tbuckley/cabot-search huggingface dataset:
Modern Medical Treatment
Authors: M. Arnott
Journal: BMJ (1975)

This publication provides an excellent oppor- tunity for keeping up to date with the growing points of gastroenterology, particularly those which are of special interest and concern to the clinician.The book has been published in record time, following the course held in Oxford in January this year.It is a book which is equally important for senior gastroenterologists as it is for those who are starting to work in this field.P. R. Salmon discusses the scope of present- day gastrointestinal endoscopy.Denis Gibbs surveys the normal appearances in upper gastrointestinal endoscopy-of particular in- terest to the younger endoscopists-and K. F. R. Schiller reviews the diagnostic applications.The endoscopist, the histo- pathologist, the cytologist come together in the chapter by Martin Roca, R. Whitehead, and M. M. Boddington to review tissue diagnosis.P. B. Cotton is the obvious choice
Myeloid Suppressor Cells Regulate the Lung Environment—Letter
Authors: Momir Bosiljcic, Melisa J. Hamilton, Judit P. Banath, Nancy E. LePard, Denise C. McDougal, Jessica X. Jia, Gerald Krystal, Kevin L. Bennewith
Journal: Cancer Research (2011)

4T1 murine mammary carcinoma cells implanted in syngeneic Balb/c mice are increasingly being used in metastasis research, with some groups using this model to study tumor-induced accumulation of bone marrow-derived cells in metastatic target organs. Bone marrow-derived cells (including CD11b(+)Gr-1(+) myelomonocytic cells) are thought to modify the local lung microenvironment to facilitate subsequent colonization by metastatic tumor cells. While quantification of metastatic 4T1 tumor cells in various tissues can be done using ex vivo colony-forming assays, detection of metastatic 4T1 cells is often facilitated by expressing fluorescent proteins in the tumor cells prior to implantation. We found that Balb/c mice mount a potent immune response against 4T1 cells expressing green fluorescent protein (GFP) that includes the generation of anti-GFP antibodies in the circulation. Importantly, the number of bone marrow-derived CD11b(+)Gr-1(+) cells and metastatic tumor cells that accumulate in the lungs is significantly decreased in mice implanted with 4T1 cells expressing GFP compared with mice bearing wild-type 4T1 tumors. Taken together, our data caution against the use of GFP-expressing tumor cells in the Balb/c mouse strain, particularly for studying the influence of immunomodulatory cells on tumor cell metastasis.
Palliative Care: If It Makes a Difference, Why Wait?
Authors: Barbara Gomes
Journal: Journal of Clinical Oncology (2015)

With prognostic indicators at hand, toss a coin. Half of all patients with cancer might be predicted to die as a result of the disease within 5 years. Ask yourself whether an individual patient might die within a year, and you are likely to be incorrect in your estimate. But what is certain is that you will not be able to cure everyone. Palliative care offers patients and (note) their families a comprehensivepackageofcarebyateamofprofessionalswhobecameexperts in solving the difficult and multiple symptoms and problems that usually arise in advanced stages of the disease, helping to achieve comfort and eventually a peaceful death and bereavement. The practice has matured during the last 50 years, and it can be provided together with curative treatment. There are approximately 16,000 palliativecareservicesworldwide, 1 andfast-growingresearchdemonstrates the effectiveness of interventions, most notably that of homebasedmodelsofpalliativecaretosupportpatientsintheirownhomes, which is where most would prefer to be cared for and die, with family nearby. 2 In2012,afterpublicationofstrongevidencefromaphaseIII randomized controlled trial (RCT), 3 an American Society of Clinical Oncology provisional clinical opinion recommended consideration of combined standard oncology care and palliative care early in the course of illness for any patient with metastatic cancer and/or a high symptom burden. 4 In 2014, a landmark resolution was passed unanimously at the World Health Assembly that called for all state members to strengthen palliative care as a component of integrated treatment within the continuum of care. 5 The question of when to
Clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia
Authors: K-H Lee, J-H Lee, S-J Choi, J-H Lee, M Seol, Y-S Lee, W-K Kim, J-S Lee, E-J Seo, S Jang, C-J Park, H-S Chi
Journal: Leukemia (2005)
Pro12Ala Polymorphism in the <i>PPARG</i> Gene Contributes to the Development of Diabetic Nephropathy in Chinese Type 2 Diabetic Patients
Authors: Emanuela Lapice, Michele Pinelli, Gabriele Riccardi, Olga Vaccaro
Journal: Diabetes Care (2010)

