tbuckley/cabot-search huggingface dataset:
Another Look at Induction Chemotherapy for Organ Preservation in Patients With Head and Neck Cancer
Authors: A. A. Forastiere
Journal: JNCI Journal of the National Cancer Institute (1996)

chemotherapy followed by radiotherapy as its new standard for comparison of future organ-sparing strategies. The EORTC trial design differed from other induction chemotherapy trials in some respects. First, only patients achieving a CR on endoscopic evaluation were offered organsparing therapy. One could speculate that this resulted in better local control (similar to surgically treated patients) than occurred in the VA Laryngeal Cancer Study that was less selective, allowing partial responders (PR) to receive radiotherapy. In reality, it is quite difficult to obtain accurate bidimensional measurements of a lesion visualized in the larynx or hypopharynx to document a PR. Second, endoscopy alone was used to clinically evaluate response after each course of chemotherapy; computed tomographic imaging was recommended but not required. Third, the decision to perform a neck dissection before radiotherapy for patients with a CR at the primary but residual disease in the neck was left to the treating physician, not mandated. These variances served to streamline the study, focusing on the main question of feasibility of organ preservation and survival, and do not detract from the results. This protocol used a well-establish ed chemotherapy regimen (cisplatin at 100 mg/m2 on day 1 + infusional 5-FU at 1000 mg/m2 per day for 5 days repeated every 3 weeks). The 86% response rate (54% CR + 32% PR) of the primary is in the expected range. Compliance was excellent: 95% of the patients (89 of 94) in the surgery arm received the planned treatment as did 93% of the patients (93 of 100) randomized to receive chemotherapy. Only six patients randomized to receive induction chemotherapy for whom surgery was recommended refused to undergo laryngopharyngectomy per protocol. There was one treatment-related death during induction chemotherapy and no increase in surgical complications after chemotherapy. The EORTC trial was well designed and executed. A uniform patient population with respect to site, stage, and operability was studied with the use of an optimal drug regimen. Furthermore, the sample size was adequate to formulate conclusions with
Are Spatial Memories Strengthened in the Human Hippocampus during Slow Wave Sleep?
Authors: Philippe Peigneux, Steven Laureys, Sonia Fuchs, Fabienne Collette, Fabien Perrin, Jean Reggers, Christophe Phillips, Christian Degueldre, Guy Del Fiore, Joël Aerts, André Luxen, Pierre Maquet
Journal: Neuron (2004)
The Economics and Politics of Health.
Journal: Annals of Internal Medicine (1983)

This study analyzes the entire health scene, providing valuable insights into the working of the health care practices, and offering policy recommendations for more effective distribution. Although the study focuses mainly on cost containment, it also explores the relationship between health and medical care, the expansion of the demand for medical care and the over-regulated supply, and the economic differences between emergency and nonemergency care.Originally published in 1985. A UNC Press Enduring Edition -- UNC Press Enduring Editions use the latest in digital technology to make available again books from our distinguished backlist that were previously out of print. These editions are published unaltered from the original, and are presented in affordable paperback formats, bringing readers both historical and cultural value.
Interleukin-1 Receptor Antagonist (IL-1RN) Genotype Modulates the Replicative Capacity of Human Endothelial Cells
Authors: Rachael M. Dewberry, David C. Crossman, Sheila E. Francis
Journal: Circulation Research (2003)

Endothelial cells (ECs) undergo a finite number of cell divisions before growth arrest or replicative senescence, modulated in part by the proinflammatory cytokine, interleukin-1 (IL-1). IL-1 and its family members are expressed in human atherosclerotic vessels, mainly in the endothelium. EC replicative senescence and IL-1 have been associated with atherosclerosis. Genetic variants at the IL-1 locus have been associated with a variety of coronary phenotypes. In this study, we examined the relationship between the interleukin-1 receptor antagonist variable number tandem repeat allele 2 (IL-1RN*2*2) and EC replicative capacity. A significant decrease in EC cumulative population doublings (CPDs) was associated with the rare allele (IL-1RN*2*2) at IL-1RN, 8.56+/-0.97 (n=7) versus 13.14+/-1.00 (IL-1RN*1*1, n=20), P=0.0118. Proliferation of IL-1RN*2*2 ECs detected by Ki67 expression was also significantly reduced particularly at later passage, passage 6: 21.76+/-0.93% (n=6) versus 48.10+/-8.81% (IL-1RN*1*1, n=7) (P=0.0323) and passage 8: 22.48+/-3.08% (n=6) versus 42.29+/-3.06% (IL-1RN*1*1, n=7) (P=0.0028). IL-1RN*2 carriage was associated with increased numbers of senescent ECs. Basal apoptosis, telomerase activity, and telomere length were not different with respect to IL-1RN genotype. Addition of exogenous IL-1ra (1 ng/mL) increased CPDs in a number of human umbilical vein endothelial cell cultures and increased proliferating cells from 12.11+/-1.21% to 27.82+/-2.82% (P=0.0216, IL-1RN*2*2, passage 8, n=2). These data suggest genetic control of EC proliferation and life span by the IL-1 locus and imply that IL-1ra may have a function connected with EC growth.
Pharmacology of Thyrotropin-Releasing Hormone
Authors: A Horita, M A Carino, H Lai
Journal: The Annual Review of Pharmacology and Toxicology (1986)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
Prevalence of Diagnosed Diabetes Among African-American and Non-Hispanic White Youth, 1999
Authors: John E. Oeltmann, Angela D. Liese, Howard J. Heinze, Cheryl L. Addy, Elizabeth J. Mayer-Davis
Journal: Diabetes Care (2003)

