tbuckley/cabot-search huggingface dataset:
Nimodipine, a Centrally Active Calcium Antagonist, Exerts a Beneficial Effect on Contrast Sensitivity in Patients with Normal-tension Glaucoma and in Control Subjects
Authors: Swaraj Bose, Jody R. Piltz, Michael E. Breton
Journal: Ophthalmology (1995)

Background/Purpose: The use of calcium antagonists in patients with normaltension glaucoma (NTG) currently is under investigation.The aim of this study is to evaluate the effect of an acute dose of oral nimodipine, a centrally active calcium antagonist, on spatial contrast sensitivity in patients with NTG and in age-matched control subjects.Methods: Spatial contrast sensitivity was measured using the Pelli-Robson and the Vistech 6000 charts in 14 patients with NTG and in 17 control subjects.Testing was performed at baseline and at two subsequent sessions.Measurements were recorded 2 hours after oral administration of either nimodipine or placebo in a randomized, double-masked manner.Data were analyzed using unpaired, two-tailed Student's t test for between-group comparisons and repeated measures analysis of variance for withingroup comparisons.Results: Using the Pelli-Robson charts, baseline contrast sensitivity was significantly lower in patients with NTG compared with control subjects (P < 0.05, unpaired Student's t test).There was a significant increase in log contrast sensitivity after administration of nimodipine compared with baseline and placebo in patients with NTG (baseline, 1.39 ± 0.38; placebo, 1.41 ± 0.40; nimodipine, 1.51 ± 0.39) and in control subjects (baseline, 1.62 ± 0.11; placebo, 1.64 ± 0.10; nimodipine, 1.81 ± 0.14) (P < 0.05, repeated measures analysis of variance).A similar trend was observed using the Vistech charts. Conclusion:These results suggest that central visual function as measured by Pelli-Robson and Vistech contrast sensitivity is impaired in eyes with NTG.An acute, oral administration of nimodipine, a calcium antagonist, improved contrast sensitivity in patients with NTG and in control subjects.The mechanism of this improvement is not fully understood.Further studies are needed to evaluate the effect of long-term administration in glaucoma.
THE IMPACT OF TRANSRADIAL APPROACH FOR IN-HOSPITAL MAJOR BLEEDING IN NON-ST ELEVATION ACUTE CORONARY SYNDROME PATIENTS AT MODERATE TO VERY HIGH CRUSADE BLEEDING SCORES
Authors: Keun-Ho Park, Myung Ho Jeong, Youngkeun Ahn, Won Yu Kang, Kwang Soo Cha, Min Soo Hyon, Byung Ok Kim, Moo Hyun Kim, Kyoo Rok Han, Junghan Yoon
Journal: Journal of the American College of Cardiology (2012)
Divergent Structures of Caenorhabditis elegans Cytochrome P450 Genes Suggest the Frequent Loss and Gain of Introns During the Evolution of Nematodes
Authors: O. Gotoh
Journal: Molecular Biology and Evolution (1998)

The Caenorhabditis elegans genome contains more than 60 cytochrome P450 (CYP) genes. The exon-intron organizations of all of the available and potentially active C. elegans CYP genes were inferred by a newly developed program for predicting protein-coding exons based on the alignment of a genomic DNA sequence and a protein profile. From the predicted amino acid sequences, all of the C. elegans CYP genes except one were classified into three groups, which were closely related to the mammalian drug-metabolizing P450 gene families CYP2, CYP3, and CYP4. The gene structures were strikingly divergent within each group; 20, 10, and 5 unique gene organizations were identified among 40, 18, and 5 genes in the CYP2-, CYP3-, and CYP4-related groups, respectively. The degrees of divergence in gene organization were strongly correlated with those in the amino acid sequences of encoding proteins, and the minimum rate of change in an intron insertion site was estimated to be about 90 times less frequent than amino acid substitutions. Parsimonious analyses suggested that frequent loss and gain of introns has occurred during the evolution of CYP genes in each group after the divergence of nematodes, arthropods, and deuterostomia. Few, if any, incidents of intron sliding were evident, and a model that did not allow intron insertions was highly inconsistent with the observations. All of these findings are explained better by the intron-late view than by the intron-early view.
Medical Schools and the Delivery of Medical Care to the Community
Authors: Paul M. Densen
Journal: New England Journal of Medicine (1971)

