tbuckley/cabot-search huggingface dataset:
Nasal Polyp–Derived Superoxide Anion
Authors: MERITXELL PASTO, ELIE SERRANO, EMANUELLE UROCOSTE, MARIE-ALINE BARBACANNE, ANNIE GUISSANI, ALAIN DIDIER, MARIE-BERNADETTE DELISLE, JACQUES RAMI, JEAN-FRANÇOIS ARNAL
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The epithelium of the paranasal sinuses produces nitric oxide (NO), which probably plays a major role in the nonspecific defense of these cavities through its bacteriostatic and cilia motility stimulation properties. Abundant eosinophils of nasal polyps potentially generate superoxide anion (O2 −·), but NO and O2 −· inactivate reciprocally. The purpose of the present work was to evaluate the relationship between NO concentrations and nasal polyp production of O2 −·. Polyp fragments from 24 patients were studied using histological examination and lucigenin-enhanced chemiluminescence (to assess O2 −· production). The effect of various concentrations of exogenous NO on chemiluminescent signals was assessed. Basal and phorbol ester-stimulated O2 −· production varied largely among patients, but both were highly related to eosinophilic infiltration. A slow releasing NO donor DETA NONOate (DETA/NO NOC-18) dose dependently inhibited lucigenin-enhanced chemiluminescence from phorbol ester-stimulated polyp fragments, with an EC50 of 1.5 mM. The NO concentration in normal maxillary sinus was estimated about 10 ppm (i.e., 0.5 μ M in aqueous phase) (Lundberg, et al. Nature Med 1995;1:370). Calculations revealed that the DETA NONOate 0.75 mM and 1.5 mM generate steady-state concentrations of NO of 0.5 μ M and 2.5 μ M, respectively. In conclusion, the NO concentration present in paranasal sinuses appears to partially suppress (approximately 20–40%) O2 −· production from polyp eosinophils. Conversely, phagocytic-derived O2 −· could contribute to decrease sinus NO concentration, further altering this natural local defense. Together, these events could participate in chronic inflammation and contribute to the pathophysiology of nasal polyps.
Improvement of the practice of medicine
Authors: Jeremy Hugh Baron
Journal: BMJ (2004)

Wald's description of his encounter with the new research ethics committee forms provides a graphic illustration of the frustration and bemusement of most researchers when faced with the hurdles that must now be surmounted to conduct a clinical trial. 1 As well as the expansion in the volume of paperwork, the need to understand and comply with the regulatory requirements for good clinical practice, reporting of adverse events, and the supply and labelling of trial drugs make it almost impossible for a clinician to undertake a clinical trial without support.This is not necessarily a bad thing if it leads to better quality studies that are safer for patients, but training and support must be funded and provided if clinical trials in the public interest are to continue.Wald was unfortunate to be initiating a clinical trial in the transitional period before all the systems to implement the new clinical trials regulations were in place. 2 He therefore had to deal with old and new elements and did not benefit from the harmonised competent authority and ethics committee application.Some of the questions he found particularly irritating, because of their apparent irrelevance to ethics, are part of that common data set.Neither the Central Office for Research Ethics Committees nor the Medicines and Healthcare Products Regulatory Agency should be blamed for the content of the forms, most of which is specified in European Commission guidance 3 or the regulations themselves.The exception was Part D of the COREC application (for NHS trust approval), which has since been dropped.However, trust approval is still required and currently each trust has its own application process.For researchers who undertake multisite studies, a single form that does not duplicate information supplied elsewhere would be a boon.
Single Left Coronary Artery with Fistula to Right Ventricle
Authors: GRADY L. HALLMAN, DENTON A. COOLEY, DAN G. MCNAMARA, JOSEPH R. LATSON
Journal: Circulation (1965)