OBJECTIVE—To document diabetes prevalence among African-American and non-Hispanic white youth in a two-county region in South Carolina. RESEARCH DESIGN AND METHODS—We conducted a population-based surveillance effort to identify case subjects aged 0–18.9 years with a physician diagnosis of diabetes residing in a two-county region in 1999. Case subjects were ascertained from hospitals, the sole office of pediatric endocrinology, and several smaller sources. Case subjects were classified according to the diagnosis made by a pediatric endocrinologist. As a completeness check, eight randomly selected physicians were queried for eligible case subjects. Capture-recapture provided an additional measure of completeness. Prevalence estimates used U.S. 2000 Census data for the two-county denominator. RESULTS—Crude total diabetes prevalence was 1.7 cases per 1,000 youth and similar between African-American and non-Hispanic white youth. Among younger youth (0–9.9 years), non-Hispanic white total prevalence was 1.1 per 1,000 and African-American prevalence was 0.6 per 1,000. Among older youth (10.0–18.9 years), non-Hispanic white total prevalence was 2.5 per 1,000 and African-American prevalence was 3.1 per 1,000. Type 2 diabetes was only confirmed among older prevalent cases. Ascertainment completeness was estimated to be 98%. CONCLUSIONS—Our estimates suggest that total diabetes prevalence among non-Hispanic white youth is similar to rates observed over 20 years ago. Among African-American youth, the difference in prevalence noted between younger and older age-groups was notably greater than that observed among the non-Hispanic white youth, potentially reflecting a more marked increase in diabetes incidence with age.
2′,7′-Dichlorofluorescein is not a probe for the detection of reactive oxygen and nitrogen species
Authors: Megan J Reiniers, Rowan F van Golen, Thomas M van Gulik, Michal Heger
Journal: Journal of Hepatology (2011)

In a recent issue of this Journal, Llacuna and colleagues [1] reported on the pivotal role of mitochondrial cholesterol accumulation and aggravated oxidative stress in the pathophysiology of ischemia–reperfusion (IR) injury in the fatty liver. Steatotic murine livers were subjected to 60min of warm ischemia followed by a non-specified period of reperfusion. During reperfusion, part of the liver was incubated for 45min with 200μM 2′,7′-dichlorofluorescein (DCF) by means of superfusion and subsequently imaged by in vivo confocal microscopy, whereby DCF fluorescence was considered a direct measure of reactive oxygen species (ROS) generation.
Multicenter Randomized Trial Comparing Sequential With Concomitant Administration of Doxorubicin and Docetaxel As First-Line Treatment of Metastatic Breast Cancer: A Spanish Breast Cancer Research Group (GEICAM-9903) Phase III Study
Authors: Emilio Alba, Miguel Martín, Manuel Ramos, Encarna Adrover, Ana Balil, Carlos Jara, Agustí Barnadas, Antonio Fernández-Aramburo, Pedro Sánchez-Rovira, Margarita Amenedo, Antonio Casado
Journal: Journal of Clinical Oncology (2004)

