tbuckley/cabot-search huggingface dataset:
Transseptal pressure gradient and diastolic ventricular septal motion in patients with mitral stenosis.
Authors: C R Thompson, I Kingma, R P MacDonald, I Belenkie, J V Tyberg, E R Smith
Journal: Circulation (1987)

Previous studies from our laboratory have shown that the position of the ventricular septum relative to the two ventricles at end-diastole is determined by the instantaneous transseptal pressure gradient (TSG) defined as left ventricular minus simultaneous right ventricular pressure. Since patients with mitral stenosis often have exaggerated leftward (paradoxic) motion of the ventricular septum during early diastole, we studied seven patients with mitral stenosis undergoing cardiac catheterization to determine if position (and therefore motion) of the ventricular septum was determined by TSG throughout diastole. M Mode echocardiograms derived from a two-dimensional parasternal short-axis view were recorded with simultaneous micromanometer measurements of left ventricular and right ventricular pressures. Six of seven patients demonstrated abnormal early diastolic leftward motion of the ventricular septum in at least one cardiac cycle. TSG measured at intervals throughout diastole ranged from -2.5 to +20 mm Hg, with abnormal TSG observed in most of the 40 cardiac cycles selected for analysis. The intracardiac position of the ventricular septum, defined as the distance from the right ventricular epicardium (RVEpi) to the left surface of the ventricular septum normalized for total cardiac dimension (RVEpi-VS), was plotted against left ventricular pressure, right ventricular pressure, and TSG. Linear regression of pooled data from all patients (164 observations) demonstrated a highly significant correlation between the instantaneous TSG and the relative intracardiac position of the ventricular septum (RVEpi-VS = 1.52 TSG + 42.7; r = .79, p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Pathology and Probabilities
Authors: William B. Schwartz, Hubert J. Wolfe, Stephen G. Pauker
Journal: New England Journal of Medicine (1981)

Abstract Pathologists typically analyze biopsy specimens and report their opinions in a qualitative fashion. Clinical information, often fragmentary in character, is implicitly linked with the histologic findings, and interpretations are couched in ambiguous language: "consistent with," "highly suggestive of," "may represent," or "cannot exclude." Only pathognomonic or normal findings are reported in an unequivocal fashion. In this paper we compare the analysis of biopsy material by a conventional method and by a numerical, probabilistic technique. We suggest that applying a probabilistic technique can considerably improve the precision of tissue diagnosis and can greatly facilitate the communication of pathologists with clinicians and with each other. Probabilistic analysis is also likely to be of substantial value in improving the interpretation and reporting of x-ray and nuclear-medicine studies. (N Engl J Med. 1981; 305:917–23.)
Abnormal sarcoplasmic reticulum Ca2+activity and uptake in human heart failure
Authors: Ulrich Schmidt, Maria Carles, Roger J. Hajjar, Thomas G. DiSalvo, Marc J. Semigran, G.William Dec, Jagat Narula, Ban-An Khaw, Judith K. Gwathmey
Journal: Journal of the American College of Cardiology (1996)
Topical application of acidified nitrite to the nail renders it antifungal and causes nitrosation of cysteine groups in the nail plate
Authors: M.J. Finnen, A. Hennessy, S. McLean, Y. Bisset, R. Mitchell, I.L. Megson, R. Weller
Journal: British Journal of Dermatology (2007)

