tbuckley/cabot-search huggingface dataset:
A 360-degree overview of paediatric NAFLD: Recent insights
Authors: Valerio Nobili, Gianluca Svegliati-Baroni, Anna Alisi, Luca Miele, Luca Valenti, Pietro Vajro
Journal: Journal of Hepatology (2012)

Non-alcoholic fatty liver disease (NAFLD) is a multi-faceted disorder, which ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) with/without fibrosis. The effects of specific risk factors, such as obesity and sedentary lifestyle, on predisposing genetic settings eventually lead to the development of NAFLD in children. The complex interplay between genes and environment in NAFLD pathogenesis is sustained by multiple mechanisms that involve liver crosstalk with other organs and tissues, especially gut and adipose tissue. Unfortunately, natural history of paediatric NAFLD is lacking, and the etiopathogenesis is still in the process of being defined. Potential early predictors and suitable non-invasive diagnostic tools can be discovered based on the pathogenetic mechanisms and histological patterns. This will also help design novel treatments and a comprehensive and successful management strategy for patients. In this review, we discuss the recent advances made in genetics, etiopathogenesis, diagnosis, and therapeutic management of NAFLD, focusing especially on the obesity-related steatotic liver condition.
Clinical Trial of Ilidar, a New Dibenzazepine Adrenergic Blocking Drug, in the Treatment of Peripheral Vascular Diseases and Miscellaneous Complaints
Authors: HAROLD D. GREEN, HUGH H. DUBOSE
Journal: Circulation (1954)

Ilidar, a new adrenergic blocking drug, has been administered to 116 patients; follow-up was adequate on 86. The drug was highly effective in patients with predominantly vasospastic disorders and in patients with postphlebetic syndrome, and moderately effective in patients with thromboangiitis and arteriosclerosis. Most patients could tolerate 50 to 75 mg. three to four times a day. Side effects were principally those to be expected from the moderate postural hypotension associated with effective sympathetic blockade, namely, weakness, dizziness, nausea.
Revving the Throttle on an Oncogene: CDK8 Takes the Driver Seat
Authors: Ron Firestein, William C. Hahn
Journal: Cancer Research (2009)

The Wnt/beta-catenin pathway plays an important role in initiation in most, if not all, colon cancers. Prior work has provided important insights into the regulation of beta-catenin stability in the cytoplasm; however, relatively little is known about the mechanism by which beta-catenin activates gene transcription in the nucleus. Using genetic approaches, studies in human colon cancers and Drosophila have identified CDK8 as a colon cancer oncogene that regulates beta-catenin transcriptional activity. These convergent observations provide new insights into the regulation of nuclear beta-catenin activity and identify a novel therapeutic target for beta-catenin-driven malignancies.
Identification of a Gene Expression Signature Associated with Recurrent Disease in Squamous Cell Carcinoma of the Head and Neck
Authors: Matthew A. Ginos, Grier P. Page, Bryan S. Michalowicz, Ketan J. Patel, Sonja E. Volker, Stefan E. Pambuccian, Frank G. Ondrey, George L. Adams, Patrick M. Gaffney
Journal: Cancer Research (2004)

Abstract Molecular studies of squamous cell carcinoma of the head and neck (HNSCC) have demonstrated multiple genetic abnormalities such as activation of various oncogenes (Ras, Myc, epidermal growth factor receptor, and cyclin D1), tumor suppressor gene inactivation (TP53 and p16), and loss of heterozygosity at numerous chromosomal locations. Despite these observations, accurate and reliable biomarkers that predict patients at highest risk for local recurrence have yet to be defined. In an effort to identify gene expression signatures that may serve as biomarkers, we studied 41 squamous cell carcinoma tumors (25 primary and 16 locally recurrent) from various anatomical sites and 13 normal oral mucosal biopsy samples from healthy volunteers with microarray analysis using Affymetrix U133A GeneChip arrays. Differentially expressed genes were identified by calculating generalized t tests (P &amp;lt; 0.001) and applying a series of filtering criteria to yield a highly discriminant list of 2890 genes. Hierarchical clustering and image generation using standard software were used to visualize gene expression signatures. Several gene expression signatures were readily identifiable in the HNSCC tumors, including signatures associated with proliferation, extracellular matrix production, cytokine/chemokine expression, and immune response. Of particular interest was the association of a gene expression signature enriched for genes involved in tumor invasion and metastasis with patients experiencing locally recurrent disease. Notably, these tumors also demonstrated a marked absence of an immune response signature suggesting that modulation of tumor-specific immune responses may play a role in local treatment failure. These data provide evidence for a new gene expression-based biomarker of local treatment failure in HNSCC.
FIXATION OF FRACTURES OF THE CLAVICLE: ANOTHER METHOD
Authors: J. E. M. Thomson
Journal: JAMA (1926)

