tbuckley/cabot-search huggingface dataset:
Keratin 19 demonstration of canal of hering loss in primary biliary cirrhosis: “Minimal Change PBC”?
Authors: Fahad M. Khan, Arathi Rajendra Komarla, Paulo G. Mendoza, Henry C. Bodenheimer, Neil D. Theise
Journal: Hepatology (2012)

Liver biopsy is important for diagnosing primary biliary cirrhosis (PBC). Prior investigations suggest that immunostaining for biliary keratin 19 (K19) may show the earliest changes suspicious for PBC, namely, loss of the canals of Hering (CoH). We aimed to study the clinical outcomes of patients whose biopsy specimens appeared histologically near normal or with minimal inflammatory changes, but in which K19 staining revealed widespread periportal CoH loss, a finding we termed "minimal change PBC." Ten patients were identified prospectively as having nearly normal or mildly inflamed biopsy specimens without diagnostic or suggestive histologic features of PBC, but with near complete CoH loss; six had available follow-up clinical data, one had follow-up biopsy. Controls for clinical and/or K19 analysis included six normal livers and biopsy specimens from 10 patients with confirmed early PBC, 10 with early stage chronic hepatitis C (CHC), and nine with resolving, self-limited hepatitis (RSLH). Staining for K19 in normal controls, livers with "minimal change" PBC, CHC, and RSLH showed 9.2 ± 6.0, 0.44 ± 0.37 (P < 0.0001), 5.7 ± 4.6 (n.s.), 4.1 ± 2.1 (P < 0.02) CoH per portal tract, respectively. Patients with available clinical follow up, compared to patients with diagnostic early-stage PBC biopsies, showed identical treatment responses to ursodeoxycholic acid, similar rates and types of nonhepatic autoimmune diseases, and/or subsequent development of autoimmune hepatitis overlap syndrome.We suggest that CoH loss demonstrated by K19 immunostaining is an early feature in PBC. Clinical findings in the years following biopsy, including response to ursodeoxycholic acid, show identical changes to patients with biopsy confirmed PBC. We suggest that this "minimal change" feature may support a clinical diagnosis of PBC even in the absence of characteristic, granulomatous, duct destructive lesions.
Development and validation of the self-administered Food Allergy Quality of Life Questionnaire for adolescents
Authors: Bertine M.J. Flokstra-de Blok, Audrey DunnGalvin, Berber J. Vlieg-Boerstra, Joanne N.G. Oude Elberink, Eric J. Duiverman, Jonathan O'Brien Hourihane, Anthony E.J. Dubois
Journal: Journal of Allergy and Clinical Immunology (2008)
Virulence factors in the colonization and persistence of bacteria in the airways.
Authors: L van Alphen, H M Jansen, J Dankert
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa are commonly isolated from sputum specimens of patients with lower respiratory tract infections. Haemophilus influenzae, S. pneumoniae, and M. catarrhalis have several pathogenic properties in common. These bacteria are able to interact with mucus, to exert ciliotoxic activity, to adhere to bronchial epithelial cells, and to invade airway epithelium. Haemophilus influenzae and S. pneumoniae strains persist for many months in the respiratory tract of patients with chronic obstructive pulmonary disease (COPD), despite the specific antibodies present in serum and sputum against the persistent strain. Especially during exacerbations persistent strains with changes in their antigenic composition are isolated. Among H. influenzae strains, the antigenic characteristics of the outer membrane protein composition vary. Variation in S. pneumoniae occurs in capsular polysaccharides, the major immunogens of this bacterium. Such variations affect the efficacy of the antibody-mediated defense mechanisms against the bacteria. Between exacerbations, particularly H. influenzae, S. pneumoniae strains are recovered from the sputum of patients with COPD. Recovery may continue for periods up to 2 yr, although not continuously. Besides ineffective antibody-mediated defense mechanisms, it is likely that hiding of the bacteria in tissue contributes to the persistence of these bacteria in patients with COPD.
Growth–Factor Independence of A New Differentiated Hepatitis B Virus Dna–Negative Human Hepatoma Cell Line
Authors: Patrizia Bagnarelli, Giulia Devescovi, Aldo Manzin, Italo Bearzi, Patrizia Bonazzi, Guido Carloni, Massimo Clementi
Journal: Hepatology (1990)

