tbuckley/cabot-search huggingface dataset:
Defining heart failure
Authors: R Coronel
Journal: Cardiovascular Research (2001)

The definition of heart failure is hampered by the wide variability of the clinical symptoms and signs, and of their etiologies. Many attempts have been made to come up with a general set of criteria that describe heart failure [1–7]. These criteria include clinical, epidemiological, pathophysiological, and exercise-related criteria and criteria derived from the patient's response to therapy. The need for a more circumscript definition reflects the hope to be able to stratify patient groups, to detect heart failure at an earlier stage and to optimally treat patients. At the basis of this need is our wish to understand heart failure as a pathogenetic entity. Moreover, to attain this purpose a clear definition is required for the design of adequate experimental protocols.

From medical history we know that the understanding of diseases often has started with the recognition of consistency in a set of symptoms and signs. The starting point for our knowledge therefore is the definition of such a set of characteristics. Here, pathophysiological and medical objectives may, however, lead to conflicts: those searching for a pathophysiologic entity may produce a common denominator of the characteristics, whereas those concerned with the optimal treatment of their patients may come up with a description that covers all possible appearances of the phenomenon. Debates between followers of the standpoint of comprehensiveness and those of brevity continue [4–7].

In order to uncover the dilemmas in the definition of heart failure, the editors of Cardiovascular Research have recently performed a survey amongst the Journal's reviewers. A letter was sent to 2238 active reviewers with a request for confirmation of data stored in the Journal's database. In the same letter the reviewers were asked to give a definition of heart failure in less than 150 words. In the 2 months following the mailing … 

*Corresponding author. Tel.: +31-20-566-3267; fax: +31-20-697-5458 r.coronel{at}amc.nl
Targeted reduction of advanced glycation improves renal function in obesity
Authors: Brooke E. Harcourt, Karly C. Sourris, Melinda T. Coughlan, Karen Z. Walker, Sonia L. Dougherty, Sofianos Andrikopoulos, Amy L. Morley, Vicki Thallas-Bonke, Vibhasha Chand, Sally A. Penfold, Maximilian P.J. de Courten, Merlin C. Thomas, Bronwyn A. Kingwell, Angelika Bierhaus, Mark E. Cooper, Barbora de Courten, Josephine M. Forbes
Journal: Kidney International (2011)
Hip Fractures and Fluoridation-Reply
Authors: Christa Danielson
Journal: JAMA (1993)

ABSTRACT In Reply. —To address the first question, we did have a lower CI on our male subjects that was equal to 1.00. Our P value was equal to.05. There is still a one in 20 chance that the data may be wrong. We chose to report our result as statistically significant: perhaps reporting the P value in this case would have been less confusing.We analyzed the data as a retrospective cohort. It is for this reason that we used RR instead of OR, as would be more commonly used in a case-control study.Again, the study was ecological in nature. The RRs were small and we did not get individual data as other risk factors for hip fracture. The results are interesting, but certainly not conclusive.
Radiotherapy for Postoperative Thoracic Lymph Node Recurrence of Non–Small-Cell Lung Cancer Provides Better Outcomes If the Disease Is Asymptomatic and a Single-Station Involvement
Authors: Jiro Okami, Kinji Nishiyama, Ayako Fujiwara, Koji Konishi, Takashi Kanou, Toshiteru Tokunaga, Teruki Teshima, Masahiko Higashiyama
Journal: Journal of Thoracic Oncology (2013)
Quantitative Assessment of Coronary Vasoreactivity in Humans In Vivo
Authors: Volker Schächinger, Andreas M. Zeiher
Journal: Circulation (1995)