My object here is to describe a technic of applying fixation to fractures of the clavicle, using old and well tried principles, with especial reference to fractures of the outer third of the clavicle. Most textbooks on fractures deal lightly with the possibilities and prognosis of fractures of the clavicle. Alinement and apposition, according to various writers, mean little to the ultimate outcome of the case. The primary object of all fixation is to hold the shoulder of the affected side well back and up. The T splint, cross or barrel stay application of fixation offers an excellent medium for holding these fragments. However, in my experience most of these fractures have been in men, and it has been extremely difficult to keep the splints in proper position. They demand constant attention and adjusting. In several instances, satisfactory position of the fragments has been lost to a certain extent by
B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ
Authors: Elisabeth Salzer, Elisangela Santos-Valente, Stefanie Klaver, Sol A. Ban, Wolfgang Emminger, Nina Kathrin Prengemann, Wojciech Garncarz, Leonhard Müllauer, Renate Kain, Heidrun Boztug, Andreas Heitger, Klaus Arbeiter, Franz Eitelberger, Markus G. Seidel, Wolfgang Holter, Arnold Pollak, Winfried F. Pickl, Elisabeth Förster-Waldl, Kaan Boztug
Journal: Blood (2013)
Institutional Conflict of Interest
Authors: E J Emanuel, D Steiner
Journal: New England Journal of Medicine (1995)

Financial conflicts of interest in a research setting can adversely affect patient care, teaching, and research. Discussions of these conflicts ordinarily focus on issues that arise when individual physicians and biomedical scientists conduct research in which they have a financial interest.118 Less attention has been paid to the conflicts of interest that arise when health care institutions have a financial stake in the research conducted in their laboratories and clinics.19,20 This relative inattention persists despite the increased pressure on health care institutions to seek new sources of revenue to fund their activities and the government's encouragement of the . . .
Topical application of α‐tocopherol modulates the antioxidant network and diminishes ultraviolet‐induced oxidative damage in murine skin
Authors: None Lopez‐Torres, None Thiele, None Shindo, None Han, None Packer
Journal: British Journal of Dermatology (1998)

The aim of this study was to investigate the effects of topical α‐tocopherol application on epidermal and dermal antioxidants and its ability to prevent ultraviolet (UV)‐induced oxidative damage. Hairless mice received topical applications of α‐tocopherol 24 h before a single, acute UV irradiation (10 × minimal erythemal dose). The four major antioxidant enzymes (catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase), hydrophilic and lipophilic antioxidants, and lipid hydroperoxides, markers of oxidative damage, were assayed in both epidermis and dermis of hairless mice. Topical α‐tocopherol treatment increased dermal superoxide dismutase activity by 30% (P< 0.01) and protected epidermal glutathione peroxidase and superoxide dismutase from depletion after UV irradiation. Total and reduced glutathione levels in the epidermis increased by 50% after the topical treatment (P< 0.05), as did dermal ascorbate levels (by 40%; P< 0.01). The topical treatment increased α‐tocopherol levels both in the epidermis (62‐fold) and the dermis (22‐fold; P< 0.001 in each layer). Furthermore, α‐tocopherol treatment significantly reduced the formation of epidermal lipid hydroperoxides after UV irradiation (P< 0.05). These results demonstrate that topical administration of α‐tocopherol protects cutaneous tissues against oxidative damage induced by UV irradiation in vivo, and suggest that the underlying mechanism of this effect involves the up‐regulation of a network of enzymatic and non‐enzymatic antioxidants.
A Case Report on California's Proposition 65
Authors: Eric Stephen Berger
Journal: JAMA (1989)