The establishment of a new, differentiated, hepatitis B virus DNA-negative, human hepatoma cell line (named PLC/AN/2) is described. Neoplastic liver tissue was obtained during hepatectomy in an HBsAg-negative man. The established cell line is negative for alpha-fetoprotein and carcinoembryonic antigen; it has retained in vitro some of the differentiated functions of normal hepatocytes. Additionally, it presents a distinctive rearrangement (translocation) at the long arm of chromosome 4. The high degree of independence from serum growth factor requirements appears to be a major in vitro characteristic of PLC/AN/2 cells, making them a suitable model system for the more precise definition of the human hepatocellular carcinoma phenotype, including mechanisms of growth control.
Positron Emission Tomography Imaging with 18F-Labeled Z<i>HER2:2891</i> Affibody for Detection of HER2 Expression and Pharmacodynamic Response to HER2-Modulating Therapies
Authors: Sebastian Trousil, Susan Hoppmann, Quang-Dé Nguyen, Maciej Kaliszczak, Giampaolo Tomasi, Peter Iveson, Duncan Hiscock, Eric O. Aboagye
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Expression of HER2 has profound implications on treatment strategies in various types of cancer. We investigated the specificity of radiolabeled HER2-targeting ZHER2:2891 Affibody, [18F]GE-226, for positron emission tomography (PET) imaging. Experimental Design: Intrinsic cellular [18F]GE-226 uptake and tumor-specific tracer binding were assessed in cells and xenografts with and without drug treatment. Specificity was further determined by comparing tumor localization of a fluorescently labeled analogue with DAKO HercepTest. Results: [18F]GE-226 uptake was 11- to 67-fold higher in 10 HER2-positive versus HER2-negative cell lines in vitro independent of lineage. Uptake in HER2-positive xenografts was rapid with net irreversible binding kinetics making possible the distinction of HER2-negative [MCF7 and MCF7-p95HER2: NUV60 (%ID/mL) 6.1 ± 0.7; Ki (mL/cm3/min) 0.0069 ± 0.0014] from HER2-positive tumors (NUV60 and Ki: MCF7-HER2, 10.9 ± 1.5 and 0.015 ± 0.0035; MDA-MB-361, 18.2 ± 3.4 and 0.025 ± 0.0052; SKOV-3, 18.7 ± 2.4 and 0.036 ± 0.0065) within 1 hour. Tumor uptake correlated with HER2 expression determined by ELISA (r2 = 0.78), and a fluorophore-labeled tracer analogue colocalized with HER2 expression. Tracer uptake was not influenced by short-term or continuous treatment with trastuzumab in keeping with differential epitope binding, but reflected HER2 degradation by short-term NVP-AUY922 treatment in SKOV-3 xenografts (NUV60: 13.5 ± 2.1 %ID/mL vs. 9.0 ± 0.9 %ID/mL for vehicle or drug, respectively). Conclusions: [18F]GE-226 binds with high specificity to HER2 independent of cell lineage. The tracer has potential utility for HER2 detection, irrespective of prior trastuzumab treatment, and to discern HSP90 inhibitor-mediated HER2 degradation. Clin Cancer Res; 20(6); 1632–43. ©2014 AACR.
Epidermolysis bullosa pruriginosa: dystrophic epidermolysis bullosa with distinctive clinicopathological features
Authors: J.A. McGRATH, O.M.V. SCHOFIELD, R.A.J. EADY
Journal: British Journal of Dermatology (1994)

We report a study of eight unrelated adult patients with a highly distinctive phenotype of dystrophic epidermolysis bullosa. It is characterized clinically by pruritus, lichenified or nodular prurigo‐like lesions, violaceous linear scarring, occasional trauma‐induced blistering, excoriations, milia, Nail dystrophy and, in some cases, albopapuloid lesions on the trunk, The scarring is most evident on the limbs, particularly on the shins, with relative sparing elsewhere. Intact blisters are rarely seen. Physical signs were present at birth in three patients, but in the others skin manifestations were first noticed between 6 months and 10 years of age. Five cases are sporadic, but three of the eight patients have a history of familial involvement, with autosomal dominant inheritance in two cases and recessive transmission in the other case. Studies of the dermal‐epidermal junction showed alterations in the number and ultrastructure of anchoring fibrils in lesional, perilesional and non‐lesional skin, consistent with a diagnosis of dominant or localized recessive dystrophic epidermolysis bullosa. These patients represent an unusual, poorly recognized form or expression of dystrophic epidermolysis bullosa which has features in common with a variety of acquired inflammatory dermatoses.
Evidence for the Royal Commission — Ethical Responsibilities for Doctors — Alcohol Abuse
Authors: John Lister
Journal: New England Journal of Medicine (1977)