The increasing number of medical centers involved in collaborative and innovative health services in the community is but one reflection of social concerns and pressures for change in the health-care system. Medical schools and their affiliated teaching hospitals are trying in various ways to adapt their teaching, research and service functions to these concerns.With the intention of exploring how a number of medical centers are approaching these problems, the Harvard Center for Community Health and Medical Care sponsored an Invitational Conference on the Evaluation of University Medical Care Programs. These programs included Columbia Medical Care Plan and East Baltimore . . .
Protective effect of mesenchymal stem cells (MSC) on hypoxia-induced epithelial-mesenchymal transition of alveolar epithelial cells (AEC)
Authors: Yurdagul Uzunhan, Nadia Randrianarison, Dominique Marchant, Nicolas Dard, Jerôme Larghero, Carole Planès
Journal: European Respiratory Journal (2012)

Background: Epithelial-to-mesenchymal transition (EMT) of AEC induced by TGF-β1 or hypoxia (HX) may contribute to pulmonary fibrosis. In animal models of lung fibrosis, administration of allogenic MSC reduced fibrosis and mortality by an unknown mechanism. We hypothesized that MSC may favor alveolar wound healing by preventing hypoxia-induced EMT. We tested in vitro the paracrine effects of MSC on the phenotypic changes of AEC induced by HX.

Methods: Rat AEC cultured on Transwell filters were exposed to HX (3 or 1.5% O2) for up to 12 days in the presence/absence of human MSC on the bottom of the well. Transepithelial electrical resistance (TER) as well as epithelial markers (E-cadherin, ZO-1, TTF-1) and mesenchymal markers (smooth muscle α-actine, vimentin) were assessed by ohm-meter, immunofluorescence and Western blot at d6 and d12.

Results: Exposure of AEC to HX resulted in a dose- and time-dependent decrease of TER and of epithelial marker expression, together with an increase in mesenchymal marker expression. These effects were reproduced by treatment with cobalt chloride and were partially prevented by anti-oxydant drugs (Euk134 or N-acetyl-cystein). Co-culture with MSC (or MSC-conditioned medium) partially prevented the effects of HX regarding TER and phenotypic changes.

Conclusion: These results indicate that MSC alleviate the phenotypic changes of AEC induced by HX in vitro through a paracrine mechanism. Preservation of AEC phenotype by MSC may limit EMT and could partly explain the anti-fibrotic effect of MSC in vivo.

Funded by: College des Enseignants de Pneumologie, Chancellerie des Universites de Paris (Fondation du Legs Poix).
Significance of Bronchoalveolar Lavage for the Diagnosis of Idiopathic Pulmonary Fibrosis
Authors: Shinichiro Ohshimo, Francesco Bonella, Ai Cui, Martin Beume, Nobuoki Kohno, Josune Guzman, Ulrich Costabel
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

According to the 2002 ATS/ERS Consensus Classification, a confident diagnosis of idiopathic pulmonary fibrosis (IPF) without surgical lung biopsy is made with consistent clinical/physiological findings and the typical features on high-resolution computed tomography (HRCT). Bronchoalveolar lavage (BAL) and/or transbronchial biopsy, one of four major criteria in the 2000 ATS/ERS IPF Statement, was no more essential in the diagnostic algorithm of 2002 ATS/ERS Consensus Classification.To evaluate the additional utility of BAL for the diagnosis of IPF.A total of 101 patients with suspected IPF on HRCT were studied. Twenty-seven patients were excluded because of lack of functional impairment (n = 20), an underlying condition causing fibrosis (n = 5), or a clinical history inconsistent with IPF (n = 2). The remaining 74 patients met all the criteria recommended in the 2002 ATS/ERS Consensus Classification for making a diagnosis in the absence of surgical biopsy. The final diagnosis was made with further examinations, including pathological analysis, in patients who showed inconsistent findings for IPF on BAL.A cut-off level of 30% for lymphocytes in BAL demonstrated a favorable discriminative power for the diagnosis of IPF. Six of the 74 patients (8%) showed a lymphocytosis of 30% or greater in BAL. Their final diagnoses were idiopathic nonspecific interstitial pneumonia (n = 3) and extrinsic allergic alveolitis (n = 3). The change in perception of the diagnosis was validated by a surgical biopsy in two cases and by subsequent outcome in four cases.BAL lymphocytosis changed the diagnostic perception in six of 74 patients who would have been misdiagnosed as having IPF without BAL.
Air Versus Water
Authors: J. David Baxter
Journal: Annals of Internal Medicine (2010)

