tbuckley/cabot-search huggingface dataset:
Immunological significance of cytotoxic T lymphocyte epitope variants in patients chronically infected by the hepatitis C virus.
Authors: K M Chang, B Rehermann, J G McHutchison, C Pasquinelli, S Southwood, A Sette, F V Chisari
Journal: Journal of Clinical Investigation (1997)

This study was performed to test the hypothesis that cytotoxic T lymphocyte (CTL) selection of hepatitis C virus (HCV) escape variants plays a role in HCV persistence. The peripheral blood CTL responsiveness of patients with well-established chronic hepatitis C to a panel of 10 prototype HCV peptides (genotype 1a) was compared with the corresponding sequences encoded by the infecting viruses in each patient. Variant viral peptide sequences were threefold more frequent in the presence of a CTL response than in its absence, and CTL responses were detected nearly twice as often in association with variant rather than with prototype viral peptide sequences. Furthermore, over half of the patients were infected with potential CTL escape variants that contained nonimmunogenic and noncross-reactive variant peptides many of which displayed reduced HLA-binding affinity. Surprisingly, follow up analysis over a period of up to 46 mo revealed that, in contrast to the relatively high frequency of escape variants initially observed, the subsequent emergence rate of CTL escape variants was very low. Interestingly, the one escape variant that was detected proved to be a CTL antagonist. Collectively, these observations suggest that CTL selection of epitope variants may have occurred in these patients before their entrance into the study and that it may have played a role in HCV persistence. The low apparent rate of ongoing CTL selection in chronically infected patients, however, suggests that if CTL escape occurs during HCV infection it is probably an early event.
Former JAMA editor starts electronic journal
Authors: J. H. Tanne
Journal: BMJ (1999)

The first entirely electronic general medical journal has been launched, on the internet with Dr George Lundberg as editor in chief. Called Medscape General Medicine, it is published by Medscape, a leading internet medical site ( www.medscape.com/).

The journal is free to Medscape's subscribers, who number more than one million and who include 180000 physicians, almost 600000 healthcare professionals, and 300000 consumers.

Dr Lundberg, who was fired in …
Doctors can help "right to die" man prepare his legal case without fear of prosecution
Authors: C. Dyer
Journal: BMJ (2012)

Doctors and lawyers may investigate possible means for a man with locked-in syndrome to end his life and may prepare his case without fear of prosecution or action against them by their regulators, the High Court in London has declared.

The unprecedented declaration paves the way for a challenge to guidelines from the director of public prosecutions for England and Wales, which state that doctors and other healthcare professionals who assist a suicide are more likely to be prosecuted than relatives or friends.

The 47 year old man, named only as Martin, who had a …
Short-Term Outcomes of Acute Myocardial Infarction in Patients With Acute Kidney Injury
Authors: Caroline S. Fox, Paul Muntner, Anita Y. Chen, Karen P. Alexander, Matthew T. Roe, Stephen D. Wiviott
Journal: Circulation (2011)

Acute kidney injury (AKI) is a risk factor for long-term adverse outcomes, including acute myocardial infarction and death. However, the relationship between severity of AKI and in-hospital outcomes in the setting of acute myocardial infarction has not been well documented.The study population (n = 59,970) was drawn from the Acute Coronary Treatment and Intervention Outcomes Network (ACTION) Registry-Get With the Guidelines (GWTG), a nationwide sample of myocardial infarction patients admitted to 383 hospitals in the United States between July 2008 and September 2009. AKI was defined using absolute changes in serum creatinine (SCr; peak SCr minus admission SCr) and categorized as no AKI (SCr change, <0.3 mg/dL), mild AKI (SCr change, 0.3-<0.5 mg/dL), moderate AKI (SCr change, 0.5-<1.0 mg/dL), and severe AKI (SCr change, ≥1.0 mg/dL). Overall, 16.1% had AKI, including 6.5% with mild AKI, 5.6% with moderate AKI, and 4.0% with severe AKI. In-hospital mortality rates for those with mild, moderate, and severe AKI were 6.6%, 14.2%, and 31.8% compared with 2.1% in those without AKI. The odds ratios for in-hospital death were 2.4 (95% confidence interval, 2.0-2.7), 4.5 (95% confidence interval, 3.9-5.1), and 12.6 (95% confidence interval, 11.1-14.3) for mild, moderate, and severe AKI compared with those without AKI. Although patients with AKI were less likely to undergo early invasive care or to receive antiplatelet therapies, rates of major bleeding ranged from 8.4% (no AKI) to 32.7% (severe AKI).AKI is common and associated with mortality and bleeding, underscoring the importance of efforts to identify risk factors and to prevent AKI in acute myocardial infarction care.
Cutaneous<i>Bacillus anthracis</i>Infection
Authors: T. Casey Gallagher, Bruce E. Strober
Journal: New England Journal of Medicine (2001)