Background Disturbances in vasomotor tone are closely linked to the development of atherosclerosis and play an integral part in the pathophysiology of myocardial ischemia in patients with coronary artery disease. Currently, evaluation of coronary vasomotor tone relies on assessment of luminal changes in response to vasoactive stimuli by quantitative angiography. Assessment of luminal changes, however, may be misleading because of the effects of geometric magnification induced by atherosclerotic wall thickening and differences in basal tone, which may obscure potential effects of vasoactive stimuli. Methods and Results Combining angiographic measurements of luminal changes with measurements of coronary wall architecture determined by intracoronary ultrasound, we calculated absolute coronary arterial vasomotor tone in 34 patients with angiographically normal or “minimally diseased” coronary arteries. Epicardial artery vasodilator capacity in response to intracoronary nitroglycerin decreased significantly with increasing atherosclerotic wall thickening. An inverse relation existed between local atherosclerotic plaque load and nitroglycerin-induced changes in vasomotor tone ( r =−.65, P &lt;.0001) regardless of potential systematically operative factors. At the same time, basal vasomotor tone significantly decreased with increasing local atherosclerotic wall thickening ( r =−.38, P =.004). The vasomotor effects of acetylcholine, an endothelium-dependent vasodilator, were inversely related to wall thickening only in segments with very minor degrees of atherosclerosis, whereas no such relation was observed for epicardial artery segments with more advanced atherosclerotic wall thickening. In these segments, however, vasoreactivity to acetylcholine was closely correlated with basal vasomotor tone ( r =−.62, P =.0002). Conclusions Atherosclerosis is associated with impairment of the vasodilator response to both nitroglycerin and acetylcholine in epicardial arteries in vivo. Basal vasomotor tone appears to be the primary determinant of the altered coronary vasoreactivity in response to vasoactive stimuli.
Abstract 4773: Is upregulation of CYP2R1-, CYP27B1- and CYP24 genes in clear cell renal cell carcinoma tissue involved in carcinogenesis.
Authors: Anja E. Urbschat, Patrick Paulus, Quirine Freiin von Quernheim, Patrick Brück, Elizabeth Ramos-Lopez
Journal: Cancer Research (2013)

Abstract Renal cell carcinoma (RCC) represent approximately 3-5% of all malignancies reported each year. Among these clear cell renal cell carcinoma (ccRCC) represent the most frequently diagnosed histological classification accounting for 80% of renal cell carcinoma. The incidence has been reported to be higher in countries located at higher latitudes. In this context UVB-light which is essential for the synthesis of vitamin D has been inversely associated with the development of diverse carcinomas including renal cell carcinoma. Further steps of vitamin D synthesis are performed by CYP2R1, CYP27B1 and CYP24. We therefore investigated the quantitative mRNA expression of the CYP2R1, CYP27B1 and CYP24 genes in patients (n=29) with ccRCC. For this purpose total RNA was isolated from tumor and corresponding adjacent healthy tissues of all patients and integrity was assessed on a denaturing agarose gel stained with ethidium bromide. Intact RNA was transcribed using random hexameric primers and reverse transcriptase. Reverse transcription was performed and amplified by real-time PCR. Statistic association was evaluated by Mann-Whitney-Test and Kruskal-Wallis-Test. A P value less than 0.05 was considered significant. mRNA of all three genes (CYP2R1, CYP27B1 and CYP24) was expressed in both normal and carcinoma tissue with a significant upregulation in carcinoma tissue compared to normal tissue (p&amp;lt;0.0001). In tumor tissue CYP24 displayed a significantly higher expression than CYP27B1 or CYP2R1. Furthermore CYP27B1 showed a higher expression than CYP2R1 (p&amp;lt;0.0001). No differences in the expression of CYP2R1, CYP27B1 and CYP24 were found in normal renal tissue. We therefore conclude that differing gene expression of CYP2R1, CYP27B1 and CYP24 in normal- and carcinoma tissue could be involved in the pathogenesis of renal cell carcinoma. Citation Format: Anja E. Urbschat, Patrick Paulus, Quirine Freiin von Quernheim, Patrick Brück, Elizabeth Ramos-Lopez. Is upregulation of CYP2R1-, CYP27B1- and CYP24 genes in clear cell renal cell carcinoma tissue involved in carcinogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4773. doi:10.1158/1538-7445.AM2013-4773
The photodynamic therapy on Streptococcus mutans biofilms using erythrosine and dental halogen curing unit
Authors: Young-Ho Lee, Ho-Won Park, Ju-Hyun Lee, Hyun-Woo Seo, Si-Young Lee
Journal: International Journal of Oral Science (2012)