We read with interest the article by Liu et al. (1) showing that the Pro/Pro genotype of the peroxisome proliferator–activated receptor (PPAR)-γ2 is a significant independent predictor of the development of diabetic nephropathy in a large population of Chinese type 2 diabetic patients. The study confirms, in a different ethnic group, what has already been shown in relatively small studies conducted in Caucasian diabetic patients (i.e., a population with lower prevalence of diabetic nephropathy and higher frequency of Pro12Ala genotype than the Chinese population), although none of these studies provides a complete evaluation of renal function (2–4). We report data that confirm the association between the Pro12Ala polymorphism of PPAR-γ2 and urinary albumin excretion rate (AER) in …
Enhanced Transmural Fiber Rotation and Connexin 43 Heterogeneity Are Associated With an Increased Upper Limit of Vulnerability in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy
Authors: Crystal M. Ripplinger, Wenwen Li, Jennifer Hadley, Junjie Chen, Florence Rothenberg, Raffaella Lombardi, Samuel A. Wickline, Ali J. Marian, Igor R. Efimov
Journal: Circulation Research (2007)

Human hypertrophic cardiomyopathy, characterized by cardiac hypertrophy and myocyte disarray, is the most common cause of sudden cardiac death in the young. Hypertrophic cardiomyopathy is often caused by mutations in sarcomeric genes. We sought to determine arrhythmia propensity and underlying mechanisms contributing to arrhythmia in a transgenic (TG) rabbit model (beta-myosin heavy chain-Q403) of human hypertrophic cardiomyopathy. Langendorff-perfused hearts from TG (n=6) and wild-type (WT) rabbits (n=6) were optically mapped. The upper and lower limits of vulnerability, action potential duration (APD) restitution, and conduction velocity were measured. The transmural fiber angle shift was determined using diffusion tensor MRI. The transmural distribution of connexin 43 was quantified with immunohistochemistry. The upper limit of vulnerability was significantly increased in TG versus WT hearts (13.3+/-2.1 versus 7.4+/-2.3 V/cm; P=3.2e(-5)), whereas the lower limits of vulnerability were similar. APD restitution, conduction velocities, and anisotropy were also similar. Left ventricular transmural fiber rotation was significantly higher in TG versus WT hearts (95.6+/-10.9 degrees versus 79.2+/-7.8 degrees; P=0.039). The connexin 43 density was significantly increased in the mid-myocardium of TG hearts compared with WT (5.46+/-2.44% versus 2.68+/-0.77%; P=0.024), and similar densities were observed in the endo- and epicardium. Because a nearly 2-fold increase in upper limit of vulnerability was observed in the TG hearts without significant changes in APD restitution, conduction velocity, or the anisotropy ratio, we conclude that structural remodeling may underlie the elevated upper limit of vulnerability in human hypertrophic cardiomyopathy.
State-of-the-art: rheumatoid arthritis: Figure 1
Authors: Iain B McInnes, James R O'Dell
Journal: Annals of the Rheumatic Diseases (2010)

The understanding of the pathogenesis and optimal therapeutics for rheumatoid arthritis (RA) has advanced remarkably over the last decade. This review highlights these key advances, particularly the outcomes of genome-wide scans which have provided an increasingly robust appraisal of the complex genetics that underpin RA. Such observations are placed in pathogenetic context, particularly concerning the breach of tolerance that presages synovitis and the mechanisms that subserve chronicity. The key therapeutic strategies and treatment agents, both conventional and biological, now available to effectively manage the disease are described. Throughout the review, emphasis is placed on unanswered questions and challenges in this exciting field.
Oncogene Expression and Genetic Background Influence the Frequency of DNA Copy Number Abnormalities in Mouse Pancreatic Islet Cell Carcinomas
Authors: Jeffrey H. Hager, J. Graeme Hodgson, Jane Fridlyand, Sujatmi Hariono, Joe W. Gray, Douglas Hanahan
Journal: Cancer Research (2004)

