tbuckley/cabot-search huggingface dataset:
Female genital mutilation
Authors: S. Bewley, S. Creighton, C. Momoh
Journal: BMJ (2010)

Paediatricians should resist its medicalisation

Female genital mutilation is defined by the World Health Organization as any procedure that involves partial or total removal of the external genitalia or other injury to the female genital organs for non-medical reasons.1 Worldwide, 100-140 million girls and women are estimated to live with the consequences of such practices.

Although a graded classification of types exists,2 female genital mutilation is recognised internationally as a violation of human rights with no health benefits. Immediate risks include haemorrhage, infection, and death. Long term consequences include menstrual problems, infertility, psychosexual and psychological difficulties, and adverse obstetric outcomes including caesarean section, perineal trauma, haemorrhage, and perinatal death.3 So why did the American Academy of Paediatrics (AAP) amend an earlier policy to suggest that United States law could be changed to allow doctors to “nick” female genitalia, as a cultural compromise?4 Women’s rights organisations, the World Health Organisation, and the UK Royal Colleges of Obstetrics and Gynaecology and Paediatrics and Child Health all expressed dismay.5 6 The AAP released a statement on 27 May to say that they have withdrawn the policy,7 but …
Determinants and outcomes of congestive heart failure complicating acute coronary syndromes: observations from the global registry of acute coronary events
Authors: Philippe Gabríel Steg, Omar Dabbous, Alain Cohen-Solal, Marie-Claude Aumont, Christopher P. Cannon, José López-Sendón, Andrzej Budaj, Werner Klein
Journal: Journal of the American College of Cardiology (2002)
Expression of Platelet-Activating Factor Receptor in Human Carotid Atherosclerotic Plaques
Authors: Isabelle Brochériou, Dominique Stengel, Lillemor Mattsson-Hultén, Jana Stankova, Marek Rola-Pleszczynski, Fabien Koskas, Olov Wiklund, Yves Le Charpentier, Ewa Ninio
Journal: Circulation (2000)

Background —Human monocyte-derived macrophages synthesize numerous proinflammatory and prothrombotic substances, including lipid mediators, such as platelet-activating factor (PAF), which may play a major role in the onset and perpetuation of atherosclerotic lesions. In addition, both monocytes and macrophages express PAF receptors (PAF-R). The expression of PAF-R is transcriptionally downregulated by oxidized LDL in in vitro primary cultures of monocyte/macrophages. In this study, we evaluated the expression of PAF-R in human carotid plaque tissue, in foam cells isolated from human carotid plaques, and in primary cultures of umbilical smooth muscle cells (SMCs). Methods and Results —We show that PAF-R was expressed at low levels in foam cells compared with monocyte/macrophages in plaques, as assessed by immunohistochemical staining and in situ hybridization. In addition, low levels of mRNA were also detected by RT-PCR in isolated human carotid foam cells. A prominent finding of our study was the demonstration that contractile SMCs were positive for PAF-R, and its mRNA was extracted from primary cultures of umbilical SMCs. Conclusions —As macrophages loose their inflammatory phenotype on transformation into foam cells, they may equally loose their capacity of defense against aggression. We postulate that the diminished expression of PAF-R may be deleterious in the context of plaque formation and progression. The observation that arterial SMCs of contractile phenotype express PAF-R opens new avenues concerning the migration of these cells from media to intima and atherosclerotic plaque formation.
Hepatitis C-associated B-cell non-Hodgkin lymphomas. Epidemiology, molecular signature and clinical management
Authors: Jan Peveling-Oberhag, Luca Arcaini, Martin-Leo Hansmann, Stefan Zeuzem
Journal: Journal of Hepatology (2013)

