou, Panagiotis Kokkoris, Polyzois Makras
Journal: Metabolism (2015)
Postcolonoscopy colorectal cancers are preventable: a population-based study
Authors: Chantal M C le Clercq, Mariëlle W E Bouwens, Eveline J A Rondagh, C Minke Bakker, Eric T P Keulen, Rogier J de Ridder, Bjorn Winkens, Ad A M Masclee, Silvia Sanduleanu
Journal: Gut (2013)

<h3>Objective</h3> The quality of colonoscopy is key for ensuring protection against colorectal cancer (CRC). We therefore aimed to elucidate the aetiology of postcolonoscopy CRCs (PCCRCs), and especially to identify preventable factors. <h3>Methods</h3> We conducted a population-based study of all patients diagnosed with CRC in South-Limburg from 2001 to 2010 using colonoscopy and histopathology records and data from the Netherlands Cancer Registry. PCCRCs were defined as cancers diagnosed within 5 years after an index colonoscopy. According to location, CRCs were categorised into proximal or distal from the splenic flexure and, according to macroscopic aspect, into flat or protruded. Aetiological factors for PCCRCs were subdivided into procedure-related (missed lesions, inadequate examination/surveillance, incomplete resection) and biology-related (new cancers). <h3>Results</h3> We included a total of 5107 patients with CRC, of whom 147 (2.9% of all patients, mean age 72.8 years, 55.1% men) had PCCRCs diagnosed on average 26 months after an index colonoscopy. Logistic regression analysis, adjusted for age and gender, showed that PCCRCs were significantly more often proximally located (OR 3.92, 95% CI 2.71 to 5.69), smaller in size (OR 0.78, 95% CI 0.70 to 0.87) and more often flat (OR 1.70, 95% CI 1.18 to 2.43) than prevalent CRCs. Of the PCCRCs, 57.8% were attributed to missed lesions, 19.8% to inadequate examination/surveillance and 8.8% to incomplete resection, while 13.6% were newly developed cancers. <h3>Conclusions</h3> In our experience, 86.4% of all PCCRCs could be explained by procedural factors, especially missed lesions. Quality improvements in performance of colonoscopy, with special attention to the detection and resection of proximally located flat precursors, have the potential to prevent PCCRCs.
Hypertonicity Compromises Renal Mineralocorticoid Receptor Signaling through Tis11b-Mediated Post-Transcriptional Control
Authors: Say Viengchareun, Ingrid Lema, Khadija Lamribet, Vixra Keo, Anne Blanchard, Nadia Cherradi, Marc Lombès
Journal: Journal of the American Society of Nephrology (2014)

The mineralocorticoid receptor (MR) mediates the Na+-retaining action of aldosterone. MR is highly expressed in the distal nephron, which is submitted to intense variations in extracellular fluid tonicity generated by the corticopapillary gradient. We previously showed that post-transcriptional events control renal MR abundance. Here, we report that hypertonicity increases expression of the mRNA-destabilizing protein Tis11b, a member of the tristetraprolin/ZFP36 family, and thereby, decreases MR expression in renal KC3AC1 cells. The 3′-untranslated regions (3′-UTRs) of human and mouse MR mRNA, containing several highly conserved adenylate/uridylate-rich elements (AREs), were cloned downstream of a reporter gene. Luciferase activities of full-length or truncated MR Luc-3′-UTR mutants decreased drastically when cotransfected with Tis11b plasmid, correlating with an approximately 50% shorter half-life of ARE-containing transcripts. Using site-directed mutagenesis and RNA immunoprecipitation, we identified a crucial ARE motif within the MR 3′-UTR, to which Tis11b must bind for destabilizing activity. Coimmunoprecipitation experiments suggested that endogenous Tis11b physically interacts with MR mRNA in KC3AC1 cells, and Tis11b knockdown prevented hypertonicity-elicited repression of MR. Moreover, hypertonicity blunted aldosterone-stimulated expression of glucocorticoid-induced leucine-zipper protein and the α-subunit of the epithelial Na+ channel, supporting impaired MR signaling. Challenging the renal osmotic gradient by submitting mice to water deprivation, diuretic administration, or high-Na+ diet increased renal Tis11b and decreased MR expression, particularly in the cortex, thus establishing a mechanistic pathway for osmotic regulation of MR expression in vivo. Altogether, we uncovered a mechanism by which renal MR expression is regulated through mRNA turnover, a post-transcriptional control that seems physiologically relevant.
Chemokines and Chemokine Receptors in Lymphoid Tissue Dynamics
Authors: Olga Schulz, Swantje I. Hammerschmidt, G. Leandros Moschovakis, Reinhold Förster
Journal: Annual Review of Immunology (2016)

The continuous migration of immune cells between lymphoid and nonlymphoid organs is a key feature of the immune system, facilitating the distribution of effector cells within nearly all compartments of the body. Furthermore, reaching their correct position within primary, secondary, or tertiary lymphoid organs is a prerequisite to ensure immune cells' unimpaired differentiation, maturation, and selection, as well as their activation or functional silencing. The superfamilies of chemokines and chemokine receptors are of major importance in guiding immune cells to and within lymphoid and nonlymphoid tissues. In this review we focus on the role of the chemokine system in the migration dynamics of immune cells within lymphoid organs at the steady state and on how these dynamics are affected by infectious and inflammatory processes.