The case of an 8-year-old girl with a single coronary artery is presented. This vessel arose as a left coronary artery and followed the distribution of one coronary artery. The long circumflex branch traveled in the atrioventricular groove and continued as a vessel occupying the position usually held by the right coronary artery. It ended as a fistula to the outflow tract of the right ventricle. A continuous murmur was present clinically. Cardiac catheterization and selective angiocardiography demonstrated the anatomy of the lesion and the presence of a left-to-right shunt. Operation consisted of ligation of the fistula and anastomosis of the right ventricular portion of the coronary artery to the aorta with a Dacron tube graft. This latter maneuver established a dual inflow into the coronary arterial system and should overcome the disadvantage of a single coronary artery in the event that arteriosclerotic occlusive lesions develop in later life. Furthermore, the procedure demonstrated the feasibility of grafting technics that may find application in the treatment of anomalous origin of a coronary artery from the pulmonary artery.
TCT-474 Paclitaxel-eluting Balloon In Primary Percutaneous Coronary Intervention In Amsterdam (PAPPA): Sustained Safety And Efficacy At 12 Months Follow-up
Authors: Nicola Vos, Maurits Dirksen, Ferdinand Van Nooijen, Ton Slagboom, Giovanni Amoroso, Ferdinand Kiemeneij, Mark Patterson, Jean-Paul Herrman, René Van der Schaaf
Journal: Journal of the American College of Cardiology (2012)
Assessment of lymphokine-activated killer activity and γ-interferon production in patients with small hepatocellular carcinomas
Authors: Toshiji Saibara, Takashi Maeda, Masako Miyazaki, Saburo Onishi, Yasutake Yamamoto
Journal: Hepatology (1993)

We have previously reported depressed gamma-interferon production and depressed lymphokine-activated killer and natural killer activity in patients with relatively large hepatocellular carcinomas. These parameters were normal in cirrhosis. Some evidence had suggested a gamma-interferon production defect as the main cause of depressed lymphokine-activated killer activity in hepatocellular carcinoma, (i.e., gamma-interferon enhances lymphokine-activated killer and natural killer activity and gamma-interferon antibody inhibits lymphokine-activated killer induction). However, we were unable to clinically define the precise mechanism operating here because gamma-interferon production and lymphokine-activated killer activity were both defective in advanced hepatocellular carcinoma. In recent years, it has become possible to detect even small hepatocellular carcinomas on ultrasonography and to confirm them by fine-needle biopsy. In this study, we assessed those immune parameters in 48 patients with hepatocellular carcinomas less than 2 cm in diameter to confirm depressed immune function and to clarify the mechanism of these defects. Lymphokine-activated killer activity was defective in 31 patients (64.6%), whereas gamma-interferon production was defective in only 1 of these patients (2.1%). This observation argues against the hypothesis that defective gamma-interferon production is the primary defect and provides new insight into the mechanism of progression of defective immune function in hepatocellular carcinoma. Thirty-one of the 48 hepatocellular carcinoma patients were treated surgically, and these immune parameters were followed for 6 mo. The recovery of lymphokine-activated killer activity in all hepatocellular carcinoma patients with low lymphokine-activated killer activity suggests the tumor burden as the cause of defective lymphokine-activated killer activity.
Value of radiological follow up of childhood pneumonia.
Authors: N A Gibson, A S Hollman, J Y Paton
Journal: BMJ (1993)

<h3>Introduction:</h3> Previously we suggested that the <i>CHRNA7</i> polymorphism in nicotinic receptor genes, in particular the D15S1360 in <i>CHRNA7</i>, is associated with smoking in schizophrenia. Schizophrenia patients are usually heavy smokers. In this study we hypothesized that high-affinity nicotinic receptors are associated with smoking in such patients. <h3>Objective:</h3> To investigate the role of α4 (Ch 20) and β2 (Ch 1) genes in conferring a risk for smoking and for smoking a large number of cigarettes daily in subjects with schizophrenia. <h3>Methods:</h3> Our study sample consisted of 241 white European schizophrenia patients (157 smokers and 84 nonsmokers) from the Toronto area. Current smoking status was assessed by the medical history. We investigated 4 markers located in the <i>CHRNA4</i> gene and 3 markers located in the <i>CHRNB2</i> gene. <h3>Results:</h3> There was no difference in age or ethnicity between the 2 groups and the population was not stratified (λ = 0.4527). We found a significant association between the <i>CHRNA4</i> rs3746372 allele 1 and a large number of cigarettes smoked daily (<i>p</i> = 0.0203). The intragenic interaction between rs3787116 and rs3746372 (<i>p</i> = 0.0050) in <i>CHRNA4</i> showed a significant interaction for the number of cigarettes smoked. <h3>Conclusion:</h3> Although our findings suggest an association between rs3746372 allele 1 and heavy smoking, further study is warranted to investigate the relation between smoking and high-affinity nicotinic receptor genes in schizophrenia.
Cyclic AMP suppresses the inhibition of glycolysis by alternative oxidizable substrates in the heart.
Authors: C Depre, S Ponchaut, J Deprez, L Maisin, L Hue
Journal: Journal of Clinical Investigation (1998)