To the Editor. —  I hope that the article entitled Sound Science in the Implementation of Public Policy1 was placed inJAMAto ascertain whether your readers were actually paying attention. Well, this reader was.  The explanation of Proposition 65 given in this article was a bit esoteric. Essentially, this  prevention legislation requires labeling of all consumer products if even the slightest measurable amounts of man-made carcinogens or teratogens are present; these are minuscule levels that, for most of the listed substances, pose no real risk to anyone. Naturally occurring toxic substances are exempt, as are chemical pollutants produced by all government-run facilities!  There are obvious, glaring deficiencies in the Proposition 65 legislation, as follows:  First, Proposition 65 defines a significant amount as a detectable amount. In fact, sophisticated technological methods allow detection of quantity designations such as parts per quadrillion. No epidemiologic data exist to support the claim
SOME POINTS IN CONNEXION WITH CATARACT EXTRACTION
Authors: R. H. Elliot
Journal: BMJ (1929)

THE d(lviee Oivn to cataract l)ativilt ini--E111rope( vlies so greatly with different surgeons, ald(l i so) ofteni opposed to mly owN-tpractice, which hias beeni fomnded on nimany thou,salds of operations for cataralct, thlat in compliance wvitlh requests from various soues thlat I should restate ly views, I desire to do so shortly.IThe Stage at Which the Opecration Should bc Unidcrtakcen.Die usual advice giveni is that a patienit must wait unitil the cataract is mature before uln(lergoinig operation, evTen if tlie .sight in the oplposite eye is so defective as to make htim or helr nearly helpless, or at least partlyN.dependelnt on others.The first point I wvouldl( insist oni i.s that the exact date for operationi should blc decided after a careful consi(leration of a1 the factors in each inldividual case.One cannot lay down a gereral hard-v.-and-fastrule for the guidance of students.The patient's a.ge, the state of hiis lhealth, hiis prospects of life, the conidition of tlhe second eye, and a number of other factors must be careftilly weighel before gi-ing any definiite adv-ice.A few points may bo considered wn-ith piofit.A patient is frequently told that if the second-eve sces II-ell) it is a mistake to have thl first one touchced.Stich adv-ice sceems to iuie em'iinently nisound in a number of cases.
Mitochondria in heart failure
Authors: M. G. Rosca, C. L. Hoppel
Journal: Cardiovascular Research (2010)

This review focuses on the evidence accumulated in humans and animal models to the effect that mitochondria are key players in the progression of heart failure (HF). Mitochondria are the primary source of energy in the form of adenosine triphosphate that fuels the contractile apparatus, and are thus essential for the pumping activity of the heart. We evaluate changes in mitochondrial morphology and alterations in the main components of mitochondrial energetics, such as substrate utilization and oxidative phosphorylation coupled with the level of respirasomes, in the context of their contribution to the chronic energy deficit and mechanical dysfunction in HF.
TCT-848 Clinical Impact Of Paravalvular Leaks On Biomarkers And Survival After Transcatheter Aortic Valve Implantation
Authors: Dimitry Schewel, Christian Frerker, Jury Schewel, Felix Meinke, Thomas Thielsen, Klaus Blaschke, Felix Kreidel, Karl-Heinz Kuck, Ulrich Schäfer
Journal: Journal of the American College of Cardiology (2012)
Malaria Control Insecticide Residues in Breast Milk: The Need to Consider Infant Health Risks
Authors: Hindrik Bouwman, Henrik Kylin
Journal: Environmental Health Perspectives (2009)

In many parts of the world, deliberate indoor residual spraying (IRS) of dwellings with insecticides to control malaria transmission remains the only viable option, thereby unintentionally but inevitably also causing exposure to inhabitants. Because mothers are exposed to insecticides via various routes, accumulated residues are transferred to infants via breast milk, in some cases exceeding recommended intake levels. Except for dichlorodiphenyltrichloroethane (DDT), safety of residues of other insecticides in breast milk has not been considered during World Health Organization Pesticide Evaluation Scheme (WHOPES) evaluations. However, very little is known of the health risks posed by these chemicals to infants who, in developing countries, breast-feed for up to 2 years.We evaluated the need for WHOPES to include breast milk as a potentially significant route of exposure and risk to infants when evaluating the risks during evaluation of IRS insecticides.We present evidence showing that neurologic and endocrine effects are associated with pyrethroids and DDT at levels equal or below known levels in breast milk.Because millions of people in malaria control areas experience conditions of multiple sources and routes of exposure to any number of insecticides, even though lives are saved through malaria prevention, identification of potential infant health risks associated with insecticide residues in breast milk must be incorporated in WHOPES evaluations and in the development of appropriate risk assessment tools.
<i>p53</i>-Altered <i>FBXW7</i> Expression Determines Poor Prognosis in Gastric Cancer Cases
Authors: Takehiko Yokobori, Koshi Mimori, Masaaki Iwatsuki, Hideshi Ishii, Ichiro Onoyama, Takeo Fukagawa, Hiroyuki Kuwano, Keiichi I. Nakayama, Masaki Mori
Journal: Cancer Research (2009)