The purpose of our study was to evaluate the effect of photodynamic therapy (PDT), using erythrosine as a photosensitizing agent and a dental halogen curing unit as a light source, on Streptococcus mutans in a biofilm phase. The S. mutans biofilms were formed in a 24-well cell culture cluster. Test groups consisted of biofilms divided into four groups: group 1: no photosensitizer or light irradiation treatment (control group); group 2: photosensitizer treatment alone; group 3: light irradiation alone; group 4: photosensitizer treatment and light irradiation. After treatments, the numbers of colony-forming unit (CFU) were counted and samples were examined by confocal laser scanning fluorescence microscopy (CLSM). Only group 4 (combined treatment) resulted in significant increases in cell death, with rates of 75% and 55% after 8 h of incubation, and 74% and 42% at 12 h, for biofilms formed in brain–heart infusion (BHI) broth supplemented with 0% or 0.1% sucrose, respectively. Therefore, PDT of S. mutans biofilms using a combination of erythrosine and a dental halogen curing unit, both widely used in dental clinics, resulted in a significant increase in cell death. The PDT effects are decreased in biofilms that form in the presence of sucrose. Protective biofilms produced by cariogenic bacteria can be treated effectively with common and inexpensive dental equipment, Korean research shows. Ho-Won Park and colleagues from Gangneung-Wonju National University have shown that, after eight hours of incubation in cell culture, a novel variation of the technique known as photodynamic therapy (PDT) kills 75% of the biofilm-producing bacterium Streptococcus mutans. In cultures containing sucrose, the treatment was less effective at 55%. PDT uses a nontoxic photosensitizer that, when exposed to light, produces reactive oxygen species that kill bacteria. Although previous research had shown that PDT is effective against cariogenic bacteria, the treatments used specialized and expensive equipment. Park and colleagues' variation of PDT uses only the photosensitizer erythrosine and a halogen curing unit, which are already used widely by dentists. Future research will investigate its efficacy in clinical situations.
Caring for the Older Person With Chronic Obstructive Pulmonary Disease
Authors: Terri R. Fried, Carlos A. Vaz Fragoso, Michael W. Rabow
Journal: JAMA (2012)

Chronic obstructive pulmonary disease (COPD), a common disease in elderly patients, is characterized by high symptom burden, health care utilization, mortality, and unmet needs of patients and caregivers. Respiratory failure and dyspnea may be exacerbated by heart failure, pulmonary embolism, and anxiety; by medication effects; and by other conditions, including deconditioning and malnutrition. Randomized controlled trials, which provide the strongest evidence for guideline recommendations, may underestimate the risk of adverse effects of interventions for older patients with COPD. The focus of guidelines on disease-modifying therapies may not address the full spectrum of patient and caregiver needs, particularly the high rates of bothersome symptoms, risk of functional and cognitive decline, and need for end-of-life care planning. Meeting the many needs of older patients with COPD and their families requires that clinicians supplement guideline-recommended care with treatment decision making that takes into account older persons' comorbid conditions, recognizes the trade-offs engendered by the increased risk of adverse events, focuses on symptom relief and function, and prepares patients and their loved ones for further declines in the patient's health and their end-of-life care. A case of COPD in an 81-year-old man hospitalized with severe dyspnea and respiratory failure highlights both the challenges in managing COPD in the elderly and the limitations in applying guidelines to geriatric patients.
Differences in Glucose Tolerance Between Fixed-Dose Antihypertensive Drug Combinations in People With Metabolic Syndrome
Authors: Kristel J. O'Malley, Marshall J. Bouldin, Daniel M. Riche
Journal: Diabetes Care (2007)

We read with great interest the recent article by Bakris et al. (1). The authors reported that in patients with impaired glucose tolerance (IGT), the combination of losartan and hydrochlorothiazide resulted in an increased rate of new-onset diabetes when compared with trandolapril and verapamil. Indeed, we agree that thiazide diuretics have a history of producing adverse metabolic effects; however, we contend that losartan is an inappropriate angiotensin receptor blocker (ARB) choice. Losartan has inadequate peroxisome proliferator–activated receptor …
ESGE/ESGENA guideline for process validation and routine testing for reprocessing endoscopes in washer-disinfectors, according to the European Standard prEN ISO 15883 parts 1, 4 and 5
Authors: U. Beilenhoff, C. Neumann, H. Biering, R. Blum, V. Schmidt, J. Rey
Journal: Endoscopy (2007)