In normoxic conditions, myocardial glucose utilization is inhibited when alternative oxidizable substrates are available. In this work we show that this inhibition is relieved in the presence of cAMP, and we studied the mechanism of this effect. Working rat hearts were perfused with 5.5 mM glucose alone (controls) or together with 5 mM lactate, 5 mM beta-hydroxybutyrate, or 1 mM palmitate. The effects of 0.1 mM chlorophenylthio-cAMP (CPT-cAMP), a cAMP analogue, were studied in each group. Glucose uptake, flux through 6-phosphofructo-1-kinase, and pyruvate dehydrogenase activity were inhibited in hearts perfused with alternative substrates, and addition of CPT-cAMP completely relieved the inhibition. The mechanism by which CPT-cAMP induced a preferential utilization of glucose was related to an increased glucose uptake and glycolysis, and to an activation of phosphorylase, pyruvate dehydrogenase, and 6-phosphofructo-2-kinase, the enzyme responsible for the synthesis of fructose 2,6-bisphosphate, the well-known stimulator of 6-phosphofructo-1-kinase. In vitro phosphorylation of 6-phosphofructo-2-kinase by cAMP-dependent protein kinase increased the Vmax of the enzyme and decreased its sensitivity to the inhibitor citrate. Therefore, in hearts perfused with various oxidizable substrates, cAMP induces a preferential utilization of glucose by a concerted stimulation of glucose transport, glycolysis, glycogen breakdown, and glucose oxidation.
Population-Based Molecular Prognosis of Breast Cancer by Transcriptional Profiling
Authors: Yan Ma, Yong Qian, Liang Wei, Jame Abraham, Xianglin Shi, Vincent Castranova, E. James Harner, Daniel C. Flynn, Lan Guo
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The purpose of this study is to predict breast cancer recurrence and metastases and to identify gene signatures indicative of clinicopathologic characteristics using gene expression patterns derived from cDNA microarray. Experimental Design: Expression profiles of 7,650 genes were investigated on an unselected group of 99 node-negative and node-positive breast cancer patients to identify prognostic gene signature of recurrence and metastases. The identified gene signature was validated on independent 78 patients with primary invasive carcinoma (T1/T2 and N0) and on 58 patients with locally advanced breast cancer (T3/T4 and/or N2). The gene predictors were identified using a combination of random forests and linear discriminant analysis function. Results: This study identified a new 28-gene signature that achieved highly accurate disease-free survival and overall survival (both at P &amp;lt; 0.001, time-dependent receiver operating characteristic analysis) in individual breast cancer patients. Patients categorized into high-risk, intermediate-risk, and low-risk groups had distinct disease-free survival (P &amp;lt; 0.005, Kaplan-Meier analysis, log-rank test) in three patient cohorts. A strong association (P &amp;lt; 0.05) was identified between risk groups and tumor size, tumor grade, estrogen receptor and progesterone receptor status, and HER2/neu overexpression in the studied cohorts. We also identified 14-gene predictors of nodal status and 9-gene predictors of tumor grade. Conclusions: This study has established a population-based approach to predicting breast cancer outcomes at the individual level exclusively based on gene expression patterns. The 28-gene recurrence signature has been validated as quantifying the probability of recurrence and metastases in patients with heterogeneous histology and disease stage.
Mucocutaneous Lymph Node Syndrome
Authors: Paul S. Bergeson
Journal: JAMA (1977)

Mucocutaneous lymph node syndrome is a recently described entity whose principal signs and symptoms include fever, unresponsiveness to antibiotics, congested conjunctivae, reddening of the oral cavity, lips, palms, and soles, exanthem, edema, nonsuppurative cervical adenitis, and desquamation of the fingertips. Almost 7,000 cases have been reported in Japan. Analysis of the 39 cases reported in the United States reveals findings similar to those in Japan. United States cases, however, have had a higher boyto-girl ratio (2:1), and age distribution peaks at a later time (3 years of age). We report a case with many characteristics of Rocky Mountain spotted fever, including a positive Weil-Felix reaction. Some cases of mucocutaneous lymph node syndrome may be misdiagnosed as Rocky Mountain spotted fever. (<i>JAMA</i>237:2299-2302, 1977)
Immunization with a novel human apo B100 related peptide reduces atherosclerosis and inflammation in apo E null mice
Authors: Odette S. Reyes, Kuang-Yuh Chyu, Juliana Yano, Xioaning Zhao, Bojan Cercek, Sanjay Kaul, Jan Nilsson, Prediman K. Shah
Journal: Journal of the American College of Cardiology (2002)
Is excessive running predictive of degenerative hip disease? Controlled study of former elite athletes.
Authors: B. Marti, M. Knobloch, A. Tschopp, A. Jucker, H. Howald
Journal: BMJ (1989)