Background Topical treatment of nail diseases is hampered by the nail plate barrier, consisting of dense cross-linked keratin fibres held together by cysteine-rich proteins and disulphide bonds, which prevents penetration of antifungal agents to the focus of fungal infection. Acidified nitrite is an effective treatment for tinea pedis. It releases nitric oxide (NO) and other NO-related species. NO can react with thiol (-SH) groups to form nitrosothiols (-SNO). Objectives To determine whether acidified nitrite can penetrate the nail barrier and cure onychomycosis, and to determine whether nitrosospecies can bind to the nail plate. Methods Nails were treated with a mixture of citric acid and sodium nitrite in a molar ratio of 0·54 at either low dose (0·75%/0·5%) or high dose (13·5%/9%). Immunohistochemistry, ultraviolet-visible absorbance spectroscopy and serial chemical reduction of nitrosospecies followed by chemiluminescent detection of NO were used to measure nitrosospecies. Acidified nitrite-treated nails and the nitrosothiols S-nitrosopenicillamine (SNAP) and S-nitrosoglutathione (GSNO) were added to Trichophyton rubrum and T. mentagrophytes cultures in liquid Sabouraud medium and growth measured 3 days later. Thirteen patients with positive mycological cultures for Trichophyton or Fusarium species were treated with topical acidified nitrite for 16 weeks. Repeat mycological examination was performed during this treatment time. Results S-nitrothiols were formed in the nail following a single treatment of low- or high-dose sodium nitrite and citric acid. Repeated exposure to high-dose acidified nitrite led to additional formation of N-nitrosated species. S-nitrosothiol formation caused the nail to become antifungal to T. rubrum and T. mentagrophytes. Antifungal activity was Cu2+ sensitive. The nitrosothiols SNAP and GSNO were also found to be antifungal. Topical acidified nitrite treatment of patients with onychomycosis resulted in > 90% becoming culture negative for T. rubrum. Conclusions Acidified nitrite cream results in the formation of S-nitrosocysteine throughout the treated nail. Acidified nitrite treatment makes a nail antifungal. S-nitrosothiols, formed by nitrosation of nail sulphur residues, are the active component. Acidified nitrite exploits the nature of the nail barrier and utilizes it as a means of delivery of NO/nitrosothiol-mediated antifungal activity. Thus the principal obstacle to therapy in the nail becomes an effective delivery mechanism.
Caspase-mediated Cleavage of Focal Adhesion Kinase pp125FAK and Disassembly of Focal Adhesions in Human Endothelial Cell Apoptosis
Authors: Bodo Levkau, Barbara Herren, Hidenori Koyama, Russell Ross, Elaine W. Raines
Journal: The Journal of Experimental Medicine (1998)

Normal endothelial and epithelial cells undergo apoptosis when cell adhesion and spreading are prevented, implying a requirement for antiapoptotic signals from the extracellular matrix for cell survival. We investigated some of the molecular changes occurring in focal adhesions during growth factor deprivation–induced apoptosis in confluent monolayers of human umbilical vein endothelial cells. Among the first morphologic changes after initiation of the apoptotic process are membrane blebbing, loss of focal adhesion sites, and retraction from the matrix followed by detachment. We observe a specific proteolytic cleavage of focal adhesion kinase (pp125FAK), an important component of the focal adhesion complex, and identify pp125FAK as a novel substrate for caspase-3 and caspase-3–like apoptotic caspases. The initial cleavage precedes detachment, and coincides with loss of pp125FAK and paxillin from focal adhesion sites and their redistribution into the characteristic membrane blebs of apoptotically dying cells. Cleavage of pp125FAK differentially affects its association with signaling and cytoskeletal components of the focal adhesion complex; binding of paxillin, but not pp130Cas (Cas, Crk-associated substrate) and vinculin, to the COOH terminally truncated pp125FAK is abolished. Therefore, caspase-mediated cleavage of pp125FAK may be participating in the disassembly of the focal adhesion complex and actively interrupting survival signals from the extracellular matrix, thus propagating the cell death program.
Reviews and Notes: Ethics: Standard of Care: The Law of American Bioethics
Authors: Edmund L. Erde
Journal: Annals of Internal Medicine (1994)

Literature of Medicine1 March 1994Reviews and Notes: Ethics: Standard of Care: The Law of American BioethicsEdmund L. ErdeEdmund L. ErdeUniversity of Medicine and Dentistry of New Jersey, Stratford, NJ 08084Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-5-199403010-00047 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Standard of Care: The Law of American BioethicsGeorge J. Annas. 291 pages. New York: Oxford University Press; 1993. $29.95.Bioethics is structured through many sources. George J. Annas contends that none is as influential as law, specifically constitutional, commercial, and public policy law. Under constitutional rights, Annas discusses abortion, surrogate motherhood, and refusing life-saving or psychiatric treatment. A topic under commercial law is whether drug companies should be free to sell untested medications (for example, to desperate persons infected with the human immunodeficiency virus). A public policy topic is whether anencephalic babies should be used as organ donors.Annas ... Author, Article, and Disclosure InformationAffiliations: University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byError humano, seguridad del paciente y formación en medicina 1 March 1994Volume 120, Issue 5Page: 448KeywordsAdolescentsBioethicsBirthContraceptivesDrugsHIVPublic policy ePublished: 15 August 2000 Issue Published: 1 March 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Body surface mapping of ectopic left and right ventricular activation. QRS spectrum in patients without structural heart disease.
Authors: A SippensGroenewegen, H Spekhorst, N M van Hemel, J H Kingma, R N Hauer, M J Janse, A J Dunning
Journal: Circulation (1990)