Abstract Quantitative measurements of tumor genome composition show remarkable heterogeneity in tumors arising from the same anatomical location and/or histopathological class and stage. The factors that contribute to genomic heterogeneity are not clear, but germ-line allelic variation and timing of initiating oncogenic events are likely candidates. We investigated these factors by using array comparative genomic hybridization to measure genomic aberrations in genetically engineered mouse models of pancreatic islet cell carcinoma, in which oncogenic transformation is elicited by the SV40 T antigens expressed under the control of the rat insulin promoter (RIP-Tag). Two distinct transgenic RIP-Tag lines, and three polymorphic sublines of one, enabled us to investigate the effects of genetic background and differing age of oncogene induction. Both parameters were found to bias the spectrum of genomic copy number abnormalities. Specifically, the frequency of losing portions of chromosomes 9 and 16 was significantly modulated by genetic background, with the former being lost at highest rates in the FVB/N background and the latter being lost to greatest extent in both FVB/N and C57Bl/6 tumors compared with C3HeB/Fe tumors. The frequency of losing a region of chromosome 6 varied according to the age when tumorigenesis was initiated; loss of chromosome 6 was significantly higher when oncogene expression was first activated in adulthood. These studies illustrate the utility of transgenic animal models for investigation of factors influencing genomic heterogeneity despite the commonalty of target cell type and initiating oncogene.
Electrocardiographic Left Ventricular Hypertrophy in Type 1 Diabetes
Authors: Sara Giunti, Graziella Bruno, Massimo Veglio, Gabriella Gruden, David J. Webb, Shona Livingstone, Nish Chaturvedi, John H. Fuller, Paolo Cavallo Perin
Journal: Diabetes Care (2005)

In the general population, left ventricular hypertrophy (LVH), either defined by echocardiographic or electrocardiogram (ECG) criteria, is strongly predictive of cardiovascular events, independent of conventional risk factors (1–3).

Normotensive type 1 diabetic patients with nephropathy have an increase in left ventricular mass independent of blood pressure (4) and a decrease in diastolic function (5). In the general population, LVH causes electrical heterogeneity in the heart (6) and is associated with sudden cardiac death secondary to ventricular arrhythmias. Both QT interval duration (QTc) and dispersion (QTd) are affected by electrical heterogeneity and associated with sudden death (7).

The EURODIAB IDDM Complications Study is a cross-sectional clinic-based study of diabetes complications recruiting 3,250 type 1 European diabetic subjects (8) using standardized methods of data collection. We aimed to assess ECG-LVH prevalence and association with coronary heart disease (CHD), microvascular complications, QTc, and QTd in this large cohort.

Details of the subjects and the procedures of the EURODIAB study have been published elsewhere (8–13). To assess the role of insulin resistance, an estimated glucose disposal rate (GDR) was calculated as previously described (14). Metabolic syndrome was defined according to World Health Organization guidelines (15).

LVH was defined by ECG Cornell voltage-duration product [(RaVL + SV3) × QRS complex duration] >2,623 mm × ms in …
<i>MGMT</i>Gene Silencing and Benefit from Temozolomide in Glioblastoma
Authors: Monika E. Hegi, Annie-Claire Diserens, Thierry Gorlia, Marie-France Hamou, Nicolas de Tribolet, Michael Weller, Johan M. Kros, Johannes A. Hainfellner, Warren Mason, Luigi Mariani, Jacoline E.C. Bromberg, Peter Hau, René O. Mirimanoff, J. Gregory Cairncross, Robert C. Janzer, Roger Stupp
Journal: New England Journal of Medicine (2005)

Epigenetic silencing of the MGMT (O6-methylguanine–DNA methyltransferase) DNA-repair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents.
STUDIES ON MEASLES
Authors: Francis G. Blake, James D. Trask
Journal: The Journal of Experimental Medicine (1921)

The symptomatology of the reaction induced in monkeys by inoculation with material containing the virus of measles is described. The symptoms and course of this reaction closely parallel those of human measles. The microscopic pathology of the lesions of the skin and buccal mucous membrane of monkeys experimentally infected with the virus of measles is also described. These lesions are essentially identical with the corresponding lesions of measles in man.
Nitric oxide-dependent and independent effects on human platelets treated with peroxynitrite
Authors: A Brown
Journal: Cardiovascular Research (1998)