2. Quality management: the roles of validation and routine testing3. Responsibilities and qualifications4. Validation4.1. Prerequisites4.2. Installation qualification (IQ)4.3. Operational qualification (OQ)4.4. Performance qualification (PQ)5. Routine testing6. Frequency6.1. Frequency of validation and revalidation6.2. Frequency of routine testing7. References8. AppendicesAppendix 1: GlossaryAppendix 2.: Example of a checklist of prerequisites for installation of a washer-disinfectorAppendix 3.: Example of a checklist for installation qualificationAppendix 4.: Example of a checklist for operational qualificationAppendix 5.: Example of a checklist for performance qualificationAppendix 6.: Routine testing: checklist
Small-Molecule Inhibitors of Phosphatidylinositol 3-Kinase/Akt Signaling Inhibit Wnt/β-Catenin Pathway Cross-Talk and Suppress Medulloblastoma Growth
Authors: Ninib Baryawno, Baldur Sveinbjörnsson, Staffan Eksborg, Ching-Shih Chen, Per Kogner, John Inge Johnsen
Journal: Cancer Research (2009)

Activation of the beta-catenin and receptor kinase pathways occurs often in medulloblastoma, the most common pediatric malignant brain tumor. In this study, we show that molecular cross-talk between the beta-catenin and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways is crucial to sustain medulloblastoma pathophysiology. Constitutive activation of phosphoinositide-dependent protein kinase 1 (PDK1), Akt, and phosphorylation of [corrected] glycogen synthase kinase 3beta (GSK-3beta) was detected by immunohistochemistry in all primary medulloblastomas examined (n = 41). Small-molecule inhibitors targeting the PI3K/Akt signaling pathway affected beta-catenin signaling by activation [corrected] of GSK-3beta, [corrected] resulting in cytoplasmic retention of beta-catenin and reduced expression of its target genes cyclin D1 and c-Myc. The PDK1 inhibitor OSU03012 induced mitochondrial-dependent apoptosis of medulloblastoma cells and enhanced the cytotoxic effects of chemotherapeutic drugs in a synergistic or additive manner. In vivo, OSU03012 inhibited the growth of established medulloblastoma xenograft tumors in a dose-dependent manner and augmented the antitumor effects of mammalian target of rapamycin inhibitor CCI-779. These findings demonstrate the importance of cross-talk between the PI3K/Akt and beta-catenin pathways in medulloblastoma and rationalize the PI3K/Akt signaling pathway as a therapeutic target in treatment of this disease.
Huntington's centre faces closure
Authors: C. Wallerstein
Journal: BMJ (2000)

The world's only centre for people with Huntington's disease faces closure through lack of funds less than a year after it was set up. The disease affects only 1 in 10000 people worldwide.

But in the tiny, poor, fishing villages around Lake Maracaibo in Venezuela, up to 40% of the population is at risk. At least 1000 people in the area are showing symptoms of the disease. Nearly 3000 more are presymptomatic. Symptoms usually start with slight clumsiness, developing into incontinence, depression, total inability to move or talk, and dementia.

Death is usually caused by heart failure or pneumonia. All those affected are descendants of a 19th century couple who had 20 children. There are now 16000 descendants. Those affected are often shunned by …
Health inequalities and cystic fibrosis
Authors: D. Taylor-Robinson, M. S. Schechter
Journal: BMJ (2011)

Even for genetic diseases, social conditions are still important determinants of outcome 

Cystic fibrosis is the most common serious inherited disease in white populations. Intensive support from family and healthcare services is needed from the time of diagnosis onwards, and most patients die prematurely from respiratory failure. Survival has dramatically improved over successive birth cohorts, such that British children born in the 21st century will have a median survival of over 50 years.1 However, disease progression and survival still vary greatly, mostly as a result of social and environmental, rather than genetic, determinants.2 It has been known for more than 20 years that people with cystic fibrosis from socioeconomically disadvantaged backgrounds die younger than those in more advantaged positions.3