OBJECTIVE--To determine the effects of regular long distance running on the state of the hips in later life. DESIGN--Retrospective study of a cohort of elite athletes and a group of normal, healthy, untrained controls examined 15 years after initial testing. SETTING--Research project at school for physical education and sports. SUBJECTS--27 Former long distance runners (mean age 42), nine former bobsleigh riders (mean age 42), and 23 normal, healthy, untrained men (mean age 35) who had been examined in 1973 and who agreed to re-examination in 1988. MAIN OUTCOME MEASURE--Radiological evidence of degenerative hip disease in 1988. RESULTS--Physiological and exercise characteristics of all subjects had been recorded in 1973, and in 1988 these measurements were repeated together with radiological examination of the hips. An additive radiological index of hip disease based on grades of subchondral sclerosis, osteophyte formation, and joint space narrowing was significantly increased among runners as compared with bobsleigh riders and untrained controls. After adjustment for age the significant effect of type of sports activity remained (p = 0.032). In multivariate analyses age and milage run in 1973 (97 km/week) emerged as independent, significant, and positive predictors of radiological signs of degenerative hip disease in 1988 (p = 0.017 and p = 0.024 respectively). Among runners alone running pace in 1973 rather than milage run was the stronger predictor of subsequent degenerative hip disease. The milage run in 1988 was not particularly predictive of the radiological index, but endurance in 1988 was inversely related to degenerative hip disease seen radiologically. CONCLUSION--Long term, high intensity, high milage running should not be dismissed as a potential risk factor for premature osteoarthritis of the hip.
Studies using lectins to determine mineral interactions with cellular membranes.
Authors: B T Mossman, L Jean, J M Landesman
Journal: Environmental Health Perspectives (1983)

Chrysotile asbestos interacts with mucin-secreting cells of tracheal organ cultures, causing an increase in secretion of mucin into the culture medium. This response occurs in the absence of obvious morphologic damage to tracheal epithelial cells. We speculated that asbestos-induced hypersecretion was regulated by the interaction of fibers with specific carbohydrate residues on the cell surface. To test this hypothesis, lectins, i.e., proteins with a high affinity for mono- and oligosaccharides on the plasma membrane, were added to tissues 30 min before addition of chrysotile. Secretion of mucin into the medium was then determined over a 2-hr period by using incorporation of 3H-glucosamine. Blocking of alpha-D-mannose and alpha-D-glucose residues inhibited chrysotile-induced hypersecretion (p less than 0.05), whereas lectins blocking residues of alpha-D-N-acetylgalactosamine, beta-D-N-acetylglucosamine, alpha-L-fucose and sialic acids were ineffective. Preincubation of cultures with carboxypeptidase A or phospholipase A2, but not with neuraminidase, diminished mucin secretion caused by chrysotile. To determine if the positive surface charge of chrysotile was important in interaction with mucin cells, we examined comparatively the effects of various polycations (cationic ferritin, polylysine, DEAE-dextran) and chrysotile after leaching of fibers to remove Mg2+. Although use of polycations enhanced secretion of mucin, effects were not as striking as those observed with chrysotile. In contrast, leached chrysotile failed to elicit a hypersecretory response. These results suggest the interaction of a positively charged component (presumably Mg2+) of chrysotile with glycolipids and glycoproteins containing terminal residues of alpha-D-mannose or alpha-D-glucose.
Antibiotic use in community in Northern Ireland is a third higher than in England
Authors: R. Dobson
Journal: BMJ (2008)

Antibiotic use in the community varies widely across the four countries of the United Kingdom, with use in Northern Ireland more than a third greater than in England, a study has found.

Major differences were also found among European nations, with the level of use in France double that in England and Germany and almost triple that in Russia, says the report in the Journal of Antimicrobial Chemotherapy (doi:10.1093/jac/dkn386).