On Being a Doctor2 November 2010Air Versus WaterJ. David Baxter, MDJ. David Baxter, MDFrom Memorial University Medical Center, Savannah, GA 31404.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-9-201011020-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Seeing her again lying there brought tears to my eyes. My wife's beautiful mother, a retired operating room nurse, was slowly dying of Alzheimer's disease, as she had been for the past 10 years. Initially she had been just forgetful and (we thought) merely stressed, but as time went by, her confusion and forgetfulness led us to seek a physician. After consultations, laboratory tests, and scans, we learned the cruel diagnosis and our fears had been confirmed. With reluctance, we slowly accepted her diagnosis, even though my father-in-law would describe her condition in the early days as only a “touch” ... Author, Article, and Disclosure InformationAffiliations: From Memorial University Medical Center, Savannah, GA 31404.Corresponding Author: J. David Baxter, MD, Memorial University Medical Center, 1101 Lexington Avenue, Savannah, GA 31404; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byArtificial Nutrition and Hydration: The Evolution of Ethics, Evidence, and Policy 2 November 2010Volume 153, Issue 9Page: 616-617KeywordsAlzheimer diseaseDementiaFearNursesNutritionProgressive diseasesRespiratory failureStarvationTouchVentilators ePublished: 2 November 2010 Issue Published: 2 November 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
III. THE RIBONUCLEASES OF HUMAN EPIDERMIS
Authors: SUSANNE W. MELBYE, BARBARA A. BRANT, IRWIN M. FREEDBERG
Journal: British Journal of Dermatology (1977)

Sodium acetate and sulphuric acid extracts of human epidermis can each be separated by chromatographic techniques into three or more fractions with ribonuclease activity. Eight of these fractions were compared with respect to molecular weight, pH activity profile, polyribonucleotide hydrolysis, and activity in the presence of low levels of spermidine. Sodium acetate and sulphuric acid extracts were also prepared from callus and from psoriatic lesions and compared with extracts from normal epidermis for their response to exogenous spermidine. All eight human epidermal ribonuclease fractions studied had an apparent molecular weight of 15,000 daltons. Seven of the ribonuclease fractions were optimally active at alkaline pHs (pH 7.3–7.6 in sodium phosphate and pH 81.in Tris‐HCl) while the eighth ribonuclease was most active at pH 5.6 in a citrate‐phosphate buffer. All enzymes hydrolyzed polycytidylic acid and five also hydrolyzed polyuridylic add. None hydrolyzed polyadenylic acid. Seven of the eight ribonucleases studied exhibited greater activity in the presence of added spermidine. The extracts from psoriatic scales showed markedly elevated ribonuclease levels which could not be raised further by the addition of spermidine.
Smoking and death: the past 40 years and the next 40
Authors: R Peto
Journal: BMJ (1994)

between 1992 and 1993 (P < 0 05) in the north of England, where Reg was prominent, and remained stable at 7% in the south, where he did not appear.This change could, of course, be due to other factors, but it is not unlikely that the Regal campaign made a substantial contribution to this apparent increase.In view of these findings the Advertising Standards Authority's decision to withdraw the Reg campaign would seem appropriate.We thank the respondents and schools for their cooperation, all the researchers for their hard work, and the Health Education Authority for its support and encouragement.1 Smee C for House of
Creatine kinase knockout mice show left ventricular hypertrophy and dilatation, but unaltered remodeling post-myocardial infarction
Authors: M NAHRENDORF, M SPINDLER, K HU, L BAUER, O RITTER, P NORDBECK, T QUASCHNING, K HILLER, J WALLIS, G ERTL
Journal: Cardiovascular Research (2004)

Objective: Creatine kinase (CK) is responsible for the transport of high-energy phosphates in excitable tissue and is of central importance in myocardial energy homeostasis. Significant changes in myocardial energetics have been reported in mice lacking the various CK isoenzymes. Our hypothesis was that ablation of CK isoenzymes leads to cardiac hypertrophy, impaired function, and aggravation of left ventricular remodeling post-myocardial infarction.
Abstract 1048: Dichotomy effects of Akt signaling in breast cancer
Authors: Huey-Jen L. Lin, Zhengang Peng
Journal: Cancer Research (2014)