Purpose This randomized, multicenter, phase III trial evaluated whether sequential doxorubicin and docetaxel (A→T) reduced hematological toxicity, especially febrile neutropenia, compared with concomitant (AT) administration as first-line chemotherapy in metastatic breast cancer (MBC). Patients and Methods One hundred forty-four patients were randomly assigned to receive three cycles of doxorubicin 75 mg/m 2 every 21 days followed by three cycles of docetaxel 100 mg/m 2 , every 21 days (A→T) or six cycles of the combination doxorubicin 50 mg/m 2 and docetaxel 75 mg/m 2 (AT) every 21 days. Patients previously treated with anthracyclines received two cycles of doxorubicin followed by four cycles of docetaxel (A→T), or three cycles of AT followed by three cycles of docetaxel 100 mg/m 2 every 21 days. Results Febrile neutropenia was less common in the A→T arm (29.3% of patients, 6.9% of cycles) compared with the AT arm (47.8% of patients, 14.8% of cycles; P = .02 and P = .0004, respectively). Asthenia, diarrhea, and fever occurred more frequently in the AT arm. The overall responses rates were 61% in the A→T arm (95% CI, 50% to 72%) and 51% in the AT arm (95% CI, 39% to 63%). The median duration of response was 8.7 months (A→T) and 7.6 months (AT); the median time to progression was 10.5 months (A→T) and 9.2 months (AT); the median overall survival was 22.3 months (A→T) and 21.8 months (AT); and no significant differences were found. Conclusion A→T significantly reduced febrile neutropenia compared with AT in MBC patients and maintains comparable antitumoral efficacy. A→T represents a valid option for the treatment of MBC.
Sudden Cardiac Death, Genes, and Arrhythmogenesis
Authors: Peter M. Spooner, Christine Albert, Emelia J. Benjamin, Robin Boineau, Robert C. Elston, Alfred L. George, Xavier Jouven, Lewis H. Kuller, Jean W. MacCluer, Eduardo Marbán, James E. Muller, Peter J. Schwartz, David S. Siscovick, Russell P. Tracy, Wojciech Zareba, Douglas P. Zipes
Journal: Circulation (2001)

Malignant ventricular arrhythmias are the leading mechanism of death in patients with acute and chronic cardiac pathologies. The extent to which inherited mutations and polymorphic variation in genes determining arrhythmogenic mechanisms affect these patients remains unknown, but based on recent population studies, this risk appears significant, deserving much greater investigation. This report summarizes a National Heart, Lung, and Blood Institute workshop that considered sources of genetic variation that may contribute to sudden cardiac death in common cardiac diseases. Evidence on arrhythmogenic mechanisms in recent population studies suggests a significant portion of the risk of sudden cardiac death in such broad populations may be unrelated to traditional risk factors for predisposing conditions such as atherosclerosis, hypertension, and diabetes and instead may involve unrecognized genetic and environmental interactions that influence arrhythmic susceptibility more directly. Additional population and genetic studies directed at discovering the sources of inherited molecular risk that are most directly linked to arrhythmia initiation and propagation, in addition to studies on previously well-described risk factors, would appear to have considerable potential for reducing premature cardiovascular mortality.
PTU-046 Mind Over Matter? Gastrointestinal Bleeding Due To The Use Of Novel Oral Anticoagulants In Stroke Prevention
Authors: S Beg, J Patel, M Bhuva, D Collas, B Macfarlane
Journal: Gut (2014)