The value of simultaneous 62-lead electrocardiographic recordings in localizing the site of origin of ectopic ventricular activation in a structurally normal heart was assessed by examining body surface QRS integral maps in 12 patients during left and right ventricular (LV and RV) pacing at 182 distinct endocardial sites. A data base of 38 characteristic mean integral maps was composed after visually selecting subgroups with nearly identical total QRS integral morphology and numerically evaluating intrasubgroup pattern uniformity and intersubgroup pattern variability. Corresponding endocardial pacing site locations were computed by a biplane cineradiographic method and outlined as segments on a standardized LV and RV polar projection. LV pacing resulted in 25 markedly different mean total QRS integral patterns, showing higher electrocardiographic sensitivity for anteroseptal (18 patterns) compared with posterolateral regions (seven patterns). RV pacing demonstrated 13 mean total QRS integral patterns, exhibiting less intersubgroup variation and comparatively low electrocardiographic sensitivity for the basal anterior and outflow regions. Comparison of LV with RV pacing revealed that QRS configurations produced at LV apical and LV midseptal sites closely resembled QRS configurations generated at RV apical, RV septal, and RV anterior sites, respectively. Total QRS time integral amplitudes showed considerable intrasubgroup variation but permitted global differentiation of spatially similar QRS patterns obtained during pacing at LV and RV sites. This study demonstrates that the QRS pattern of the total body surface electrocardiogram allows discrimination among 38 different LV and RV segments of ectopic endocardial impulse formation in patients with normal cardiac anatomy.
National Trends in Patient Safety for Four Common Conditions, 2005–2011
Authors: Yun Wang, Noel Eldridge, Mark L. Metersky, Nancy R. Verzier, Thomas P. Meehan, Michelle M. Pandolfi, JoAnne M. Foody, Shih-Yieh Ho, Deron Galusha, Rebecca E. Kliman, Nancy Sonnenfeld, Harlan M. Krumholz, James Battles
Journal: New England Journal of Medicine (2014)

Changes in adverse-event rates among Medicare patients with common medical conditions and conditions requiring surgery remain largely unknown.We used Medicare Patient Safety Monitoring System data abstracted from medical records on 21 adverse events in patients hospitalized in the United States between 2005 and 2011 for acute myocardial infarction, congestive heart failure, pneumonia, or conditions requiring surgery. We estimated trends in the rate of occurrence of adverse events for which patients were at risk, the proportion of patients with one or more adverse events, and the number of adverse events per 1000 hospitalizations.The study included 61,523 patients hospitalized for acute myocardial infarction (19%), congestive heart failure (25%), pneumonia (30%), and conditions requiring surgery (27%). From 2005 through 2011, among patients with acute myocardial infarction, the rate of occurrence of adverse events declined from 5.0% to 3.7% (difference, 1.3 percentage points; 95% confidence interval [CI], 0.7 to 1.9), the proportion of patients with one or more adverse events declined from 26.0% to 19.4% (difference, 6.6 percentage points; 95% CI, 3.3 to 10.2), and the number of adverse events per 1000 hospitalizations declined from 401.9 to 262.2 (difference, 139.7; 95% CI, 90.6 to 189.0). Among patients with congestive heart failure, the rate of occurrence of adverse events declined from 3.7% to 2.7% (difference, 1.0 percentage points; 95% CI, 0.5 to 1.4), the proportion of patients with one or more adverse events declined from 17.5% to 14.2% (difference, 3.3 percentage points; 95% CI, 1.0 to 5.5), and the number of adverse events per 1000 hospitalizations declined from 235.2 to 166.9 (difference, 68.3; 95% CI, 39.9 to 96.7). Patients with pneumonia and those with conditions requiring surgery had no significant declines in adverse-event rates.From 2005 through 2011, adverse-event rates declined substantially among patients hospitalized for acute myocardial infarction or congestive heart failure but not among those hospitalized for pneumonia or conditions requiring surgery. (Funded by the Agency for Healthcare Research and Quality and others.).
US panel asks for sea change in peptic ulcer therapy
Authors: F B Charatan
Journal: BMJ (1994)

Peptic ulcers should be treated by a combination of acid reducing drugs and antimicrobial therapy, said a 14 member consensus panel convened by the National Institutes of Health in the United States last week. The panel confirmed a strong causal link between infection with Helicobacter pylori and peptic ulcers and gastritis. No evidence was found for a link between H pylori infection and “non-ulcer dyspepsia.”