The researchers used data for 2005 from 28 …
Pseudonormal Hepatobiliary Scintigraphy in a Patient with a Bile Leak
Authors: AMOLAK SINGH, GUIDO VALLE
Journal: Clinical Nuclear Medicine (1990)

An unusual case, in which the hepatobiliary scintiscan could be mistaken for a normal study is reported. The extravasated bile in the gallbladder fossa assumed a configuration mimicking the gallbladder. Careful image scrutiny and a knowledge of recent cholecystectomy identified bile leakage. History of biliary tract surgery or penetrative abdominal trauma should alert a physician to the possibility of bile leakage. Absence of scintigraphic evidence of biliary tract obstruction and significant liver failure to account for the elevation in serum bilirubin in an appropriate setting is suggestive of bile leakage. Direct evidence of a bile leak is diagnostic.
IMPROVED OUTCOME WITH PREVENTIVE CARDIAC RESYNCHRONIZATION THERAPY IN THE ELDERLY, A MADIT-CRT SUBSTUDY
Authors: Justin Penn, Ilan Goldenberg, Arthur J. Moss, Scott McNitt, Wojciech Zareba, Helmut U. Klein, David S. Cannom, Scott D. Solomon, Along Barsheshet, David T. Huang
Journal: Journal of the American College of Cardiology (2011)
Should we treat subclinical hypothyroidism?
Authors: C. B Pham, A. F Shaughnessy
Journal: BMJ (2008)

Subclinical hypothyroidism is a laboratory definition: a raised concentration of thyroid stimulating hormone (TSH) yet a normal concentration of free thyroid hormone, without specific symptoms of thyroid dysfunction. Patients with subclinical hypothyroidism have an increased risk of progressing to overt hypothyroidism. Yet uncertainty exists as to the benefits of treating such patients.

Recent systematic reviews of cohort studies have shown a significant increase in coronary heart disease and cardiovascular related mortality in people with subclinical hypothyroidism and a TSH concentration >10 mU/l, but no difference in overall mortality.1 2 The benefits of treating subclinical hypothyroidism are also uncertain: although two systematic reviews have suggested that treatment may decrease total cholesterol and low density lipoprotein cholesterol levels, particularly in people with TSH concentrations of >10 mU/l,3 4 no research has shown a decrease in coronary heart disease or mortality with treatment.

The Clinical Evidence review reports mixed results from small …
Tumor Angiogenesis: A Possible Control Point in Tumor Growth
Authors: JUDAH FOLKMAN
Journal: Annals of Internal Medicine (1975)

The growth of solid tumors has an avascular phase and vascular phase. These discrete phases each have unique properties; a diffusible tumor angiogenesis factor seems to be responsible for initiating the vascular phase; and when the avascular phase is prolonged, solid tumors in a variety of experimental models fail to grow beyond a few millimetres. This perspective of the manner by which solid tumors grow has become a guide for further experiments to elucidate the nature of tumor angiogenesis factor, to determine whether tumor neovascularization can be inhibited, and to find out whether the neovascularization that sometimes accompanies wound healing, inflammation, or delayed hypersensitivity operates through a different mechanism than tumor angiogenesis.
Abnormal Lung Function in Adults With Congenital Heart Disease: Prevalence, Relation to Cardiac Anatomy, and Association With Survival
Authors: Rafael Alonso-Gonzalez, Francesco Borgia, Gerhard-Paul Diller, Ryo Inuzuka, Aleksander Kempny, Ana Martinez-Naharro, Oktay Tutarel, Philip Marino, Kerstin Wustmann, Menelaos Charalambides, Margarida Silva, Lorna Swan, Konstantinos Dimopoulos, Michael A. Gatzoulis
Journal: Circulation (2013)

Background— Restrictive lung defects are associated with higher mortality in patients with acquired chronic heart failure. We investigated the prevalence of abnormal lung function, its relation to severity of underlying cardiac defect, its surgical history, and its impact on outcome across the spectrum of adult congenital heart disease. Methods and Results— A total of 1188 patients with adult congenital heart disease (age, 33.1±13.1 years) undergoing lung function testing between 2000 and 2009 were included. Patients were classified according to the severity of lung dysfunction based on predicted values of forced vital capacity. Lung function was normal in 53% of patients with adult congenital heart disease, mildly impaired in 17%, and moderately to severely impaired in the remainder (30%). Moderate to severe impairment of lung function related to complexity of underlying cardiac defect, enlarged cardiothoracic ratio, previous thoracotomy/ies, body mass index, scoliosis, and diaphragm palsy. Over a median follow-up period of 6.7 years, 106 patients died. Moderate to severe impairment of lung function was an independent predictor of survival in this cohort. Patients with reduced force vital capacity of at least moderate severity had a 1.6-fold increased risk of death compared with patients with normal lung function ( P =0.04). Conclusions— A reduced forced vital capacity is prevalent in patients with adult congenital heart disease; its severity relates to the complexity of the underlying heart defect, surgical history, and scoliosis. Moderate to severe impairment of lung function is an independent predictor of mortality in contemporary patients with adult congenital heart disease.