In a linked observational study (doi:10.1136/bmj.d4662), Barr and colleagues used death registration data in England and Wales to show that this socioeconomic divide in premature mortality in cystic fibrosis has persisted with no substantial narrowing for over four decades.4 They also show that female patients continue to die at a younger age than men. What can we learn from this, and what are the implications …
ABO Blood Group IgM Isoagglutinins Interact with Tumor-Associated O-Glycan Structures in Pancreatic Cancer
Authors: Bianca T. Hofmann, Anne Stehr, Thorsten Dohrmann, Cenap Güngör, Lena Herich, Jens Hiller, Sönke Harder, Florian Ewald, Florian Gebauer, Michael Tachezy, Clarissa Precht, Jakob R. Izbicki, Maximilian Bockhorn, Christoph Wagener, Gerrit Wolters-Eisfeld
Journal: Clinical Cancer Research (2014)

The ABO gene locus is associated with the risk of developing pancreatic ductal adenocarcinoma (PDAC) resulting in an increased incidence in individuals with non-O blood groups. Up to 90% of PDAC specimens display alterations in mucin type O-GalNAc glycosylation. Because aberrant O-GalNAc glycans (Tn and T antigen) are structurally related to blood group A and B glycans, we investigated the role of IgM isoagglutinins in PDAC.Binding studies of IgM isoagglutinins toward blood group A, B, Tn antigen, and T antigen glycoconjugates from patients with PDAC and healthy individuals were conducted. Isoagglutinin titers and total IgM were compared between patients with PDAC and control group. An anti-A antibody was used for immunoprecipitation of aberrant O-glycosylated tumor proteins and subsequent mass spectromic analysis.We found that IgM isoagglutinins bind blood group antigens, Tn and T glycoconjugates as well as tumor-derived glycoproteins. Blood group A isoagglutinins exhibited a strong binding toward blood group B antigen and T antigen, whereas blood group B showed binding to blood group A antigen and Tn antigen. Furthermore, we confirmed a decreased frequency in individuals with blood group O and observed a significant decrease of IgM isoagglutinin titers in PDAC sera compared with control sera, whereas total IgM levels were unaltered. We identified new PDAC-derived O-GalNAc glycoproteins by mass spectrometry using a blood group A-specific antibody.Our data elucidated a novel interaction of blood group IgM isoagglutinins and PDAC O-GalNAc glycoproteins that may contribute to the pathogenesis and progression of pancreatic cancer.
Private healthcare market may be anti-competitive with poor returns for patients
Authors: N. Hawkes
Journal: BMJ (2012)

The Office of Fair Trading (OFT) has referred the private healthcare market to the Competition Commission, saying that it is not working properly for consumers. It warned last December that it intended to make the referral and the results of a public consultation since then have not changed its mind.

The OFT is critical of a lack of the information needed by consumers to make informed decisions and says that local monopolies and the ability of existing providers to make it difficult for new entrants to the market distort competition. As a result patients might pay higher prices than they need to or get poorer quality care.

In its market study, the OFT says that …
Principles of Pathobiology
Authors: A. E. Rodin
Journal: JAMA (1975)

This textbook is an excellent summation of the molecular, enzymatic, and ultramicroscopic changes in disease processes that demonstrate significant abnormalities at these levels. Included are chapters on cell injury, inflammation, host-parasite relationships, immunology, neoplasia, and developmental diseases. Although this is the second edition, only the chapter on cell injury appears to have been revised sufficiently to include a significant number of new references. For example, the chapter on developmental disease makes no mention of the potential of amniocentesis for prenatal diagnosis of genetic diseases. The preface states that "The book is designed for easy use by busy students." It is not, however, suitable as the major source of information for a basic pathology course. Not included are disease processes that have no significant ultrastructural changes, such as hemodynamic disturbances. Even in the extensive chapter on cell injury there is not sufficient orientation to provide the medical student with a basis
Tacrolimus and steroids versus ciclosporin microemulsion, steroids, and azathioprine in children undergoing liver transplantation: randomised European multicentre trial
Authors: Deirdre Kelly, Paloma Jara, Burkhard Rodeck, Panayotis Lykavieris, Martin Burdelski, Michael Becker, Bruno Gridelli, Olivier Boillot, Javier Manzanares, Raymond Reding
Journal: The Lancet (2004)