* Everyone will have health care but how much will it cost?

(Fig Omitted)

The panel concluded …
Linear IgA bullous dermatosis of adults and children: an immunoelectron microscopic study
Authors: B. BHOGAL, FENELLA WOJNAROWSKA, R.A. MARSDEN, A. DAS, M.M. BLACK, P.H. MCKEE
Journal: British Journal of Dermatology (1987)

The ultrastructural localization of the IgA deposits in the skin of 15 patients with linear IgA bullous dermatosis of adults (LAD), 13 with chronic bullous dermatosis of childhood (CBDC) and three with childhood cicatricial pemphigoid (CCP) were studied. The site of the antigen was determined using sera from two LAD, 13 CBDC and two CCP patients. In all 31 patients the IgA was located predominantly below the lamina lucida (sublamina densa). Similarly, the indirect immunoelectron microscopic studies demonstrated the antigen to be present at the same site, below the lamina densa. This suggests that in linear IgA bullous dermatosis the antibody reacts with the antigen in the sublamina densa region of the basement membrane zone.
Gene-environment interaction influences the reactivity of autoantibodies to citrullinated antigens in rheumatoid arthritis
Authors: Diane van der Woude, Wendimagegn Ghidey Alemayehu, Willem Verduijn, René R P de Vries, Jeanine J Houwing-Duistermaat, Tom W J Huizinga, René E M Toes
Journal: Nature Genetics (2010)
Activin and transforming growth factor-β signaling pathways are activated after allergen challenge in mild asthma
Authors: Harsha H. Kariyawasam, Sophie Pegorier, Julia Barkans, Georgina Xanthou, Maxine Aizen, Sun Ying, A. Barry Kay, Clare M. Lloyd, Douglas S. Robinson
Journal: Journal of Allergy and Clinical Immunology (2009)
Novel Recombinant Human B7-H4 Antibodies Overcome Tumoral Immune Escape to Potentiate T-Cell Antitumor Responses
Authors: Denarda Dangaj, Evripidis Lanitis, Aizhi Zhao, Shree Joshi, Yi Cheng, Raphael Sandaltzopoulos, Hyun-Jeong Ra, Gwenn Danet-Desnoyers, Daniel J. Powell, Nathalie Scholler
Journal: Cancer Research (2013)

B7-H4 (VTCN1, B7x, B7s) is a ligand for inhibitory coreceptors on T cells implicated in antigenic tolerization. B7-H4 is expressed by tumor cells and tumor-associated macrophages (TAM), but its potential contributions to tumoral immune escape and therapeutic targeting have been less studied. To interrogate B7-H4 expression on tumor cells, we analyzed fresh primary ovarian cancer cells collected from patient ascites and solid tumors, and established cell lines before and after in vivo passaging. B7-H4 expression was detected on the surface of all fresh primary human tumors and tumor xenotransplants, but not on most established cell lines, and B7-H4 was lost rapidly by tumor xenograft cells after short-term in vitro culture. These results indicated an in vivo requirement for B7-H4 induction and defined conditions for targeting studies. To generate anti-B7-H4-targeting reagents, we isolated antibodies by differential cell screening of a yeast-display single-chain fragments variable (scFv) library derived from patients with ovarian cancer. We identified anti-B7-H4 scFv that reversed in vitro inhibition of CD3-stimulated T cells by B7-H4 protein. Notably, these reagents rescued tumor antigen-specific T-cell activation, which was otherwise inhibited by coculture with antigen-loaded B7-H4+ APCs, B7-H4+ tumor cells, or B7-H4- tumor cells mixed with B7-H4+ TAMs; peritoneal administration of anti-B7-H4 scFv delayed the growth of established tumors. Together, our findings showed that cell surface expression of B7-H4 occurs only in tumors in vivo and that antibody binding of B7-H4 could restore antitumor T-cell responses. We suggest that blocking of B7-H4/B7-H4 ligand interactions may represent a feasible therapeutic strategy for ovarian cancer.
Scientific Literacy and the Myth of the Scientific Method
Authors: Fred R. Abrams
Journal: JAMA (1993)