There is ample epidemiologic evidence for an association of chronic hepatitis C virus (HCV) infection with B-cell non-Hodgkin lymphoma (B-NHL). B-NHL subtypes most frequently associated with HCV are marginal zone lymphoma and diffuse large B-cell lymphoma. The most convincing evidence for a causal relationship between HCV infection and lymphoma development is the observation of B-NHL regression after HCV eradication by antiviral therapy (AVT). In fact, for indolent HCV-associated B-NHL, first-line AVT instead of standard immune-chemotherapy might be considered. Molecular mechanisms of HCV-NHL development are still poorly understood. Three general theories have emerged to understand the HCV-induced lymphomagenesis: (1) continuous external stimulation of lymphocyte receptors by viral antigens and consecutive proliferation; (2) HCV replication in B cells with oncogenic effect mediated by intracellular viral proteins; (3) permanent B-cell damage, e.g., mutation of tumor suppressor genes, caused by a transiently intracellular virus ("hit and run" theory). This review systematically summarizes the data on epidemiology, interventional studies, and molecular mechanisms of HCV-associated B-NHL.
THE SURGICAL CONSIDERATION OF CONGENITAL AND DEVELOPMENTAL DEFECTS LEADING TO OBSTINATE CONSTIPATION
Authors: JOHN G. CLARK
Journal: JAMA (1910)

To arrive properly at a basis for the study of constipation and tympanitis, with their coincident autointoxication, one must start well back of the condition of disability and investigate the various embryologic, anatomic, and physiologic factors which may ultimately promote the train of pathologic symptoms. Probably no condition is more lightly viewed by physicians in general than constipation, possibly because it is so common, and possibly, also, because in many instances it is more or less easily set aside by laxatives. Unless, therefore, this symptom becomes so exaggerated as to suggest a possible obstruction, it is usually viewed with professional equanimity. There is a growing tendency to look on the various laboratories of the human body as the generating ground, not only of physiologic, but under abnormal conditions of various pathologic products, in one instance beneficent, in the other very deleterious to health. The thyroid has already taken its place
Resting energy expenditure in lung and colon cancer
Authors: Daniel W. Nixon, Michael Kutner, Steven Heymsfield, Ann T. Foltz, Chandra Carty, Susan Seitz, Katie Casper, William K. Evans, Khursheed N. Jeejeebhoy, John M. Daly, David Heber, Heinz Poppendiek, Freddie A. Hoffman
Journal: Metabolism (1988)
Zuckerman Report and Radiology
Authors: R. Thursfield, J. H. E. Bergin, E. H. Burrows
Journal: BMJ (1974)

E.B. virus, like other viruses, sometimes does produce lymphomas in animals.I would not be frightened by the prospect of developing infectious mononucleosis after E.B. virus in- oculation and I would discount the danger of developing a Burkitt tumour in the short span of life left to me.The question I would regard as of the utmost importance to me is whether, by E.B. virus inoculation, my tumour could be made once more drugsensitive.The answer to this question is un- known but could, like many another scienti- fic problem, be elucidated by being put to the test.-I am, etc.,
Abstract 5185: RNAi screen identifies a synthetic lethal interaction between Pim1 overexpression and Plk1 inhibition.
Authors: Sarki Abdulkadir, Riet Vander Meer, Meejeon Roh
Journal: Cancer Research (2013)

Abstract PIM1 kinase is overexpressed in many tumor types including lymphomas and prostate cancer, where it is known to cooperate with the MYC oncogene in promoting tumorigenicity. PIM1 enhances MYC stability and transcriptional activity. Knowledge of the vulnerabilities of Pim1-expressing tumor cells will be of great value in efforts to develop novel anti-cancer therapeutics. Here we have used RNAi screening to identify genes whose depletion is detrimental to Pim1-overexpressing cells. We screened a collection of 570 siRNAs targeting cell cycle, apoptosis, serine-threonine kinase and tyrosine kinase genes for their effects on the viability of Pim1-expressing RWPE1 prostate epithelial cells. We identified the mitotic regulator polo-like kinase (PLK1) as a gene whose depletion is particularly detrimental to the viability of Pim1-expressing prostate cancer cells in vitro and in vivo. Inhibition of PLK1 by shRNA or by the chemical inhibitor BI2536 in prostate cancer xenograft model resulted in a dramatic inhibition of tumor progression in Pim1-overexpressing cells. Interestingly Pim1-overexpressing cells are more prone to mitotic arrest followed by apoptosis. Furthermore, inhibition of Plk1 activity led to the reduction of MYC protein levels both in vitro and in vivo. These results suggest that PLK1 inhibition may be particularly effective against PIM1-expressing tumors due, at least in part, to the fact that PLK1 inhibition reduces MYC protein levels. Citation Format: Sarki Abdulkadir, Riet Vander Meer, Meejeon Roh. RNAi screen identifies a synthetic lethal interaction between Pim1 overexpression and Plk1 inhibition. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5185. doi:10.1158/1538-7445.AM2013-5185 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Better evidence must be collected on childhood injuries
Authors: T T Ohn, M G Miller, G Sparks
Journal: BMJ (1999)