Coronary-Artery Bypass Surgery versus Stenting for Multivessel DiseaseTo the Editor: In a trial comparing coronary-artery bypass surgery with stenting for the treatment of multivessel coronary disease, Serruys et al. (April 12 issue) 1 conclude that both treatments offer protection against death, stroke, and myocardial infarction.We disagree.Whether there is "protection" can be determined only through comparison with a group of patients who are assigned to medical therapy alone.To date, no clinical trial comparing angioplasty with medical therapy for angina has demonstrated a protective effect of angioplasty in multivessel disease. 2,3Indeed, in the second Randomised Intervention Treatment of Angina (RITA-2) trial, 3 patients who underwent angioplasty had a significant 91 percent increase (a 3 percent absolute difference) in the rate of death or myocardial infarction during a median of 2.7 years of follow-up.The early randomized, controlled trials comparing coronary surgery with medical treatment also failed to show an improvement in prognosis among patients without stenosis of the left main coronary artery and with good left ventricular function. 4 Neither of these treatment options has been shown to offer protection against myocardial infarction or stroke.These results can be explained by the fact that risk of plaque rupture is determined not by the patency of the vessel but by the stability of the atheromatous plaque: most episodes of acute coronary occlusion occur in vessels with stenoses that are not flow-limiting (those resulting in a reduction of less than 70 percent in the luminal diameter). 5These two treatments are palliative, and to portray them as protective is misleading.
Language Barriers in Medicine in the United States
Authors: Steven Woloshin
Journal: JAMA (1995)

What the scalpel is to the surgeon, words are to the clinician... the conversation between doctor and patient is the heart of the practice of medicine.<sup>1</sup> The physician-patient relationship is built through communication and the effective use of language. Along with clinical reasoning, observations, and nonverbal cues, skillful use of language endows the history with its clinical power and establishes the medical interview as the clinician's most powerful tool.<sup>2-5</sup>Language is the means by which a physician accesses a patient's beliefs about health and illness,<sup>6</sup>creating an opportunity to address and reconcile different belief systems. Furthermore, it is through language that physicians and patients achieve an empathic connection that may be therapeutic in itself.<sup>7</sup> Because of language barriers, millions of US residents cannot have this connection with their physician. According to the 1990 US Census,<sup>8</sup>almost 14 million people living in the United States do
Early changes in interferon signaling define natural killer cell response and refractoriness to interferon-based therapy of hepatitis C patients
Authors: Birgit Edlich, Golo Ahlenstiel, Aintzane Zabaleta Azpiroz, Jonathan Stoltzfus, Mazen Noureddin, Elisavet Serti, Jordan J. Feld, Jake T. Liang, Yaron Rotman, Barbara Rehermann
Journal: Hepatology (2011)

Natural killer (NK) cells exhibit a polarized phenotype with increased cytotoxicity and decreased interferon gamma (IFN–γ) production in chronic hepatitis C virus (HCV) infection. Here, we asked whether this is caused by type I interferon (IFN)–induced expression and phosphorylation levels of signal transducer and activator of transcription (STAT) molecules in NK cells and whether it affects the response and refractoriness of NK cells to IFN–α–based therapy of HCV. STAT1 levels in NK cells were significantly higher in patients with chronic HCV infection than in uninfected controls. STAT1 levels and induction of phosphorylated STAT1 (pSTAT1) increased further during IFN–α–based therapy with preferential STAT1 over STAT4 phosphorylation. Induction of pSTAT1 correlated with increased NK cytotoxicity (tumor necrosis factor–apoptosis–inducing ligand [TRAIL] expression and degranulation) and decreased IFN–γ production. NK cells from patients with a greater than 2 log10 first–phase HCV RNA decline to IFN–α–based therapy (&gt;99% IFN effectiveness) displayed strong pSTAT1 induction in vivo and were refractory to further stimulation in vitro . In contrast, NK cells from patients with a less than 2 log10 first–phase HCV RNA decline exhibited lower pSTAT1 induction in vivo ( P = 0.024), but retained greater IFN–α responsiveness in vitro ( P = 0.024). NK cells of all patients became refractory to in vivo and in vitro stimulation by IFN–α during the second–phase virological response. Conclusion: These data show that IFN–α–induced modulation of STAT1/4 phosphorylation underlies the polarization of NK cells toward increased cytotoxicity and decreased IFN–γ production in HCV infection, and that NK cell responsiveness and refractoriness correlate to the antiviral effectiveness of IFN–α–based therapy. (Hepatology 2012)
Investigation and treatment of imported malaria in non-endemic countries
Authors: C. J. M. Whitty, P. L. Chiodini, D. G. Lalloo
Journal: BMJ (2013)

Every year, several thousand people with malaria arrive in non-endemic countries, and about 1600 arrive in the United Kingdom alone.][3] This rate is similar to that seen in endemic countries, but the age profile of deaths is very different.5][6] If malaria is treated early, with widely available drugs before it becomes severe, death is avoidable and a full recovery almost guaranteed.Late presentation carries a higher risk of death.The management of severe malaria is a medical emergency.This review describes how to recognise and diagnose malaria, the current treatment of uncomplicated malaria, and the management of patients with severe disease.It concentrates on adults and recent advances relevant to non-endemic high resource countries such as Europe and North America.Different challenges arise in low resource endemic settings and are not covered in this review.
Muscular Changes in Rheumatoid Arthritis
Authors: D. A. H. Yates
Journal: Annals of the Rheumatic Diseases (1963)

Atrophy and weakness of the limb muscles are extremely common in rheumatoid arthritis, the most likely causes being inhibition and disuse as a result of painful movement.However, other factors which may contribute are neurogenic atrophy as a result of a diffuse or localized neuro- pathy, direct extension of inflammatory tissue from neighbouring joints, or polymyositis arising as a manifestation of the systemic disease.Round cell nodular infiltrations of muscle have been recorded in approximately 50 per cent. of cases of rheumatoid arthritis.Although initially this appearance was claimed by Steiner, Freund, Leichtentritt, and Maun (1946) to be a specific change, this was later refuted by Sokoloff, Wilens, and Bunim (1951), who showed similar but less florid changes in 25 per cent. of non-rheumatoid subjects.Electromyographic studies in rheumatoid arth- ritis have produced conflicting reports.Thus Morrison, Short, Ludwig, and Schwab (1947) detected involuntary activity in muscles related to involved joints, but Mueller and Mead (1952) found this could invariably be stopped by careful positioning of the joints.
Does delayed gastric emptying really cause symptoms in functional dyspepsia?
Authors: M Camilleri
Journal: Gut (2006)

When the glove does fit, you should not acquit

In this month’s issue of Gut , Talley and colleagues1 report an interesting study on the opportunistic use of a database, acquired during the baseline period of four multicentre therapeutic trials, to explore the associations between gastric emptying and symptoms in functional dyspepsia (see page 933) . This was not a prospective study designed to specifically address the question posed in the title of this commentary. Before analysing the information from this study, it is opportune to review three concepts that reflect recent papers from the literature.

Firstly, combinations of symptoms are associated with abnormal gastric functions . In a scholarly review, Tack et al surmised that 40–50% of patients with dyspepsia had impaired gastric accommodation after meal ingestion, 34–66% had gastric hypersensitivity, and 23–59% had delayed gastric emptying.2 Moreover, delayed gastric emptying was associated with early satiety, nausea, vomiting and fullness; impaired gastric accommodation with early satiety and fullness, and with weight loss in two of four studies; and visceral hypersensitivity with pain, belching, and weight loss in one of four studies.2

Secondly, symptoms of dyspepsia occur in combination, and they have already been shown to be associated with delayed gastric emptying . …
President's Address: DELIVERED AT THE OPENING OF THE SEVENTEENTH INTERNATIONAL MEDICAL CONGRESS
Authors: T. Barlow
Journal: BMJ (1913)

GENTLEMEN,-A wlhole generation has passed away since tlho International Medical Congress last met in London.What a nmagnificent galaxy of talent in medicine, suirgery, and pathology was gathered round the Prince of AVales, wlho was our Royal Patron at that time !It is fitting that we should follow the admonition of Ecclesiastics -and praise famous men and the fathers that begat us.Our President, Sir James Paget, was a great clinical pathologist.His mind was stored witlh all that was then knoVDn of tlhe morbid anatomy of surgical disease and injury, and of tlle fainily re- lationships of the different diatheses.He was a splendid teacher and possessed a lticid eloquence and a nioral fervour not excelled bv any of hiis contemporaries.Jenner and GuLll, Wilks and (Gairdner were our great teaclhers of clinical medicine.Each of them based his knowledge on the sure foundation of the 1iost-mortemn room and the hospital wards.We shall not see their like again, for their careers began before the days of specialization, and they were amongst the last of the great general
Tiotropium or salmeterol as add-on therapy to inhaled corticosteroids for patients with moderate symptomatic asthma: two replicate, double-blind, placebo-controlled, parallel-group, active-comparator, randomised trials
Authors: Huib A M Kerstjens, Thomas B Casale, Eugene R Bleecker, Eli O Meltzer, Emilio Pizzichini, Olaf Schmidt, Michael Engel, Loek Bour, Cynthia B Verkleij, Petra Moroni-Zentgraf, Eric D Bateman
Journal: The Lancet Respiratory Medicine (2015)
Hamish Meldrum elected BMA chairman
Authors: Zosia Kmietowicz
Journal: BMJ (2007)

Dr Hamish Meldrum, a GP from East Yorkshire, has been elected chairman of the BMA council.

Dr Meldrum, who has been chairman of the BMA's general practitioners' committee since 2004, was elected in a three way contest at a meeting of the BMA Council on Thursday (28 June), following the …
Acetaminophen Increases Blood Pressure in Patients With Coronary Artery Disease
Authors: Isabella Sudano, Andreas J. Flammer, Daniel Périat, Frank Enseleit, Matthias Hermann, Mathias Wolfrum, Astrid Hirt, Priska Kaiser, David Hurlimann, Michel Neidhart, Steffen Gay, Johannes Holzmeister, Juerg Nussberger, Pavani Mocharla, Ulf Landmesser, Sarah R. Haile, Roberto Corti, Paul M. Vanhoutte, Thomas F. Lüscher, Georg Noll, Frank Ruschitzka
Journal: Circulation (2010)

Background— Because traditional nonsteroidal antiinflammatory drugs are associated with increased risk for acute cardiovascular events, current guidelines recommend acetaminophen as the first-line analgesic of choice on the assumption of its greater cardiovascular safety. Data from randomized clinical trials prospectively addressing cardiovascular safety of acetaminophen, however, are still lacking, particularly in patients at increased cardiovascular risk. Hence, the aim of this study was to evaluate the safety of acetaminophen in patients with coronary artery disease. Methods and Results— The 33 patients with coronary artery disease included in this randomized, double-blind, placebo-controlled, crossover study received acetaminophen (1 g TID) on top of standard cardiovascular therapy for 2 weeks. Ambulatory blood pressure, heart rate, endothelium-dependent and -independent vasodilatation, platelet function, endothelial progenitor cells, markers of the renin-angiotensin system, inflammation, and oxidative stress were determined at baseline and after each treatment period. Treatment with acetaminophen resulted in a significant increase in mean systolic (from 122.4±11.9 to 125.3±12.0 mm Hg P =0.02 versus placebo) and diastolic (from 73.2±6.9 to 75.4±7.9 mm Hg P =0.02 versus placebo) ambulatory blood pressures. On the other hand, heart rate, endothelial function, early endothelial progenitor cells, and platelet function did not change. Conclusions— This study demonstrates for the first time that acetaminophen induces a significant increase in ambulatory blood pressure in patients with coronary artery disease. Thus, the use of acetaminophen should be evaluated as rigorously as traditional nonsteroidal antiinflammatory drugs and cyclooxygenase-2 inhibitors, particularly in patients at increased cardiovascular risk. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00534651.
About the role and underlying mechanisms of cofactors in anaphylaxis
Authors: F. Wölbing, J. Fischer, M. Köberle, S. Kaesler, T. Biedermann
Journal: Allergy (2013)

Abstract Anaphylaxis is the systemic and most severe presentation of type I allergy. A number of conditions were identified that modulate the onset of anaphylaxis such as co‐ or augmentation factors, which significantly lower the allergen dose necessary for triggering anaphylaxis. Next to physical exercise or alcohol consumption, co‐administration of nonsteroidal anti‐inflammatory drugs ( NSAID ) or concomitant infectious diseases are well‐documented cofactors of anaphylaxis. Registries for anaphylaxis document a role for cofactors in about 30% of anaphylactic reactions. Some disease entities such as ‘wheat‐dependent exercise‐induced anaphylaxis’ ( WDEIA ) are explicitly characterized by elicitation of anaphylaxis only in the presence of at least one such cofactor. Using WDEIA as a model disease, studies demonstrated that exercise increases skin prick test reactivity to and bioavailability of the allergen. Additional data indicate that alcohol consumption and NSAID administration display similar effects. Modulation of the cellular activation threshold is another mechanism underlying cofactor‐induced anaphylaxis, most likely also functional when infectious diseases orchestrate elicitation of anaphylaxis. Cofactors are increasingly accepted to play a fundamental role in eliciting anaphylaxis. Consequently, to improve patient management modalities, a better understanding of the underlying mechanisms is warranted. This review aims to update clinicians and clinical scientists on recent developments.
Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia
Authors: Eliano Pio Navarese, Michalina Kołodziejczak, Volker Schulze, Paul A. Gurbel, Udaya Tantry, Yingfeng Lin, Maximilian Brockmeyer, David E. Kandzari, Julia M. Kubica, Ralph B. D'Agostino, Jacek Kubica, Massimo Volpe, Stefan Agewall, Dean J. Kereiakes, Malte Kelm
Journal: Annals of Internal Medicine (2015)