I would not describe this expository book by Bauer as a page turner, eagerly absorbed in one or two sittings. Nevertheless, it does fulfill its stated purpose, illustrating that a holistic view of science, technology, and society (the author abbreviates it STS) is necessary and useful to evaluate the place of science and technology in modern life. Regarding scientific literacy, the proverb of American humorist Josh Billings might epitomize Bauer's viewpoint: "It is better to know nothing than to know what ain't so." The author notes that anyone's literacy is only measured by the degree to which it reflects current dogma; that itself is not cast in stone. As for science guiding humankind to the solution of age-old problems, that fond hope has been confounded by the fact that the practice of science is a human endeavor. Rather than change our behavior, we prefer to suppress knowledge that would lead
Short term effects of indomethacin on rat small intestinal permeability. Role of eicosanoids and platelet activating factor.
Authors: F Mion, J C Cuber, Y Minaire, J A Chayvialle
Journal: Gut (1994)

Short term effects of indomethacin on intestinal permeability were studied on a model of rat isolated vascularly perfused terminal ileum. The objectives of this study were (a) to assess the effects of indomethacin on intestinal permeability and histology; (b) to assess the effects of prostaglandins, leukotrienes, and platelet activating factor (PAF) on the same parameters; (c) to evaluate the role of these inflammation mediators on indomethacin induced permeability modifications. Intravascular administration of 1.25 and 2.5 mM indomethacin induced a significant increase of 51Cr-EDTA transfer rate. Histological analysis showed only mucosal oedema. Pretreatment with 16,16 dimethyl-prostaglandin E2 did not reverse these changes. Intravascular administration of PAF, leukotrienes B4 and D4 provoked a significant rise in 51Cr-EDTA transfer rate and intraluminal protein leakage, with an intense vascocongestion of the mucosal capillaries. These changes were completely prevented by perfusion of the respective specific antagonists (BN52021 for PAF, LY255,583 for leukotriene B4 and MK571 for leukotriene D4). None of these three antagonists, however, or MK886, a selective 59-lipo-oxygenase inhibitor, could reverse the indomethacin induced permeability changes. Indomethacin induced increased intestinal permeability at these high concentrations does not seem to be a result of changed prostanoid or PAF metabolism. Alternative mechanisms of the initial damage of non-steroid anti-inflammatory drugs should be sought.
Suppression of experimental crescentic glomerulonephritis by interleukin-10 gene transfer
Authors: Adel G.A. El-Shemi, Hidehiko Fujinaka, Asako Matsuki, Junichi Kamiie, Pavel Kovalenko, Zhenyun Qu, Vladimir Bilim, Goro Nishimoto, Eishin Yaoita, Yuatka Yoshida, Ignacio Anegon, Tadashi Yamamoto
Journal: Kidney International (2004)
Histopathological correlates of basal cell carcinoma in the slice and en face imaging modes of high-definition optical coherence tomography
Authors: T. Gambichler, I. Plura, P. Kampilafkos, K. Valavanis, M. Sand, F.G. Bechara, M. Stücker
Journal: British Journal of Dermatology (2013)

High-definition optical coherence tomography (HD-OCT) scanners have recently been developed, providing significantly higher resolution than conventional OCT.To assess the relationship between recently defined histopathological HD-OCT correlates of basal cell carcinomas (BCC) and possible predictors for the most common tumour subtypes.For HD-OCT imaging, we used the Skintell(®) device. Twenty-five BCCs were histopathologically confirmed (including both vertical and horizontal haematoxylin and eosin and Alcian blue sectioning) and correlated with HD-OCT images.In the en face mode, lobulated nodules were seen in 21/25 BCCs (84%), peripheral rimming in 18/25 (72%), epidermal disarray in 18/25 (72%) and variably refractile stroma in 22/25 (88%). In the slice imaging mode, we observed destruction of layering in 19/25 (76%) BCCs. In both the slice and en face modes a significant correlation was observed between peritumoral rimming and grey/dark oval structures and lobulated nodules. Alcian blue stains showed peritumoral mucin deposits correlating with peripheral rimming around the tumour nodules. In a logistic regression model, we did not observe significant independent micromorphological HD-OCT predictors for either the solid or superficial BCC subtypes.In agreement with recent studies we have demonstrated that HD-OCT using the slice and en face imaging modes can visualize histopathological correlates of BCC, and potentially aid noninvasive diagnostics. However, using HD-OCT correlation it was not possible to predict the superficial or solid BCC subtypes. For the first time we have shown that peripheral rimming in HD-OCT correlates with peritumoral mucin deposition.