<h3>Introduction</h3> The occurrence of stroke secondary to the pro-thrombotic effects of AF is well recognised, with warfarinisation the established therapy for prevention. This is not without complications and so the introduction of the novel oral anticoagulants (NOAC), Dabigatran a factor IIa inhibitor and Rivaroxaban a Xa inhibitor have been received with enthusiasm. Advantages include single dosing, fewer drug interactions and freedom from monitoring, whilst data has demonstrated non-inferiority with respects to stroke prevention. A reported greater propensity to gastrointestinal (GI) bleeding is concerning given the lack of accepted reversal agents, in a cohort of patients who tend to be elderly with comorbidities. We aim to establish the GI complications associated with NOACs in stroke prevention. <h3>Methods</h3> We retrospectively analysed 170 consecutive patients from our TIA clinic, who were found to have AF. They were commenced on either Dabigatran or Rivaroxaban, with a total of 86 patient-years of exposure at the time of analysis. We interrogated our computer-based database to ascertain the incidence of anticoagulation related admissions and subsequent management <h3>Results</h3> Our cohort of 170 patients had a mean age of 76 years, with a male to female ratio of 8:9. Dabigatran at 220–300 mg/day was prescribed to 45% (n = 77), whilst 55% (n = 93) received Rivaroxaban 20–15 mg/day. Rivaroxaban was stopped in one patient due to drug induced hepatitis. One patient was switched from Dabigatran to Rivaroxaban due to dyspepsia. GI bleeds occurred in 5% (n = 4) of the Dabigatran group, with 2 upper and 2 lower GI bleeds, occurring on average after 25 days. These patients had a mean age of 84 years, with at least 2 comorbidities. Endoscopy revealed an oesophageal ulcer requiring clipping, new diagnosis of colorectal cancer, haemorrhoids and in one patient no cause was found. GI bleeding occurred in 1% (n = 1) of the Rivaroxaban group. The patient had a rectal bleed, was 96 years and too frail for investigation, therapy was stopped. The average blood transfusion requirement was 4 units. One individual required resuscitation with 16 units of blood, 12 of fresh frozen plasma, 4 of cryoprecipitate and 1 pool of platelets. Average length of admission was 8.4 days. <h3>Conclusion</h3> Existing data suggests that the GI bleed rate whilst on warfarin ranges from 1.3–2.6%, compared to a rate of 2.3–3.6% in association with NOACs. In our series there was an overall GI bleed rate of 3%, with 1.8% that could be considered to be significant, requiring blood products and cessation of anticoagulation. Should NOACs become more widely used the lack of established reversal techniques will require local GI units to provide a prompt and skilled bleed service. <h3>Disclosure of Interest</h3> None Declared.
TRIAL OF AN ATTENUATED BOVINE ROTAVIRUS VACCINE (RIT 4237) IN GAMBIAN INFANTS
Authors: P. Hanlon, V. Marsh, F. Shenton, O. Jobe, R. Hayes, H.C. Whittle, L. Hanlon, P. Byass, M. Hassan-King, H. Sillah, B.H. M'Boge, B.M. Greenwood
Journal: The Lancet (1987)
Impaired response to treatment with tumour necrosis factor α inhibitors in smokers with axial spondyloarthritis
Authors: Adrian Ciurea, Almut Scherer, Ulrich Weber, Pascale Exer, Jürg Bernhard, Giorgio Tamborrini, Myriam Riek, Rüdiger B Müller, Bettina Weiss, Michael J Nissen, Rudolf Kissling, Beat A Michel, Axel Finckh
Journal: Annals of the Rheumatic Diseases (2015)

Objectives To investigate the impact of smoking on the response to treatment with a first tumour necrosis factor inhibitor (TNFi) in patients with axial spondyloarthritis (axSpA) in a real-life cohort. Methods Patients fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA in the Swiss Clinical Quality Management Cohort were included in this study. The potential association between smoking status and differential response to TNFi in terms of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) was analysed using multiple adjusted longitudinal mixed effect models. Binary response rates at 1 year were assessed with multiple adjusted logistic analyses. Results A first TNFi was initiated in 698 patients with axSpA with available smoking status and a baseline or follow-up BASDAI assessment, of which 490 (70%) had complete covariate data. In comparison to non-smokers, current smokers demonstrated significantly smaller reductions in BASDAI and ASDAS scores upon treatment with TNFi (0.75 BASDAI units and 0.69 ASDAS units less, p=0.005 and 0.001, respectively) for patients with elevated baseline C-reactive protein (CRP) level. This effect was numerically smaller in patients with normal CRP. The odds for reaching a 50% improvement in BASDAI response or the ASAS criteria for 40% improvement after 1 year were significantly lower in current smokers than in non-smokers (0.54, 95% CI 0.31 to 0.95, p=0.03 and 0.43, 95% CI 0.24 to 0.76, p=0.004, respectively). Conclusions Current smoking is associated with an impaired response to TNFi in axSpA.
Genetic epidemiology of psoriasis and psoriatic arthritis
Authors: P Rahman
Journal: Annals of the Rheumatic Diseases (2005)

Psoriasis and psoriatic arthritis (PsA) are interrelated disorders, as most patients with PsA also have psoriasis. Thus it is not surprising that epidemiological and immunogenetic studies have uncovered important links between these two disorders. Both disorders are highly heritable, and the prevalence of psoriasis is 19 times higher among first degree relatives of probands with PsA compared with the general population. Multiple human leucocyte antigen (HLA) associations are shared between psoriasis and PsA, though the magnitudes of these associations differ between the diseases. Genome-wide linkage studies have noted overlapping regions of significance for these two disorders within and outside the major histocompatibility complex (MHC) region. Thus, exploration of the genetic basis of psoriasis will likely strengthen the contention of an underlying genetic susceptibility for PsA and vice versa.
The effect of verapamil on mechanical performance of acutely ischemic and reperfused myocardium in the conscious dog.
Authors: L G Sherman, C Liang, W E Boden, W B Hood
Journal: Circulation Research (1981)