Objective: Peroxynitrite (ONOO−) is an oxidant formed from the rapid reaction of superoxide and nitric oxide (NO) at sites of inflammation. The literature reports conflicting data on the effects of ONOO− in biological systems, with both NO- and oxidant-dependent effects having been demonstrated. The aim of this study was to investigate these distinct mechanisms through examining molecular aspects of the effects of ONOO− on human platelets, a system in which we have previously shown that ONOO− has both pro- and anti-aggregatory effects. Methods: Platelet function was assessed by measuring platelet P-selectin expression flow cytometrically, intraplatelet Ca2+ concentrations, and by light aggregometry. A colorimetric method was used to measure extracellular platelet membrane thiols. The contribution of NO and cGMP to the pharmacological effects of ONOO− was investigated using an inhibitor of the soluble guanylate cyclase (sGC), 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ), and the NO scavenger oxy-haemoglobin. Results: Peroxynitrite (50–400 μM) caused a concentration-dependent increase in the number of platelets expressing P-selectin, an increase in intraplatelet Ca2+ concentrations and a decrease in platelet membrane thiols. Peroxynitrite-induced P-selectin expression was augmented by ODQ. In contrast, when P-selectin expression was elicited by collagen, ONOO− acted as an inhibitor of this process, an effect that was further enhanced by the addition of 1% plasma. ODQ or oxy-haemoglobin abolished this inhibitory effect. Finally, low concentrations (50–100 μM) of ONOO− inhibited collagen-induced platelet aggregation, an effect that was reversed by oxy-haemoglobin. Conclusions: Peroxynitrite exerts dual effects on platelets, which are either activating or inhibitory due to the conversion of ONOO− to NO or NO donors. Peroxynitrite-induced platelet activation seems to be due to thiol oxidation and an increase in intracellular Ca2+. It is important to note that inhibitory, NO-dependent effects occur at lower concentrations than the activating effects. These data are then consistent with the conflicting literature, showing both damaging and cytoprotective effects of ONOO− in biological systems. We hypothesize that the conversion of ONOO− to NO is the critical factor determining the outcome of ONOO− exposure in vivo.
Sex differences in injury during top-level international athletics championships: surveillance data from 14 championships between 2007 and 2014
Authors: Pascal Edouard, Nina Feddermann-Demont, Juan Manuel Alonso, Pedro Branco, Astrid Junge
Journal: British Journal of Sports Medicine (2015)

Injury incidence has been reported for international athletics championships from 2007 to 2012. However, it is unclear whether male or female athletes differ in risk and/or characteristics of injuries.To compare the incidences and characteristics of injuries that occurred during international athletics championships between female and male athletes.The national medical team and the local organising committee physicians reported all injuries daily on a standardised injury report form during 14 international championships from 2007 to 2014. Relative risks (RR) of injury, 95% CI and magnitude thresholds were calculated.The rate of injuries per 1000 registered athletes was significantly higher in male (110.3±6.8) than in female (88.5±6.7) athletes (RR=1.25; 95% CI 1.13 to 1.37, small effect size). Male athletes incurred significantly more injuries in the thigh (RR=1.64; 95% CI 1.32 to 2.05, small), lower leg (RR=1.36; 95% CI 1.05 to 1.75, small) and hip/groin injuries (RR=2.26; 95% CI 1.31 to 3.88, moderate), more muscle strains (RR=1.64; 95% CI 1.33 to 2.04, small), cramps (RR=1.81; 95% CI 1.35 to 2.43, small), and especially more thigh strains (RR=1.66; 95% CI 1.25 to 2.19, small), but fewer stress fractures (RR=0.32; 95% CI 0.12 to 0.81, moderate) than female athletes. A higher injury risk of male than of female athletes was observed in sprints (RR=1.32; 95% CI 1.06 to 1.66, small), middle distance runs (RR=1.48; 95% CI 1.06 to 2.06, small), race walks (RR=2.55; 95% CI 1.27 to 5.10, moderate) and jumps (RR=2.13; 95% CI 1.53 to 2.97, moderate). No sex difference was found for cause and severity of injury.Injury risk during international athletics championships differed between female and male athletes for location, type and event groups. Injury prevention strategies should be sex-specific, regarding the differences in injury location and type.
Role of the Apolipoprotein B–Apolipoprotein A-I Ratio in Cardiovascular Risk Assessment: A Case–Control Analysis in EPIC-Norfolk
Authors: Wim A. van der Steeg, S. Matthijs Boekholdt, Evan A. Stein, Karim El-Harchaoui, Erik S.G. Stroes, Manjinder S. Sandhu, Nicholas J. Wareham, J. Wouter Jukema, Robert Luben, Aeilko H. Zwinderman, John J.P. Kastelein, Kay-Tee Khaw
Journal: Annals of Internal Medicine (2007)