A molecular target associated with the progression of gastric cancer has not yet been uncovered. FBXW7 is a tumor suppressor gene transcriptionally controlled by p53 that plays a role in the regulation of cell cycle exit and reentry via c-Myc degradation. Few studies have addressed the clinical significance of FBXW7 expression in gastric cancer. Therefore, we examined FBXW7 mRNA expression to determine its clinicopathologic significance in 100 cases of gastric cancer. Low expression levels of FBXW7 in primary gastric cancer contributed to malignant potential, such as lymph node metastasis (P = 0.0012), tumor size (P = 0.0003), and poor prognosis (P = 0.018). In comparison with 52 cases of gastric cancer without the p53 mutation, 29 cases with the mutation exhibited lower expression levels of FBXW7 (P = 0.0034), revealing a significant relationship between p53 mutation and FBXW7 expression. Furthermore, we found that gastric cancer patients who had low FBXW7 expression levels and p53 mutation had a distinctively poor prognosis in comparison with other subgroups (P = 0.0033). In conclusion, we showed a role for p53 in the transcriptional regulation of FBXW7 expression in clinical gastric cancer cases and showed that disruption of both p53 and FBXW7 contributes to poor prognosis.
Congenital anterior abdominal wall defects in England and Wales 1987-93: retrospective analysis of OPCS data
Authors: K. H Tan, M. D Kilby, M. J Whittle, B. R Beattie, I. W Booth, B. J Botting
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objectives</b>: Analysis of incidence and characteristics of congenital abdominal wall defects, with special reference to the differences between the incidence of gastroschisis and exomphalos (omphalocele). <b>Design</b>: Retrospective analysis using data from the Office of Population Censuses and Surveys (recoded to differentiate exomphalos and gastroschisis) and the National Congenital Malformation Notification Scheme. <b>Setting</b>: England and Wales, 1987 to 1993. <b>Results</b>: 1043 congenital anterior abdominal wall defects were notified within the seven year study period. Of these, 539 were classified as gastroschisis, 448 as exomphalos, 19 as "prune belly syndrome," and 37 as "unclassified." Gastroschisis doubled in incidence from 0.65 in 1987 to 1.35 per 10 000 total births in 1991, with little further change; the incidence of exomphalos decreased from 1.13 to 0.77 per 10 000 births. The overall incidence of notified congenital abdominal wall defects was 2.15 per 10 000 total births. Gastroschisis was associated with a lower overall maternal age than exomphalos and with a significantly lower proportion of additional reported congenital malformations (5.0%) than in the cohort with exomphalos (27.4%) (odds ratio 0.14, 95% confidence interval 0.09 to 0.22; P&lt;0.001). The sex ratio of the two cohorts was the same. The incidence of gastroschisis and exomphalos was higher in the northern regions of England than in the south east of the country. <b>Conclusions</b>: The national congenital malformation notification system showed an increasing trend in the incidence of fetuses born with gastroschisis and a progressive decreasing incidence of exomphalos in England and Wales between 1987 and 1993. Although the reasons for this are likely to be multifactorial, a true differential change seems likely. The observed increase in incidence of gastroschisis relative to exomphalos and the differentiation in maternal age have implications for resource management within the NHS and warrant further epidemiological monitoring. Regional differences may be due to a dietary or environmental factor, which requires further study. <h3>Key messages</h3> Gastroschisis was also associated with a significantly lower proportion of additional reported congenital malformations Younger mothers are significantly more likely than older mothers to have a child with gastroschisis The incidence of congenital abdominal wall defects seemed to be higher in the regions in the north than in the south east of England
Adolescent Feeble-minded in Law and Practice
Authors: J. F. MacMahon
Journal: BMJ (1952)

STAPH. PYOGENES BRITJISIdrugs must be rare, and no such strains were found.This was supported by previous unpublished work by one of us (R. A. S.) in which an examination of '501 strains of Staph.pyogenes collected prior to 1950 failed also to show any strains resistant to aureomycin.Reports in the American literature suggest that resistant strains are becom- ing common among hospital patients in the United States.We have isolated strains resistant to aureomycin and strains resistant to chloramphenicol from patients in hospital.It is presumably only a matter of time before these organisms appear amongst the general population.In view of the recent suggestion (Banks, 1952) that chlor- amphenicol is the drug of choice for treating penicillinresistant staphylococcal infections, it is of some interest that the usual minimum inhibitory concentration of this drug for the organism in our series of strains was 32 times greater than that of aureomycin and 16 times that of terramycin. SummaryTwo hundred strains of Staph.pyogenes isolated from out-patients with staphylococcal infections of the skin and subcutaneous tissues have been tested for their sensitivity to penicillin, streptomycin, aureomycin, chloramphenicol, and terramycin.Of the strains tested 16% were resistant to penicillin.No strains markedly resistant to the other antibiotics were found.We would like to thank Professor L.
Diagnosis of cystic fibrosis.
Authors: A G Davidson, C M Anderson
Journal: BMJ (1971)

the risk of mutual interference between folic acid and anticonvulsants in the intestine.89If our interpretation of our findings is correct, then we have found a simple, harm- less, and very cheap method for the treat- ment and prevention of folic acid deficiency in chronic epileptics, which would also re- move the necessity for very large numbers of tedious time-consuming laboratory estimations of serum and red cell folate concentra- tions in such patients.This treatment might also have a place in the treatment of chronic psychiatric patients and geriatric patients admitted in a poor dietary state.-Weare, etc.,
A 56-Year-Old Woman With Chronic Fatigue Syndrome
Authors: Anthony L. Komaroff
Journal: JAMA (1997)

<h3>Dr Delbanco:</h3> Ms H is a 56-year-old educator currently on medical leave of absence. She has an 11-year history of chronic fatigue that at times has been disabling. She has commercial managed care health insurance through her work. Prior to her illness, Ms H was well, a successful and energetic teacher who was physically very active. In 1986 she developed the sudden onset of profound fatigue, about 1 month after a flulike illness characterized by fever, chills, myalgias, and sore throat. She thought she had infectious mononucleosis, but laboratory tests did not confirm the diagnosis. Titers for Epstein-Barr infection were found to be elevated soon thereafter. Since that time, she has noted extraordinary weakness, finding herself able to walk only a few blocks, followed by exhaustion that forces her to spend many hours in bed. She often finds herself unable to concentrate. She reports she periodically has had "swollen glands"
Significance of High Degree Atrioventricular Block in Acute Posterior Myocardial Infarction
Authors: MICHAEL ROTMAN, GALEN S. WAGNER, ROBERT A. WAUGH
Journal: Circulation (1973)

This report evaluates the morbidity and mortality, during hospitalization and follow-up, of a subgroup of patients with posterior or diaphragmatic myocardial infarction (PDMI) who developed high degree A-V block via a type I mechanism and in the absence of power failure (pulmonary edema or cardiogenic shock). This subgroup was not at any higher risk of hospital morbidity, hospital mortality, or 1-year mortality than three other groups: (a) patients with PDMI but neither high degree A-V block nor initial power failure; (b) patients with other infarct sites who developed high degree A-V block in the absence of power failure; and (c) patients with other infarct sites but neither high degree A-V block nor initial power failure. The significance of subgrouping patients with high degree A-V block by the quantity of clinical heart failure is exemplified by a review of the literature and the present study.
Depression and Coronary Heart Disease
Authors: Judith H. Lichtman, J. Thomas Bigger, James A. Blumenthal, Nancy Frasure-Smith, Peter G. Kaufmann, François Lespérance, Daniel B. Mark, David S. Sheps, C. Barr Taylor, Erika Sivarajan Froelicher
Journal: Circulation (2008)

Depression is commonly present in patients with coronary heart disease (CHD) and is independently associated with increased cardiovascular morbidity and mortality. Screening tests for depressive symptoms should be applied to identify patients who may require further assessment and treatment. This multispecialty consensus document reviews the evidence linking depression with CHD and provides recommendations for healthcare providers for the assessment, referral, and treatment of depression.