As the Royal Commission inquiring into the National Health Service (NHS) proceeds with its work, many bodies have been publishing the evidence that they have submitted to the commissioners. The evidence that the British Medical Association (BMA) plans to submit, subject to the approval of a special representative meeting, has now been published.1 It is a long document in which it is argued that the NHS is underfinanced, overorganized and beset by manpower problems and falling morale. After pointing out that, contrary to some erroneous impressions, the BMA has always been in favor of the concept and creation of the . . .
Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study
Authors: Ola Landgren, Robert A. Kyle, Ruth M. Pfeiffer, Jerry A. Katzmann, Neil E. Caporaso, Richard B. Hayes, Angela Dispenzieri, Shaji Kumar, Raynell J. Clark, Dalsu Baris, Robert Hoover, S. Vincent Rajkumar
Journal: Blood (2009)
An Unusual Perforation of The Esophagus
Authors: Howard Hyde
Journal: JAMA (1971)

To the Editor.—  Your readers may find some interest in this account of an unusual case.  Report of a Case.—  On Dec 23, 1969, a 67-year-old woman became nauseated while travelling by car early in the afternoon, and vomited. She did not consider herself seriously ill and completed the trip. Late in the afternoon nausea recurred, with pain in the left side of the chest radiating to the left shoulder.  Upon the patient's arrival in the hospital emergency room, her skin was cool and moist, and blood pressure was 100/70 mm Hg. An electrocardiogram showed deviation of the S-T segments and the initial impression was that she had suffered a myocardial infarction. The patient's condition was considered precarious.  On the following morning, the patient's condition seemed improved. The blood pressure had risen. X-ray films of the chest revealed almost complete collapse of the left lung with much air and fluid
Results of eVALuate study of hysterectomy techniques: Conversion to open surgery should not be regarded as major complication
Authors: Simon W Atkinson
Journal: BMJ (2004)

EDITOR—Although Garry et al look closely at outcomes for different surgical techniques in hysterectomy, I am concerned about the criteria they use to classify major complications.1

It is routine practice, at least in laparoscopic cholecystectomy, to seek patients' …
Disinfection of Cystoscopes by Subatmospheric Steam and Steam and Formaldehyde at 80 C
Authors: V. G. Alder, J. C. Gingell, J. P. Mitchell
Journal: BMJ (1971)

A new method of disinfection adapted for endoscopic instruments uses low temperature steam at 80°C or steam and formaldehyde at 80°C. The process has considerable advantages over existing methods and more closely approaches the ideal requirements.
There's No Free Lunch
Authors: William R. Hendee
Journal: JAMA (1991)

Nuclear energy and ionizing radiation are technologies that frequently are viewed with special concern by the public. Alarm often is expressed when these technologies are used for purposes such as generation of electrical power, exploration of material properties, and development of military weapons. Exposure to ionizing radiation is particularly troublesome because the risks are due to forces outside the range of the human senses. Radiation frequently is portrayed by the entertainment and news media as a technology that causes horrific effects as a result of exposure. We have all experienced this portrayal in movies, on television, and in popular literature.<sup>1</sup>As a consequence, few (if any) of us are totally objective in evaluating radiation, irrespective of our scientific and medical understanding. Certainly the average person does not view this technology objectively. Of course, exposure to ionizing radiation does entail risks. We have known about the adverse consequences of exposure
146 PROGNOSIS OF 375 URSODEOXYCHOLIC ACID-TREATED PATIENTS WITH PRIMARY BILIARY CIRRHOSIS. A FOLLOW-UP TO 17 YRS
Authors: E.M. Kuiper, B.E. Hansen, R.A. de Vries, J.W. den Ouden-Muller, K.J. van Erpecum, H.R. van Buuren
Journal: Journal of Hepatology (2008)
Mitral valve prolapse. Two-dimensional echocardiographic and angiographic correlation.
Authors: B W Gilbert, R A Schatz, O T VonRamm, V S Behar, J A Kisslo
Journal: Circulation (1976)