EDITOR—The data presented by Sibert et al on preventing playground injuries are crucial for future evidence based interventions in injury prevention.1 Nevertheless, the primary step of collecting evidence, especially quality causal information, for paediatric injuries is still a major challenge. Despite the gradual development of surveillance centres in England,2 information on injuries still remains inadequate. In particular, reliable morbidity data that could be translated into preventive strategies are still rare in many areas. Kirklees, west Yorkshire, is one such area, and we report the paediatric fractures there. …
Cryptogenic Hemoptysis
Authors: Laurent Savale, Antoine Parrot, Antoine Khalil, Martine Antoine, Jonathan Théodore, Marie-France Carette, Charles Mayaud, Muriel Fartoukh
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Data on hemoptysis of unknown origin (i.e., "cryptogenic") are scarce and the outcome of patients affected is controversial.To describe the clinical spectrum and course of patients with cryptogenic hemoptysis, as well as pathologic findings when surgery is performed.A cohort of 81 patients referred for cryptogenic hemoptysis after clinical evaluation, chest radiography, fiberoptic bronchoscopy, and computed tomographic scan to a respiratory intermediate care and intensive care unit, from December 1995 to August 2004, with a prospective follow-up by visit or telephone interview.The 81 patients (69 males) had a mean cumulative volume of hemoptysis averaging 190 ml on admission. First-line conservative measures and bronchial artery embolization controlled hemoptysis in 73 patients (90%). Emergency surgery was performed in six patients (7%) because of failure of bronchial artery embolization, and secondary surgery was scheduled in a seventh patient. A total of 73 patients were followed for a mean of 47 (+/- 35) months. No lung cancer developed. Hemoptysis recurred in 10 patients (4 within the first year; 6 between 1 and 8 yr later), 2 of whom underwent surgery. A specific bronchial vascular involvement (Dieulafoy disease) was demonstrated in five of the nine patients who had undergone surgery, especially in those with high amounts of bleeding.Cryptogenic hemoptysis may be a life-threatening condition. Nonsurgical approaches provide immediate control of bleeding in most patients with cryptogenic hemoptysis, with few recurrences in both short and long terms. Dieulafoy disease of the bronchus, unsuspected after routine imaging investigations, may be involved in a subset of patients yet to be determined.
652. In Vivo Evaluation of an Oncolytic Adenovirus Regulated by Hypoxia
Authors: Sergia Bortolanza, Jesus Prieto, Pilar Alzuguren, Elvira Carro, Ruben Hernandez-Alcoceba
Journal: Molecular Therapy (2006)

Conditionally replicative adenoviruses (CRAD, also called oncolytic adenoviruses) are a new platform for the treatment of cancer. Despite the promising results in pre-clinical models, their efficacy in humans is hampered by several factors, including poor biodistribution in solid tumors. Here we describe the construction and characterization of Ad-DHLuc, a new CRAD designed for in vivo evaluation of viral replication and spread under hypoxic conditions. The replication of Ad-DHLuc is directed to solid tumors by different mechanisms: (i) transcriptional control of E1A gene by a hypoxia-responsive promtorer, (ii) transcriptional control of the E4 region by an E2F-responsive promotoer, and (iii) deletion of the CR2 domain of E1A. The virus carries the luciferase gene inserted into the E3 region (substitution of the gp19k/6.7k genes), in order to link transgene expression and viral replication. We provide evidence that the virus is activated by hypoxia in cancer cells. Using bioluminiscence detection and virus quantification, we show that Ad-DHLuc can replicate in human hepatocellular carcinoma xenografts growing in nude mice. This CRAD will allow the evaluation of new strategies aimed to improve the distribution of the virus in solid tumors.
Help Wanted: Participants for Clinical Trials
Authors: M. Mitka
Journal: JAMA (2003)

events included mild to moderate dry mouth, anorexia, insomnia, and headache, which decreased as treatment continued; no clinically significant changes in pulse or blood pressure were seen. Research is also under way to examine long-term effects of atomoxetine, which the US Food and Drug Administration approved in 2002 as the first nonstimulantmedication forADHDand the first drug specifically for treating adults. Atomoxetine improves attention and reduces symptoms of hyperactivity and impulsivity, said Spencer, lead author of the first published report on this medication (Am J Psychiatry. 1998;155:693-695). A noncontrolled prescription medication, atomoxetine does not appear to have abuse potential, and does not exacerbate tics (a potential adverse effect associated with the use of psychostimulants), he said. David Michelson, MD, senior medical director at Lilly Research Laboratories, Indianapolis, Spencer, and other researchers at 31 medical centers in North America conducted two parallel randomized, double-blind placebocontrolled 10-week studies of atomoxetine (up to 120 mg/d) in 536 adults with ADHD. In the trial, funded by Lilly, the drug proved superior to placebo in reducing core ADHD symptoms, as documented by investigator-rated Conners Adult ADHD Rating Scales and clinician assessment, as well as subjects’ self-reports. While associated with modest increases in blood pressure and heart rate, atomoxetine was found to be well tolerated and safe (Biol Psychiatry. 2003;53:112-120). Subsequently, 384 of the subjects entered an open 97-week extension, receiving dosages titrated up to a maximum of 160 mg/d. An interim analysis after 34 weeks, presented at the APA meeting, showed that two thirds of subjects achieved at least a 30% decrease in symptoms.
Valid Consent for Genomic Epidemiology in Developing Countries
Authors: Dave A Chokshi, Mahamadou A Thera, Michael Parker, Mahamadou Diakite, Julie Makani, Dominic P Kwiatkowski, Ogobara K Doumbo
Journal: PLoS Medicine (2007)

The Policy Forum allows health policy makers around the world to discuss challenges and opportunities for improving health
Type III Hyperlipoproteinemia: Paradoxical Hypolipidemic Response to Estrogen
Authors: RAMPRATAP S. KUSHWAHA
Journal: Annals of Internal Medicine (1977)

Exogenous estrogens (ethinyl estradiol, 1 µg/kg body weight per day), which stimulate triglyceride production in normal women and those with endogenous hypertriglyceridemia, were found to exert a paradoxical, hypolipidemic effect in six subjects (five women, one man) with type III hyperlipoproteinemia on diets both of normal and of fat-free, high-carbohydrate composition. Moreover, very low-density (VLD) lipoprotein lipid and apolipoprotein composition and electrophoretic mobility became normal during estrogen administration in these subjects. Levels of normal VLD lipoproteins remained mildly to moderately elevated in a type IV lipoprotein pattern. Estrogen withdrawal promptly restored the type III pattern with its abnormal enrichment of VLD lipoproteins with apolipoprotein E (the arginine-rich peptide). These findings suggest that estrogens facilitate the assimilation of chylomicron and VLD lipoprotein remnants, a defect that appears likely to represent the metabolic abnormality underlying type III hyperlipoproteinemia.
Improved Coronary Artery Definition With T2-Weighted, Free-Breathing, Three-Dimensional Coronary MRA
Authors: René M. Botnar, Matthias Stuber, Peter G. Danias, Kraig V. Kissinger, Warren J. Manning
Journal: Circulation (1999)

Three-dimensional (3D) navigator-gated and prospectively corrected free-breathing coronary magnetic resonance angiography (MRA) allows for submillimeter image resolution but suffers from poor contrast between coronary blood and myocardium. Data collected over >100 ms/heart beat are also susceptible to bulk cardiac and respiratory motion. To address these problems, we examined the effect of a T2 preparation prepulse (T2prep) for myocardial suppression and a shortened acquisition window on coronary definition.Eight healthy adult subjects and 5 patients with confirmed coronary artery disease (CAD) underwent free-breathing 3D MRA with and without T2prep and with 120- and 60-ms data-acquisition windows. The T2prep resulted in a 123% (P<0. 001) increase in contrast-to-noise ratio (CNR). Coronary edge definition was improved by 33% (P<0.001). Acquisition window shortening from 120 to 60 ms resulted in better vessel definition (11%; P<0.001). Among patients with CAD, there was a good correspondence with disease.Free-breathing, T2prep, 3D coronary MRA with a shorter acquisition window resulted in improved CNR and better coronary artery definition, allowing the assessment of coronary disease. This approach offers the potential for free-breathing, noninvasive assessment of the major coronary arteries.
Mechanisms of angina relief after nifedipine: a hemodynamic and myocardial metabolic study.
Authors: H Emanuelsson, S Holmberg
Journal: Circulation (1983)

To elucidate the mechanisms of action of nifedipine in angina pectoris, 14 patients were studied before and after sublingual administration of 10 mg nifedipine. Systemic and coronary hemodynamic and myocardial metabolic measurements were taken at rest and during pacing. At the pacing rate that induced pain in the control situation, no patient experienced angina after nifedipine administration. Lactate production during control turned into extraction after nifedipine administration (p less than .05), and the double product was reduced (p less than .001). Systemic and coronary vascular resistance were reduced by 26% (p less than .001) and 19% (p less than .005), respectively. Systolic blood pressure fell from 160 +/- 29 to 127 +/- 25 mm Hg (p less than .001) and diastolic from 100 +/- 14 to 79 +/- 11 mm Hg (p less than .001). Pulmonary artery diastolic blood pressure fell from 14 +/- 4 to 10 +/- 3 mm Hg (p less than .01). When the pacing rate was further increased after nifedipine administration until pain developed, the double product and the degree of lactate production were the same as during pain before nifedipine was administered. The pacing rate was 131 +/- 12 compared with 119 +/- 13 during control (p less than .001). Both the systolic and diastolic blood pressures were still significantly reduced compared with control pacing values, 131 +/- 26 mm Hg (p less than .01) and 84 +/- 13 mm Hg (p less than .01), respectively. Our data demonstrate that the antianginal efficiency can be partly explained by afterload reduction, which decreases myocardial oxygen consumption. The data also suggest additional mechanisms, possibly an increase in collateral flow, direct dilatation of stenotic parts of epicardial arteries, or a decrease in myocardial back pressure secondary to reduced left ventricular filling pressure.
The Thyroid and the Heart
Authors: H. Cookson
Journal: BMJ (1959)

CARDIAC PAINJDBRrr pain which kills only sometimes, but which maims all the time unless under careful and wise supervision.Miss E. M. Goldberg, of the medical research unit, and Miss M. E. Druett, almoner to the cardiac department, of the London Hospital, have given me great help in the interrogation of those patients who had passed through an attack of cardiac infarction.
Drug-induced conditioning in congestive heart failure.
Authors: C V Leier, P Huss, R P Lewis, D V Unverferth
Journal: Circulation (1982)

Continuous 72-hour infusions of dobutamine reportedly effect sustained clinical improvement in patients with congestive heart failure. This study was designed to determine if shorter, more frequent infusions, delivered in an outpatient setting, elicit a similar response. Twenty-six patients with moderately severe congestive heart failure were randomized, 11 into a control group and 15 into a dobutamine treatment group. Baseline data were collected for 4 weeks in each group. Thereafter, the dobutamine treatment group received 4-hour infusions of dobutamine weekly for 24 weeks. Systolic time intervals, echocardiography, cardiac index and treadmill exercise tolerance were used to follow the progress of the control and dobutamine treatment groups. The ratio of preejection period to left ventricular ejection time and the cardiac index did not change significantly in either group. The velocity of circumferential fiber shortening and the percent change in the minor axis of the left ventricle during systole improved modestly (p less than 0.05) above baseline in the dobutamine group after 14 weeks of treatment and above the corresponding control values (p less than 0.05) after 22 weeks. Exercise tolerance (duration) improved 25--51% (all p less than 0.05) above baseline in the dobutamine group compared with 10--17% (all p greater than 0.05 vs baseline) in the control group. Heart rate at maximal exercise did not change significantly from baseline for either group and did not differ significantly between the two groups. Functional classification improved in 12 of 15 dobutamine treatment patients and in only two of 11 control patients (p less than 0.05). In our patients with congestive heart failure, weekly 4-hour dobutamine infusions did not elicit a major change in resting left ventricular function; however, exercise performance and clinical status improved considerably.
Reversal of Catabolism by Beta-Blockade after Severe Burns
Authors: David N. Herndon, David W. Hart, Steven E. Wolf, David L. Chinkes, Robert R. Wolfe
Journal: New England Journal of Medicine (2001)

The catecholamine-mediated hypermetabolic response to severe burns causes increased energy expenditure and muscle-protein catabolism. We hypothesized that blockade of β-adrenergic stimulation with propranolol would decrease resting energy expenditure and muscle catabolism in patients with severe burns.