Background: An elevated apolipoprotein B–apolipoprotein A-I (apo B–apo A-I) ratio is a risk factor for future coronary artery disease (CAD). It is not known whether this ratio is better than traditional lipid values for risk assessment and prediction and whether it adds predictive value to the Framingham risk score. Objective: To evaluate whether the apo B–apo A-I ratio is associated with future CAD events independent of traditional lipid measurements and the Framingham risk score and to evaluate the ability of this ratio to predict occurrence of future CAD. Design: Prospective, nested case–control study. Setting: Norfolk, United Kingdom. Participants: Apparently healthy men and women (45 to 79 years of age) in the European Prospective Investigation into Cancer and Nutrition-Norfolk. Cases (n = 869) were persons who developed fatal or nonfatal CAD. Controls (n = 1511) were persons without CAD who were matched for age, sex, and enrollment period. Measurements: Total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein, and C-reactive protein levels were measured directly. Low-density lipoprotein (LDL) cholesterol values were calculated by using the Friedewald formula. Results: The apo B–apo A-I ratio was associated with future CAD events, independent of traditional lipid values (adjusted odds ratio, 1.85 [95% CI, 1.15 to 2.98]), including the total cholesterol–HDL cholesterol ratio, and independent of the Framingham risk score (adjusted odds ratio, 1.77 [CI, 1.31 to 2.39]). However, it did no better than lipid values at discriminating between CAD cases and controls (area under the receiver-operating characteristic curve, 0.670 for total cholesterol–HDL cholesterol ratio vs. 0.673 for apo B–apo A-I ratio [P = 0.38]) and added little to the predictive value of the Framingham risk score (area under the receiver-operating characteristic curve, 0.594 for Framingham risk score alone vs. 0.613 for Framingham risk score plus apo B–apo A-I ratio [P < 0.001]). In addition, it incorrectly classified 41.1% of cases and 50.4% of controls. Limitations: No participant was taking lipid-lowering medication, and diabetes was uncommon. Conclusions: The apo B–apo A-I ratio is independently associated with, but adds little to, existing measures for CAD risk assessment and discrimination in the general population. Other characteristics of the test, such as the ability to perform it on nonfasting samples, may still make it useful in some settings.
Antibiotics in RSV bronchiolitis: still no evidence of effect
Authors: M. C. J. Kneyber, J. L. L. Kimpen
Journal: European Respiratory Journal (2007)

Antibiotics in RSV bronchiolitis: still no evidence of effectTo the Editors:Avoiding unjustified antibiotic use is of paramount importance in order to decrease worldwide development of resistance.In this context, the study by TAHAN et al. [1], which reports the results of a randomised, double-blind, placebo-controlled trial comparing clarithromycin 15 mg?kg -1 ?day -1 for 3 weeks with placebo in infants with respiratory syncytial virus (RSV) bronchiolitis, is disturbing.Careful analysis of the study shows important methodological flaws, making the results unreliable and the recommendations premature.
Nitrite Infusions to Prevent Delayed Cerebral Vasospasm in a Primate Model of Subarachnoid Hemorrhage
Authors: Ryszard M. Pluta
Journal: JAMA (2005)

Delayed cerebral vasospasm causes permanent neurological deficits or death in at least 15% of patients following otherwise successful treatment for ruptured intracranial aneurysm. Decreased bioavailability of nitric oxide has been associated with the development of cerebral vasospasm.To determine whether infusions of nitrite will prevent delayed cerebral vasospasm.A total of 14 anesthetized cynomolgus monkeys had an autologous blood clot placed around the right middle cerebral artery. Cerebral arteriography was performed before clot placement and on days 7 and 14 to assess vasospasm. The study was conducted from August 2003 to February 2004.A 90-mg sodium nitrite intravenous solution infused over 24 hours plus a 45-mg sodium nitrite bolus daily (n = 3); a 180-mg sodium nitrite intravenous solution infused over 24 hours (n = 3); or a control saline solution infusion (n = 8). Each was infused continuously for 14 days.Nitrite, S-nitrosothiol, and methemoglobin levels in blood and cerebrospinal fluid and degree of arteriographic vasospasm.In control monkeys, mean (SD) cerebrospinal fluid nitrite levels decreased from 3.1 (1.5) micromol/L to 0.4 (0.1) micromol/L at day 7 and to 0.4 (0.4) micromol/L at day 14 (P = .03). All 8 control monkeys developed significant vasospasm of the right middle cerebral artery, which was complicated by stroke and death in 1 animal. Sodium nitrite infusions increased the nitrite and methemoglobin levels (<2.1% of total hemoglobin) in the blood and cerebrospinal fluid without evoking systemic hypotension. Nitrite infusion prevented development of vasospasm (no animals developed significant vasospasm; mean [SD] reduction in right middle cerebral artery area on day 7 after subarachnoid hemorrhage of 8% [9%] in nitrite-treated monkeys vs 47% [5%] in saline-treated controls; P<.001). There was a negative correlation between the concentration of nitrite in cerebrospinal fluid and the degree of cerebral vasospasm (P<.001). Pharmacological effects of nitrite infusion were also associated with the formation of S-nitrosothiol in cerebrospinal fluid. There was no clinical or pathological evidence of nitrite toxicity.Subacute sodium nitrite infusions prevented delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage.