tbuckley/cabot-search huggingface dataset:
Detection of Atrial Fibrillation and Flutter by a Dual-Chamber Implantable Cardioverter-Defibrillator
Authors: Charles D. Swerdlow, Wolfgang Schšls, Barbara Dijkman, Werner Jung, Nirav V. Sheth, Walter H. Olson, Bruce D. Gunderson, for the Worldwide Jewel AF Investigators
Journal: Circulation (2000)

To distinguish prolonged episodes of atrial fibrillation (AF) that require cardioversion from self-terminating episodes that do not, an atrial implantable cardioverter-defibrillator (ICD) must be able to detect AF continuously for extended periods. The ICD should discriminate between atrial tachycardia/flutter (AT), which may be terminated by antitachycardia pacing, and AF, which requires cardioversion.We studied 80 patients with AT/AF and ventricular arrhythmias who were treated with a new atrial/dual-chamber ICD. During a follow-up period lasting 6+/-2 months, we validated spontaneous, device-defined AT/AF episodes by stored electrograms in all patients. In 58 patients, we performed 80 Holter recordings with telemetered atrial electrograms, both to validate the continuous detection of AT/AF and to determine the sensitivity of the detection of AT/AF. Detection was appropriate in 98% of 132 AF episodes and 88% of 190 AT episodes (98% of 128 AT episodes with an atrial cycle length <300 ms). Intermittent sensing of far-field R waves during sinus tachycardia caused 27 inappropriate AT/AF detections; these detections lasted 2.6+/-2.0 minutes. AT/AF was detected continuously in 27 of 28 patients who had spontaneous episodes of AT/AF (96%). The device memory recorded 90 appropriate AT/AF episodes lasting >1 hour, for a total of 2697 hours of continuous detection of AT/AF. During Holter monitoring, the sensitivity of the detection of AT/AF (116 hours) was 100%; the specificity of the detection of non-AT/AF rhythms (1290 hours) was 99.99%. Of 166 appropriate episodes detected as AT, 45% were terminated by antitachycardia pacing.A new ICD detects AT/AF accurately and continuously. Therapy may be programmed for long-duration AT/AF, with a low risk of underdetection. Discrimination of AT from AF permits successful pacing therapy for a significant fraction of AT.
Tuberculosis Transmission in the 1990s
Authors: Margaret A. Hamburg, Thomas R. Frieden
Journal: New England Journal of Medicine (1994)

Two studies reported in this issue of the Journal1,2 use new techniques of molecular epidemiology to extend our understanding of the transmission and control of an ancient disease -- tuberculosis. The conventional wisdom has been that 90 percent of active cases arose from foci of infection first acquired years or decades ago. In the United States alone, the pool of persons with latent tuberculous infection is estimated at 10 to 15 million3. But where do today's active cases come from? The reports in this issue suggest that at least in San Francisco and New York City, a third . . .
OBSTRUCTION AND CONSEQUENT DETENTION THE CAUSE OF APPENDICITISAS PROVED BY CASES AND BY EXPERIMENTAL APPENDICITIS IN DOGS.
Authors: C. VAN ZWALENBURG
Journal: JAMA (1904)

We frequently find an obstructed and overdistended appendix, and the earlier in the attack the appendix is seen the more frequently is this condition observed. It is constantly mentioned by writers, and is by several connected with the production of gangrene, notably by Hartley,<sup>1</sup>Ochsner<sup>2</sup>and Hemmeter.<sup>3</sup>Robert Abbe<sup>4</sup>has made mention of this condition in connection with his study of stricture and recurring appendicitis. Dieulafoy<sup>5</sup>has said much about his theory of a closed sack and its effect in increasing the virulence of bacteria. I fail to find, however, any reference to the resulting hydraulic pressure on the blood vessels of the mucosa and submucosa and the consequent blood stasis in the inner layers of the entire wall of the distended sack. This is to me the important missing link between constriction and infection, and the point toward which this paper is principally directed. The appendix has a firm
Topical chemoprophylaxis with silver sulphadiazine and silver nitrate chlorhexidine creams: emergence of sulphonamide-resistant Gram-negative bacilli.
Authors: E J Lowbury, J R Babb, K Bridges, D M Jackson
Journal: BMJ (1976)

Controlled trials of 0.5% silver nitrate compresses (SN), 1% silver sulphadiazine cream (SSD), and a cream containing 0.5% silver nitrate and 0.2% chlorhexidine digluconate (SNC) showed that all were comparably effective in protecting burns from infection. SN compresses were much less active against miscellaneous Gram-negative bacilli than the other preparations, and the mean morning and evening temperatures and respiration rates in the patients treated with SN compresses were higher then those of patients treated with SSD. Pseudomonas aeruginosa and Proteus spp, though rare in all groups, were less often found in the patients treated with SN compresses. Sulphonamide-resistant Gram-negative bacilli became predominant during the trial of SSD cream on extensive burns and the prophylactic effectiveness of that preparation was thus reduced in the later stages of the trial.
Reduced Expression of Anti-Viral Molecules by Blood Mononuclear Cells is Associated With Asthma, but not with Atopy per se.
Authors: J.W. Upham, S.T. Yerkovich, A. Poh, P.D. Sly, P.G. Holt, M. Roponen
Journal: Journal of Allergy and Clinical Immunology (2009)
BLOOD VESSELS IN FAT TISSUE. RELATION TO PROBLEMS OF GAS EXCHANGE
Authors: Isidore Gersh, Mary A. Still
Journal: The Journal of Experimental Medicine (1945)

1. The ratio of the surface of the capillary bed to the volume of tissue supplied by the vessels (S/V ratio) for both open and closed capillaries in fat-rich tissue of the rat is 51.9, in fat-poor tissue of the same sort 222.2. About one-half of the capillaries in fat-rich tissue, to one-fourth in fat-poor tissue, are open during ordinary activity. The total capillary bed of fat-rich tissue is one-third as great as in muscle; the total capillary bed of fat-poor tissue has about the same density as that of the most poorly supplied muscle. This establishes the fact quantitatively that the capillary bed of fat is relatively inadequate, compared to other tissues, for transferring inert gases from fat tissue at a sufficiently rapid rate to prevent the occurrence of extravascular bubbles following rapid decompression from high pressure atmospheres. It also explains the greater distention of the blood vessels in fat tissue, due to gas, than in any other tissue following decompression. The observations have a bearing also on the estimation of the permeability of the blood-fat barrier to inert gases. 2. The volume of protoplasm of fat cells may be very small; a method is presented for estimating it quantitatively. Since it alone is important in metabolism, recalculation of the basic data on a basis of the ratio of surface area of capillaries to volume of protoplasm of fat cell in fat tissue yields a more useful figure. For fat-rich fat tissue S/V (protoplasm) = 2159.0 (for total capillary surface) or 977.6 (for open capillary surface). This means that for purpose of metabolism, the capillary bed is far richer than that of muscle.
Smoking, Coronary Artery Occlusion, and Nonfatal Myocardial Infarction
Authors: Arthur J. Hartz
Journal: JAMA (1981)

The association of smoking with a history of myocardial infarction (MI) was studied in 3,997 men who had coronary arteriography. The patients were subdivided into groups based on coronary occlusion (minimal, moderate, or severe) and plasma cholesterol level (low, moderate, or high). For men older than 50 years, smoking was significantly associated with MI in each occlusion group. For men younger than 50 years, the association was significant for men with moderate or severe occlusion. In the presence of higher cholesterol levels there was a stronger association of smoking with MI, but a weaker association of smoking with coronary occlusion. These results suggest that the association of smoking with MI does not depend primarily on the atherogenic effect of smoking. The association seems to be enhanced by high levels of coronary occlusion and cholesterol. (<i>JAMA</i>1981;246:851-853)
Why Physicians Order Tests
Authors: Deborah Grady
Journal: JAMA Internal Medicine (2013)

Claims Act permits medical malpractice lawsuits against federally employed physicians, the substantial majority of claims are resolved through administrative processes.Only 3 judgments against the US government were recorded for tort claims in 2010. 6We did not detect a significant reduction in inappropriate testing in the VA environment, which suggests a lesser role of defensive medicine and self-referral in the inappropriate use of MPI.A recent survey of cardiologists did not find any association between ownership of diagnostic equipment (MPI, catheterization laboratory, computed tomography scanner, or echocardiography laboratory) and concordance with appropriateness categories. 7 The magnitude and pattern of inappropriate testing in our investigation are similar to those in prior reports. 3Hendel et al 8 observed similar common inappropriate MPI indications, as well as significant associations between asymptomatic patients and inappropriate testing (OR, 22.5 [95% CI,) and lower likelihood of inappropriate testing in patients with diabetes mellitus (OR, 0.4 [95% CI, 0.4-0.5]).Reasons for the observed patterns of ordering MPI are unclear.Conceivably, commonalities in medical training, independent of postgraduate practice environment, could contribute to an exaggerated perception of benefit of MPI in asymptomatic patients and those at low risk of coronary heart disease.This exaggerated perception of the benefit would also seem to hold true for preoperative risk assessment, with the majority of preoperative MPI in our study having been inappropriately ordered.
Abstract 431: Nuclear WRAP53 is associated with positive response to radiotherapyand improved overall survival in head and neck squamous cell carcinoma.
Authors: Karin B. Roberg, Stina Garvin, Katharina Tiefenböck, Lovisa Farnebo, Marianne Farnebo
Journal: Cancer Research (2013)

Abstract Purpose: Today there are no reliable predictive markers for radiotherapy response in head and neck squamous cell carcinoma (HNSCC), leading to both under-and over-treatment of patients, personal suffering and negative socio-economic effects. There is therefore a great need to develop new markers to provide patients with these tumors individualized and more effective treatment. WRAP53 is a natural antisense transcript to p53 that regulates levels of endogenous p53 mRNA and the induction of p53 in response to DNA damage. In addition, WRAP53 protein has been shown to be an essential component of nuclear organelles called Cajal bodies and involved in a variety of vital cellular functions such as splicing and telomerase activity. The aim of this study was to investigate WRAP53 as a potential predictive marker of radiotherapy response in head and neck squamous cell carcinoma (HNSCC) patients. Materials and methods: Investigations were performed on tumor biopisies from patients classified as responders or non-responders to radiotherapy. Protein expression was examined using immunohistochemistry. After downregulation of WRAP53 by siRNA, assessment of intrinsic radiosensitivity was performed on two HNSCC cell lines. Results: Nuclear WRAP53 expression was significantly associated with better response to radiotherapy (binary regression analysis, p = 0.029) and patients with nuclear WRAP53 had a significantly better survival (p = 0.014). Downregulation of WRAP53 with siRNA in vitro increased resistance to radiation (p &amp;lt; 0.001). Conclusions: Our study suggests that the nuclear location of WRAP53 is of importance in mediating tumor response to radiotherapy. Further studies are needed to investigate nuclear WRAP53 as a potential predictive marker of radiotherapy response in HNSCC. Citation Format: Karin B. Roberg, Stina Garvin, Katharina Tiefenböck, Lovisa Farnebo, Marianne Farnebo. Nuclear WRAP53 is associated with positive response to radiotherapyand improved overall survival in head and neck squamous cell carcinoma. [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 431. doi:10.1158/1538-7445.AM2013-431
Rheumatoid factor amplifies the macrophage secretion of TNF induced by ACPA-citrullinated fibrinogen immune complexes
Authors: L Laurent, C Clavel, J-L Pasquali, G Serre, M Sebbag
Journal: Annals of the Rheumatic Diseases (2010)