In order to define baseline descriptive criteria for the diagnosis of mitral valve prolapse with cross-sectional echocardiography, 49 patients undergoing catheterization were examined by a real-time, two-dimensional phased array echocardiographic imaging system. Angiography was used to separate patients into two distinct groups: 15 with normal mitral valve function and 34 with definite mitral valve prolapse. Systolic mitral leaflet and annulus motion were then observed in each patient and similarities and differences were noted between the two groups of patients. Correlative M-mode echocardiographic data were available in 37 patients. Certain two-dimensional echocardiographic findings restricted to the angiographically proven mitral valve prolapse group were defined: 1) posteriorly displaced coaptation of the leaflets, 2) systolic superior movement of one or both mitral leaflets above the level of the mitral ring, and 3) a systolic curling motion of the posterior mitral ring on its adjacent myocardium. One or more of these abnormalities were found in all 34 patients with angiographic mitral valve prolapse. When mitral valve prolapse does occur, the results of two-dimensional echocardiography would suggest that both leaflets are usually involved.
Identification of Novel Isoforms of the<i>EML4-ALK</i>Transforming Gene in Non–Small Cell Lung Cancer
Authors: Young Lim Choi, Kengo Takeuchi, Manabu Soda, Kentaro Inamura, Yuki Togashi, Satoko Hatano, Munehiro Enomoto, Toru Hamada, Hidenori Haruta, Hideki Watanabe, Kentaro Kurashina, Hisashi Hatanaka, Toshihide Ueno, Shuji Takada, Yoshihiro Yamashita, Yukihiko Sugiyama, Yuichi Ishikawa, Hiroyuki Mano
Journal: Cancer Research (2008)

Abstract The genome of a subset of non–small-cell lung cancers (NSCLC) harbors a small inversion within chromosome 2 that gives rise to a transforming fusion gene, EML4-ALK, which encodes an activated protein tyrosine kinase. Although breakpoints within EML4 have been identified in introns 13 and 20, giving rise to variants 1 and 2, respectively, of EML4-ALK, it has remained unclear whether other isoforms of the fusion gene are present in NSCLC cells. We have now screened NSCLC specimens for other in-frame fusion cDNAs that contain both EML4 and ALK sequences. Two slightly different fusion cDNAs in which exon 6 of EML4 was joined to exon 20 of ALK were each identified in two individuals of the cohort. Whereas one cDNA contained only exons 1 to 6 of EML4 (variant 3a), the other also contained an additional 33-bp sequence derived from intron 6 of EML4 (variant 3b). The protein encoded by the latter cDNA thus contained an insertion of 11 amino acids between the EML4 and ALK sequences of that encoded by the former. Both variants 3a and 3b of EML4-ALK exhibited marked transforming activity in vitro as well as oncogenic activity in vivo. A lung cancer cell line expressing endogenous variant 3 of EML4-ALK underwent cell death on exposure to a specific inhibitor of ALK catalytic activity. These data increase the frequency of EML4-ALK–positive NSCLC tumors and bolster the clinical relevance of this oncogenic kinase. [Cancer Res 2008;68(13):4971–6]
Neuroethology of releasing mechanisms: Prey-catching in toads
Authors: Jörg-Peter Ewert
Journal: Behavioral and Brain Sciences (1987)

Abstract “Sign stimuli” elicit specific patterns of behavior when an organism's motivation is appropriate. In the toad, visually released prey-catching involves orienting toward the prey, approaching, fixating, and snapping. For these action patterns to be selected and released, the prey must be recognized and localized in space. Toads discriminate prey from nonprey by certain spatiotemporal stimulus features. The stimulus-response relations are mediated by innate releasing mechanisms (RMs) with recognition properties partly modifiable by experience. Striato-pretecto-tectal connectivity determines the RM's recognition and localization properties, whereas medialpallio-thalamo-tectal circuitry makes the system sensitive to changes in internal state and to prior history of exposure to stimuli. RMs encode the diverse stimulus conditions referring to the same prey object through different combinations of “specialized” tectal neurons, involving cells selectively tuned to prey features. The prey-selective neurons express the outcome of information processing in functional units consisting of interconnected cells. Excitatory and inhibitory interactions among feature-sensitive tectal and pretectal neurons specify the perceptual operations involved in distinguishing the prey from its background, selecting its features, and discriminating it from predators. Other connections indicate stimulus location. The results of these analyses are transmitted by specialized neurons projecting from the tectum to bulbar/spinal motor systems, providing a sensorimotor interface. Specific combinations of such projective neurons – mediating feature- and space-related messages – form “command releasing systems” that activate corresponding motor pattern generators for appropriate prey-catching action patterns.
Consumer group calls for antidiabetes drug to be withdrawn
Authors: J. Lenzer
Journal: BMJ (2012)