The effect of verapamil, an inhibitor of transmembrane calcium flux, was studied in intact conscious dogs with myocardial ischemia produced by inflating a balloon cuff implanted on the left anterior descending coronary artery. Six dogs received a continuous infusion of verapamil (10 microgram/kg per min) beginning prior to coronary occlusion, and six received normal saline infusions. Systolic ejection shortening (SES) was measured from subendocardial ultrasonic crystals implanted in the central ischemic zone (IZ) and border zone (BZ), and in a nonischemic control zone (CZ). Hearts were paced at a constant heart rate with periodic introduction of closely coupled extrasystoles. SES was measured both for normally paced beats and during postextrasystolic potentiation (PESP). Regional myocardial blood flow was measured by injecting radioactive microspheres before, during, and after coronary occlusion. There were no significant differences between verapamil-treated dogs and saline control dogs in mean aortic pressure, heart rate, left ventricular end-diastolic pressure or dP/dt, cardiac output, or regional myocardial blood flow in IZ, BZ, or CZ. Differences in mechanical performance between two groups were noted, however. In the IZ, SES was abolished completely for normally paced beats in both groups but was significantly preserved for PESP beats in the verapamil-treated animals. In the BZ, SES was significantly reduced for normally paced beats only in the saline controls, and PESP responses were preserved to a significantly greater degree in the verapamil-treated animals. These results indicate that verapamil pretreatment exerts beneficial effects upon mechanical performance of ischemic myocardium. Since no changes in systemic hemodynamics or regional myocardial blood flow were observed, the effect may be due to the calcium-antagonistic properties of the agent.
Noninvasive Electroanatomic Mapping of Human Ventricular Arrhythmias with Electrocardiographic Imaging
Authors: Yong Wang, Phillip S. Cuculich, Junjie Zhang, Kavit A. Desouza, Ramya Vijayakumar, Jane Chen, Mitchell N. Faddis, Bruce D. Lindsay, Timothy W. Smith, Yoram Rudy
Journal: Science Translational Medicine (2011)

The rapid heartbeat of ventricular tachycardia (VT) can lead to sudden cardiac death and is a major health issue worldwide. Efforts to identify patients at risk, determine mechanisms of VT, and effectively prevent and treat VT through a mechanism-based approach would all be facilitated by continuous, noninvasive imaging of the arrhythmia over the entire heart. Here, we present noninvasive real-time images of human ventricular arrhythmias using electrocardiographic imaging (ECGI). Our results reveal diverse activation patterns, mechanisms, and sites of initiation of human VT. The spatial resolution of ECGI is superior to that of the routinely used 12-lead electrocardiogram, which provides only global information, and ECGI has distinct advantages over the currently used method of mapping with invasive catheter-applied electrodes. The spatial resolution of this method and its ability to image electrical activation sequences over the entire ventricular surfaces in a single heartbeat allowed us to determine VT initiation sites and continuation pathways, as well as VT relationships to ventricular substrates, including anatomical scars and abnormal electrophysiological substrate. Thus, ECGI can map the VT activation sequence and identify the location and depth of VT origin in individual patients, allowing personalized treatment of patients with ventricular arrhythmias.
The Myocardial Na <sup>+</sup> -H <sup>+</sup> Exchange
Authors: Morris Karmazyn, Xiaohong Tracey Gan, Rachael A Humphreys, Hiroyuki Yoshida, Keiji Kusumoto
Journal: Circulation Research (1999)

The Na(+)-H(+) exchange (NHE) is a major mechanism by which the heart adapts to intracellular acidosis during ischemia and recovers from the acidosis after reperfusion. There are at least 6 NHE isoforms thus far identified with the NHE1 subtype representing the major one found in the mammalian myocardium. This 110-kDa glycoprotein extrudes protons concomitantly with Na(+) influx in a 1:1 stoichiometric relationship rendering the process electroneutral, and its activity is regulated by numerous factors, including phosphorylation-dependent processes. There is convincing evidence that NHE mediates tissue injury during ischemia and reperfusion, which probably reflects the fact that under conditions of tissue stress, including ischemia, Na(+)-K(+) ATPase is inhibited, thereby limiting Na(+) extrusion, resulting in an elevation in [Na(+)](i). The latter effect, in turn, will increase [Ca(2+)](i) via Na(+)-Ca(2+) exchange. In addition, NHE1 mRNA expression is elevated in response to injury, which may further contribute to the deleterious consequence of pathological insult. Extensive studies using NHE inhibitors have consistently shown protective effects against ischemic and reperfusion injury in a large variety of experimental models and has led to clinical evaluation of NHE inhibition in patients with coronary artery disease. Emerging evidence also implicates NHE1 in other cardiac disease states, and the exchanger may be particularly critical to postinfarction remodeling responses resulting in development of hypertrophy and heart failure.