Based on their tight specifi city for the disease, their association to its most severe forms and their production in the infl amed synovial tissue where citrullinated fi brin, their main antigenic target, is also abundant, the autoantibodies to citrullinated proteins (ACPA) probably play a central role in the pathophysiology of rheumatoid arthritis (RA).To substantiate this hypothesis the authors developed an original and totally human in vitro model in which monocyte-derived macrophages from healthy donors are stimulated with ACPA-containing immune complexes (ACPA-IC) generated by capturing ACPA on immobilised citrullinated fi brinogen.Using this model, the authors confi rmed the proinfl ammatory potential of ACPA-IC, as their interaction with macrophages induced TNFα secretion.As IgM rheumatoid factor (RF) is an autoantibody directed to the Fc fragment of IgG, as it is also on August 18,
Angiopoietin-2 promotes inflammatory activation of human macrophages and is essential for murine experimental arthritis
Authors: Sarah Krausz, Samuel Garcia, Carmen A Ambarus, Daphne de Launay, Martyn Foster, Brian Naiman, William Iverson, Jane R Connor, Matthew A Sleeman, Anthony J Coyle, Jorg Hamann, Dominique Baeten, Paul P Tak, Kris A Reedquist
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Angiopoietin (Ang)-1 and Ang-2, and their shared receptor Tie2, are expressed in rheumatoid arthritis (RA) synovial tissue, but the cellular targets of Ang signalling and the relative contributions of Ang-1 and Ang-2 to arthritis are poorly understood. <h3>Objectives</h3> To determine the cellular targets of Ang signalling in RA synovial tissue, and the effects of Ang-2 neutralisation in murine collagen-induced arthritis (CIA). <h3>Methods</h3> RA and psoriatic arthritis (PsA) synovial biopsies were examined for expression of Tie2 and activated phospho (p)-Tie2 by quantitative immunohistochemistry and immunofluorescent double staining. Human monocyte and macrophage Tie2 expression was determined by flow cytometry and quantitative PCR. Regulation of macrophage intracellular signalling pathways and gene expression were examined by immunoblotting and ELISA. CIA was assessed in mice treated with saline, control antibody, prednisolone or neutralising anti-Ang-2 antibody. <h3>Results</h3> Expression of synovial Tie2 and p-Tie2 was similar in RA and PsA. Tie2 activation in RA patient synovial tissue was predominantly localised in synovial macrophages and was expressed by human macrophage. Ang-1 and Ang-2 stimulated activation of multiple intracellular signalling pathways, and cooperated with tumour necrosis factor to induce macrophage interleukin 6 and macrophage inflammatory protein 1α production. Ang-2 selectively suppressed macrophage thrombospondin-2 production. Ang-2 neutralisation significantly decreased disease severity, synovial inflammation, neo-vascularisation and joint destruction in established CIA. <h3>Conclusions</h3> The authors identify synovial macrophages as primary targets of Ang signalling in RA, and demonstrate that Ang-2 promotes the pro-inflammatory activation of human macrophages. Ang-2 makes requisite contributions to pathology in CIA, indicating that targeting Ang-2 may be of therapeutic benefit in the treatment of RA.
Value of prescribing heroin is uncertain
Authors: S. Mayor
Journal: BMJ (2003)

More research should be carried out into the effectiveness of prescribing heroin for addicts before the treatment is expanded in Britain, recommended a review published last week.

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Heroin addicts in Massachusetts

Credit: AP PHOTO/ANDREW SULLIVAN

The review found that the evidence base for prescribing heroin was relatively weak, with only a few studies evaluating its effectiveness.

One of the review's authors, Nicky Metrebian, …

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The discovery and development of analgesics: new mechanisms, new modalities
Authors: Gillian Burgess, Dic Williams
Journal: Journal of Clinical Investigation (2010)

Despite intensive research into pain mechanisms and significant investment in research and development, the majority of analgesics available to prescribers and patients are based on mechanistic classes of compounds that have been known for many years. With considerable ingenuity and innovation, researchers continue to make the best of the mechanistic approaches available, with novel formulations, routes of administration, and combination products. Here we review some of the mechanisms and modalities of analgesics that have recently entered into clinical development, which, coupled with advances in the understanding of the pathophysiology of chronic pain, will hopefully bring the promise of new therapeutics that have the potential to provide improved pain relief for those many patients whose needs remain poorly met.
Acquired deficiencies of protein S. Protein S activity during oral anticoagulation, in liver disease, and in disseminated intravascular coagulation.
Authors: A D'Angelo, S Vigano-D'Angelo, C T Esmon, P C Comp
Journal: Journal of Clinical Investigation (1988)

Protein S is a vitamin K-dependent plasma protein which serves as the cofactor for activated protein C. Protein S circulates in both an active, free form and in an inactive complex with C4b-binding protein. To elucidate the role of protein S in disease states and during oral anticoagulation, we developed a functional assay for protein S that permits evaluation of the distribution of protein S between free and bound forms and permits determination of the specific activity of the free protein S. In liver disease, free protein S antigen is moderately reduced and the free protein S has significantly reduced specific activity. In disseminated intravascular coagulation, reduced protein S activity occurs due to a redistribution of protein S to the inactive bound form. During warfarin anticoagulation, reduction of free protein S antigen and the appearance of forms with abnormal electrophoretic mobility significantly decrease protein S activity. After the initiation of warfarin, the apparent half-life of protein S is 42.5 h. In patients with thromboembolic disease, transient protein S deficiency occurs due to redistribution to the complexed form. Caution should be exercised in diagnosing protein S deficiency in such patients by use of functional assays.
Age-dependent cardiomyopathy and heart failure phenotype in mice overexpressing β2-adrenergic receptors in the heart
Authors: X Du
Journal: Cardiovascular Research (2000)