Guidelines recommend statins as first-line therapy for dyslipidemia. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new lipid-lowering approach.To assess the efficacy and safety of PCSK9 antibodies in adults with hypercholesterolemia.MEDLINE, PubMed Central, and Google Scholar; conference proceedings; and the ClinicalTrials.gov registry through 4 April 2015.Phase 2 or 3 randomized, controlled trials (RCTs) comparing treatment using PCSK9 antibodies with no anti-PCSK9 therapy in adults with hypercholesterolemia.Two investigators independently extracted data on study characteristics and lipid and clinical outcomes, and rated risk of bias of trials. Prespecified primary end points were all-cause and cardiovascular mortality.Twenty-four RCTs comprising 10 159 patients were included. Compared with no antibody, treatment with PCSK9 antibodies led to marked reductions in low-density lipoprotein cholesterol levels (mean difference, -47.49% [95% CI, -69.64% to -25.35%]; P < 0.001] and other atherogenic lipid fractions, and it reduced all-cause mortality (odds ratio [OR], 0.45 [CI, 0.23 to 0.86]; P = 0.015; heterogeneity P = 0.63; I2 = 0%) and cardiovascular mortality (OR, 0.50 [CI, 0.23 to 1.10]; P = 0.084; heterogeneity P = 0.78; I2 = 0%). The rate of myocardial infarction was significantly reduced with use of PCSK9 antibodies (OR, 0.49 [CI, 0.26 to 0.93]; P = 0.030; heterogeneity P = 0.45; I2 = 0%), and increases in the serum creatine kinase level were reduced (OR, 0.72 [CI, 0.54 to 0.96]; P = 0.026; heterogeneity P = 0.65; I2 = 0%). Serious adverse events did not increase with administration of PCSK9 antibodies.Results were derived from study-level data rather than patient-level data, and clinical outcome data are rare.PCSK9 antibodies seem to be safe and effective for adults with dyslipidemia.CRC 1116 Masterswitches in Myocardial Ischemia, German Research Council DFG.
Ambient Air Pollution and Low Birth Weight in Connecticut and Massachusetts
Authors: Michelle L. Bell, Keita Ebisu, Kathleen Belanger
Journal: Environmental Health Perspectives (2007)

Several studies have examined whether air pollution affects birth weight; however results vary and many studies were focused on Southern California or were conducted outside of the United States.We investigated maternal exposure to particulate matter with aerodynamic diameter < 10, < 2.5 microm (PM(10), PM(2.5)), sulfur dioxide, nitrogen dioxide, and carbon monoxide and birth weight for 358,504 births in Massachusetts and Connecticut from 1999 to 2002.Analysis included logistic models for low birth weight (< 2,500 g) and linear models with birth weight as a continuous variable. Exposure was assigned as the average county-level concentration over gestation and each trimester based on mother's residence. We adjusted for gestational length, prenatal care, type of delivery, child's sex, birth order, weather, year, and mother's race, education, marital status, age, and tobacco use.An interquartile increase in gestational exposure to NO(2), CO, PM(10), and PM(2.5) lowered birth weight by 8.9 g [95% confidence interval (CI), 7.0-10.8], 16.2 g (95% CI, 12.6-19.7), 8.2 g (95% CI, 5.3-11.1), and 14.7 g (95% CI, 12.3-17.1), respectively. Lower birth weight was associated with exposure in the third trimester for PM(10), the first and third trimesters for CO, the first trimester for NO(2) and SO(2), and the second and third trimesters for PM(2.5). Effect estimates for PM(2.5) were higher for infants of black mothers than those of white mothers.Results indicate that exposure to air pollution, even at low levels, may increase risk of low birth weight, particularly for some segments of the population.