A consumer group has petitioned the US Food and Drug Administration to pull the antidiabetes drug liraglutide from the market because of safety concerns. It warns that other drugs in its class may have similar effects to varying degrees.

Public Citizen’s Health Research Group, a non-profit consumer advocacy organisation based in Washington, DC, said that liraglutide (marketed as Victoza by Novo Nordisk)—a glucagon-like peptide-1 (GLP-1) analogue drug used as a once daily injection for type 2 diabetes—is associated with higher than expected rates of pancreatitis, thyroid cancer, and kidney failure.

The drug was approved by the FDA in January 2010 over the objections of an agency safety reviewer, Karen Mahoney. In its petition Public Citizen cites Mahoney’s recommendation against …
Women need warnings about harmful effects of obesity in pregnancy, says European project
Authors: Z. Kmietowicz
Journal: BMJ (2015)

Strategies are needed to reduce the prevalence of obesity in women of childbearing age because of the longlasting effects on the mothers and their children, a major European project has concluded.

The chances of developing cardiovascular disease, cerebrovascular disease, and type 2 diabetes are all greater in people born to mothers who were overweight during their late pregnancy, showed the results of more than 13 000 people who were followed from their birth in the 1930s and ’40s to the age of 60-70.

The findings were from the Developmental ORIgins of healthy and unhealthy AgeiNg: the role of maternal obesity (DORIAN) consortium,1 funded by the European Commission’s Framework Programme that began in January 2012. The project aimed to better understand the …
Mutation status and clinical outcome of 89 imatinib mesylate-resistant chronic myelogenous leukemia patients: a retrospective analysis from the French intergroup of CML (Fi(ϕ)-LMC GROUP)
Authors: F E Nicolini, S Corm, Q-H Lê, N Sorel, S Hayette, D Bories, T Leguay, L Roy, S Giraudier, M Tulliez, T Facon, F-X Mahon, J-M Cayuela, P Rousselot, M Michallet, C Preudhomme, F Guilhot, C Roche-Lestienne
Journal: Leukemia (2006)
Obstetrics for Students
Authors: Irwin H. Kaiser
Journal: JAMA (1965)

In his preface Professor Townsend states that it has long been the practice of lecturers in obstetrics at the University of Melbourne to supply the undergraduates with printed notes. Apparently the present book is an expansion and revision of such notes by Professor Townsend and his colleagues.  This technique does not assure successful production of a textbook. For one thing, much of the text is in outline form and consists of dogmatic remarks bare of explanation. The absence of medical references fails to assist the student in gaining access to such explication on his own. On the other hand, the special didactic qualities of the author do not emerge from the austere schematic presentations.  Much of the book is specifically oriented to Australian conditions in the use of hospitals and public and private practice. A patient is referred to as being barrier-nursed, a term unfamiliar to me. Only two obstetrical
Randomized Phase II Trial of Sorafenib with Temsirolimus or Tipifarnib in Untreated Metastatic Melanoma (S0438)
Authors: Kim A. Margolin, James Moon, Lawrence E. Flaherty, Christopher D. Lao, Wallace L. Akerley, Megan Othus, Jeffrey A. Sosman, John M. Kirkwood, Vernon K. Sondak
Journal: Clinical Cancer Research (2012)

Signaling pathway stimulation by activating mutations of oncogenes occurs in most melanomas and can provide excellent targets for therapy, but the short-term therapeutic success is limited by intrinsic and acquired resistance. The mitogen-activated protein kinase and phosphoinositide 3-kinase/AKT/mTOR pathways are activated in most cutaneous melanomas. The purpose of this trial was to prospectively evaluate 2 molecularly targeted drug combinations in patients with untreated metastatic melanoma.