Objective: To explore long-term cardiac phenotype in transgenic (TG) mice with 300-fold overexpression of β2-adrenergic receptors (AR). Methods: Echocardiography was performed serially on a cohort of wild-type and TG mice (n = 26 each) between 4 and 15 months of age. Survival was monitored and autopsy and histological examinations were performed. Results: Heart rate was higher in TG than in wild-type mice throughout the study period. The left ventricular dimensions and fractional shortening were similar between TG and wild-type groups during 4–6 months. Starting at 9 months, however, TG mice showed progressive reduction in fractional shortening and systolic wall thickening, and increase in left ventricular dimensions and left ventricular mass, indicating onset of heart failure, left ventricular hypertrophy and remodeling. Abnormal waveforms in the electrocardigram and episodes of ventricular ectopic beats were also observed in TG mice. Death of TG mice started at 8.5 months, and the cumulative mortality was 81% by 15 months (P<0.0001 vs. 4% in wild-type mice). The majority of deaths were due to severe heart failure, indicated by cardiac dilatation, lung congestion, pleural effusion and atrial thrombus. Left ventricular sections showed widespread interstitial fibrosis, loss of myocytes and myocyte hypertrophy in TG mice. Conclusions: A high level of β2AR overexpression results in cardiomyopathy and heart failure. The onset was slower and the expression levels of receptors required are much higher than previously described for the β1AR overexpression.
Benign Subcutaneous Emphysema of the Upper Extremity
Authors: James S Winshall, Barbara N Weissman
Journal: New England Journal of Medicine (2005)

A 59-year-old woman fell from a horse and injured her left elbow. Four days later she sought evaluation for persistent swelling of her arm. On examination, the patient had a small, clean wound over the olecranon; there were no signs of infection. Diffuse crepitus of the arm, extending to the left chest wall, was noted. An oblique radiograph of the elbow (Panel A) and a posteroanterior radiograph of the chest (Panel B) demonstrated circumferential subcutaneous emphysema (arrows) of the upper extremity extending from the wrist to the left hemithorax. No rib fracture or pneumothorax was seen. The absence of air . . .
Serum lipid elevation during isotretinoin therapy for acne in the West of Scotland
Authors: B.R. WALKER, RONA M. MacKIE
Journal: British Journal of Dermatology (1990)

We have studied 116 patients in the West of Scotland receiving isotretinoin for acne vulgaris at a dose of 1 mg/kg per day. No clinical evidence of adverse effects resulting from lipid elevations were seen in the short term. Cholesterol levels rose during the first 6 weeks of therapy, and thereafter stabilized, but triglyceride levels rose after 6 weeks therapy and continued to rise while therapy continued. Pretreatment levels of neither lipid was predictive of the level of elevation observed while on therapy. No other predictors of lipid elevation such as age or sex were identified in this study, which is the largest reported of patients receiving the standard recommended dose of isotretinoin.
Complete Interruption of the Aortic Arch
Authors: WILLIAM C. ROBERTS, ANDREW G. MORROW, EUGENE BRAUNWALD
Journal: Circulation (1962)

The clinical, hemodynamic, angiographic, and pathologic findings in three patients with complete interruption of the aortic arch are presented. In addition, data derived from published reports of 52 previous patients are summarized. This malformation is never an isolated one, since a patent ductus arteriosus is always present and a ventricular septal defect is almost invariably found as well. The diagnosis of absence of the aortic arch is difficult, since differential cyanosis is uncommon, relative systolic hypertension of the arms is rare, and the heart murmur, when present, is of a nonspecific nature. At catheterization the pressure in the pulmonary artery, patent ductus arteriosus, and descending aorta is usually similar to that in the ascending aorta and in its branches. Selective angiocardiography has been shown to be the only means of establishing the presence of the malformation prior to operation or autopsy. Since the majority of patients with absence of the aortic arch die within the month following birth, early recognition of the lesion is imperative if surgical correction is to be of benefit.