Abstract Background: The oncogenic roles contributed by the Akt/PKB kinase family remain controversial and presumably depend on cell context, but are perceived to be modulated by an interplay and net balance between various isoforms. This study is intended to decipher whether distinct Akt kinase isoforms exert either redundant or unique functions in regulating neoplastic features of breast cancer cells, including epithelial-mesenchymal transition (EMT), cell motility, and stem/progenitor cell expansion. Results: We demonstrate that overactivation of Akt signaling in nonmalignant MCF10A cells and in primary cultures of normal human mammary epithelial tissue results in previously unreported inhibitory effects on EMT, cell motility and stem/progenitor cell expansion. Importantly, this effect is largely redundant and independent of Akt isoform types. However, using a series of isogenic cell lines derived from MCF-10A cells but exhibiting varying stages of progressive tumorigenesis, we observe that this inhibition of neoplastic behavior can be reversed in epithelial cells that have advanced to a highly malignant state. In contrast to the tumor suppressive properties of Akt, activated Akt signaling in MCF10A cells can rescue cell viability upon treatment with cytotoxic agents. This feature is regarded as tumor-promoting. Conclusion: We demonstrate that Akt signaling conveys novel dichotomy effects in which its oncogenic properties contributes mainly to sustaining cell viability, as opposed to the its tumor suppressing effects, which are mediated by repressing EMT, cell motility, and stem/progenitor cell expansion. While the former exerts a tumor-enhancing effect, the latter merely acts as a safeguard by restraining epithelial cells at the primary sites until metastatic spread can be moved forward, a process that is presumably dictated by the permissive tumor microenvironment or additional oncogenic insults. Citation Format: Huey-Jen L. Lin, Zhengang Peng. Dichotomy effects of Akt signaling in breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1048. doi:10.1158/1538-7445.AM2014-1048
Veterans Affairs Initiative to Prevent Methicillin-Resistant<i>Staphylococcus aureus</i>Infections
Authors: Rajiv Jain, Stephen M. Kralovic, Martin E. Evans, Meredith Ambrose, Loretta A. Simbartl, D. Scott Obrosky, Marta L. Render, Ron W. Freyberg, John A. Jernigan, Robert R. Muder, LaToya J. Miller, Gary A. Roselle
Journal: New England Journal of Medicine (2011)

Health care-associated infections with methicillin-resistant Staphylococcus aureus (MRSA) have been an increasing concern in Veterans Affairs (VA) hospitals.A "MRSA bundle" was implemented in 2007 in acute care VA hospitals nationwide in an effort to decrease health care-associated infections with MRSA. The bundle consisted of universal nasal surveillance for MRSA, contact precautions for patients colonized or infected with MRSA, hand hygiene, and a change in the institutional culture whereby infection control would become the responsibility of everyone who had contact with patients. Each month, personnel at each facility entered into a central database aggregate data on adherence to surveillance practice, the prevalence of MRSA colonization or infection, and health care-associated transmissions of and infections with MRSA. We assessed the effect of the MRSA bundle on health care-associated MRSA infections.From October 2007, when the bundle was fully implemented, through June 2010, there were 1,934,598 admissions to or transfers or discharges from intensive care units (ICUs) and non-ICUs (ICUs, 365,139; non-ICUs, 1,569,459) and 8,318,675 patient-days (ICUs, 1,312,840; and non-ICUs, 7,005,835). During this period, the percentage of patients who were screened at admission increased from 82% to 96%, and the percentage who were screened at transfer or discharge increased from 72% to 93%. The mean (±SD) prevalence of MRSA colonization or infection at the time of hospital admission was 13.6±3.7%. The rates of health care-associated MRSA infections in ICUs had not changed in the 2 years before October 2007 (P=0.50 for trend) but declined with implementation of the bundle, from 1.64 infections per 1000 patient-days in October 2007 to 0.62 per 1000 patient-days in June 2010, a decrease of 62% (P<0.001 for trend). During this same period, the rates of health care-associated MRSA infections in non-ICUs fell from 0.47 per 1000 patient-days to 0.26 per 1000 patient-days, a decrease of 45% (P<0.001 for trend).A program of universal surveillance, contact precautions, hand hygiene, and institutional culture change was associated with a decrease in health care-associated transmissions of and infections with MRSA in a large health care system.
Lecture Notes on Ophthalmology
Authors: David Shoch
Journal: JAMA (1960)

A remarkable amount of material has been compressed into this short textbook. It is astonishing to find that almost any subject that occurs to the reader is covered somewhere in this book. If there is any criticism to be made, it is that perhaps some things have been included which are outside the scope of such a book. For example, the illustration of the technique of recession of the medial rectus hardly gives the senior medical student an appreciation of the technique involved in this procedure. A similar objection can be made to the illustrations on cataract extraction and trephine operation for glaucoma. Finally, the illustrations for thyrotropic exophthalmos and of enucleation of the eye are straight out of "Grand Guignol." They undoubtedly have great dramatic value, but they are enough to frighten even the hardened ophthalmologist, let alone the poor senior medical student. These are minor objections and, all
Hepatitis C virus entry: Molecular biology and clinical implications
Authors: Heidi Barth, Jake T. Liang, Thomas F. Baumert
Journal: Hepatology (2006)

With an estimated 170 million infected individuals, hepatitis C virus (HCV) has a major impact on public health. A vaccine protecting against HCV infection is not available, and current antiviral therapies are characterized by limited efficacy, high costs, and substantial side effects. Binding of the virus to the cell surface followed by viral entry is the first step in a cascade of interactions between virus and the target cell that is required for the initiation of infection. Because this step represents a critical determinant of tissue tropism and pathogenesis, it is a major target for host cell responses such as antibody-mediated virus-neutralization-and a promising target for new antiviral therapy. The recent development of novel tissue culture model systems for the study of the first steps of HCV infection has allowed rapid progress in the understanding of the molecular mechanisms of HCV binding and entry. This review summarizes the impact of recently identified viral and host cell factors for HCV attachment and entry. Clinical implications of this important process for the pathogenesis of HCV infection and novel therapeutic interventions are discussed.
Recruiting patients to medical research: double blind randomised trial of “opt-in” versus “opt-out” strategies
Authors: Cornelia Junghans, Gene Feder, Harry Hemingway, Adam Timmis, Melvyn Jones
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b>To evaluate the effect of opt-in compared with opt-out recruitment strategies on response rate and selection bias. <b>Design</b>Double blind randomised controlled trial. <b>Setting</b>Two general practices in England. <b>Participants</b>510 patients with angina. <b>Intervention</b>Patients were randomly allocated to an opt-in (asked to actively signal willingness to participate in research) or opt-out (contacted repeatedly unless they signalled unwillingness to participate) approach for recruitment to an observational prognostic study of patients with angina. <b>Main outcome measures</b>Recruitment rate and clinical characteristics of patients. <b>Results</b> The recruitment rate, defined by clinic attendance, was 38% (96/252) in the opt-in arm and 50% (128/258) in the opt-out arm (P = 0.014). Once an appointment had been made, non-attendance at the clinic was similar (20% opt-in arm <i>v</i> 17% opt-out arm; P = 0.86). Patients in the opt-in arm had fewer risk factors (44% <i>v</i> 60%; P = 0.053), less treatment for angina (69% <i>v</i> 82%; P = 0.010), and less functional impairment (9% <i>v</i> 20%; P = 0.023) than patients in the opt-out arm. <b>Conclusions</b> The opt-in approach to participant recruitment, increasingly required by ethics committees, resulted in lower response rates and a biased sample. We propose that the opt-out approach should be the default recruitment strategy for studies with low risk to participants.
Hospital-bed deaths, injuries force down-switch modifications
Authors: Beverly Merz
Journal: JAMA (1983)

Gregory Davis, hospitalized for hypoglycemia in Oak Lawn, Ill, was merely exercising the native curiosity of an 11-year-old boy. He wanted to know what made his bed go up and down so he punched the switch that lowered the steel frame, then crawled under the bed to watch it descend. It came down fast. Within 15 seconds, Gregory was trapped between the frame and the pedestal base. Within an hour he was dead, his neck crushed. Gregory's death, on April 17, was the third such hospital bed fatality in 15 months. In October 1982, a 6-year-old Toronto boy, similarly trapped, died of skull fractures. The previous January in Zeeland, Mich, a 3-year-old girl who had taken refuge under a bed in a game of "hide-and-seek" was killed after apparently activating the down control by accident. The beds involved were virtually identical in design. All were pedestal-style electric beds; all featured