tbuckley/cabot-search huggingface dataset:
Attitudes of uk gastroenterology trainees to research and out of programme experience: results from the 2009 national academic training survey
Authors: B. Disney, E. Fogden, P. Sime, H. Ellison, M. J. Brookes
Journal: Gut (2011)

<h3>Introduction</h3> A national survey of UK gastroenterology trainees in 20071 identified high rates of participation in research and Out Of Programme Experience (OOPE). 49.6% of respondents were currently or had already undertaken OOPE. Trainees9 success at fellowship applications to the major funding bodies ranged from 23.5 to 29.9%. The changes in academic training pathways post Walport and the Modernising Medical Careers process will have implications for both academic and clinical trainees wishing to undertake a period of out-of-programme experience (OOPE), although the effects are currently unclear. Aims The aims were to determine: Trainees9 experience of OOPE Trainees9 success at research fellowship application The perceived barriers to undertaking a period of OOPE <h3>Methods</h3> A Web-based national survey of trainees in Gastroenterology in the UK was carried out in September 2009, supported by the British Society of Gastroenterology. <h3>Results</h3> 237 trainees completed the survey in 2009, 73% (n=173) male, 27% (n=64) female. All training years and regions were evenly represented. 89.9% (n=213) were in clinical training programmes, with 10.1% (n=24) in a Walport training programme. 88.7% of trainees expressed a wish to undertake OOPE/research. 55.7% (n=132) of respondents were currently in or had previously undertaken OOPE. 50% (n=61) of these had registered for a PhD and 34% (n=45) an MD. 47.7% (n=113) of trainees had completed their OOPE at the time of survey and of this group 15.9% (n=18) had received their degree. Trainees had success rates between 12.5% and 40.8% for clinical research fellowships. 94.9% (n=225) of trainees feel that attainment of a higher degree will make them more competitive at NHS consultant interviews. The most common reasons for not undertaking OOPE were related to competition for funding and personal financial implications. <h3>Conclusion</h3> The majority of trainees express a desire to undertake OOPE and rates of participation in research/OOPE remains high. UK gastroenterology trainees are competitive for major fellowship programmes. Further surveys will be needed to study the effects of MMC and Walport, as well as the effects of increasing student debt on participation in OOPE.
Early and late changes in fasting and absorptive plasma amino acids and ammonia after distal splenorenal shunt in cirrhosis
Authors: Franco Trevisani, Mauro Bernardi, Vincenzo Arienti, Pietro Scrivano, Alighieri Mazziotti, Antonino Cavallari, Daniela Patrono, Sandro Piazzi, Giuseppe Gozzetti, Giovanni Gasbarrini
Journal: Hepatology (1994)

Levels of plasma amino acids, ammonia, glucagon and insulin and their 5-hr responses to a protein feeding were evaluated before and sequentially (3 mo and 1 yr) after distal splenorenal shunt in 10 patients with cirrhosis belonging to Child-Pugh's class A or B. An index of glucagon effectiveness (plasma glucose/glucagon) was also calculated. These parameters were related to liver test results, portal vein diameter and mental state, and they were compared with those found in seven patients undergoing sclerotherapy of esophageal varices with comparable liver function (control group). Liver test results and levels of plasma insulin did not change in either group. Shunt significantly increased levels of fasting tyrosine, methionine, ornithine, arginine, histidine, ammonia and glucagon with respect to the control group; it also significantly decreased levels of leucine, valine, glucagon effectiveness and portal vein diameter. The elevation of levels of tyrosine, ammonia and the sum of arginine and ornithine was correlated directly with the increase in glucagon and inversely with the decline in glucagon effectiveness. Tyrosine increase was also correlated with the reduction of portal vein diameter. One shunted patient showed mild hepatic encephalopathy. Protein feeding did not worsen the mental state of patients before and after the operation. Surgery significantly increased the 5-hr response to the meal of gluconeogenic amino acids; its rise was again correlated with the changes in glucagon plasma levels and effectiveness. Although the absorptive levels of plasma ammonia were significantly higher 1 yr after surgery, its 5-hr response barely rose. In cirrhotic patients with a relatively preserved liver function, distal splenorenal shunt progressively worsened the fasting plasma profile of nitrogen compounds and the response to protein ingestion of gluconeogenic amino acids. The decline of portal blood flow and glucagon effectiveness may be causal factors. Despite this, the "cerebral" tolerance to a moderate oral load of protein was not reduced by surgery.
Effects of Theophylline on Diaphragmatic Strength and Fatigue in Patients with Chronic Obstructive Pulmonary Disease
Authors: Danièle Murciano, Michel Aubier, Yann Lecocguic, René Pariente
Journal: New England Journal of Medicine (1984)

We studied the effects of theophylline on diaphragmatic strength and fatigue in 15 patients with severe chronic obstructive pulmonary disease. Diaphragmatic strength was assessed by measurement of the transdiaphragmatic pressure generated at functional residual capacity during a maximal inspiratory effort against closed airways. Diaphragmatic fatigue was induced by resistive loaded breathing. The electrical activity of the diaphragm was recorded with an esophageal electrode during the fatigue runs, and the high–low ratio of the electrical signal was analyzed to assess diaphragmatic fatigue. Studies were performed before and after 7 and 30 days of theophylline administration (mean plasma level, 13±2 mg per liter). A control group received a placebo instead of theophylline. Theophylline increased maximal transdiaphragmatic pressure by 16 per cent after 7 days of administration (P<0.01), and this increase persisted after 30 days. No significant change in maximal transdiaphragmatic pressure was observed in the group given the placebo. Theophylline also suppressed diaphragmatic fatigue in all patients who received it. We conclude that theophylline has a potent and long-lasting effect on diaphragmatic strength and fatigue in patients with fixed airway obstruction. (N Engl J Med 1984; 311:349–53.)
Modulation of transforming growth factor-beta 1 antiproliferative effects on endothelial cells by cysteine, cystine, and N-acetylcysteine.
Authors: S K Das, A C White, B L Fanburg
Journal: Journal of Clinical Investigation (1992)

Early passaged bovine pulmonary artery endothelial cells exposed to 0.1-2.0 ng/ml transforming growth factor-beta 1 (TGF-beta 1) showed concentration-dependent growth inhibition, as assessed by [3H]thymidine labeling and cell counts, over a 96-h interval. Most of the inhibition of [3H]thymidine labeling measured at 96 h persisted when the medium was replaced with TGF-beta 1-free medium after 24 h, but the inhibition of labeling was prevented by the presence of anti-TGF-beta 1 antibody in the replacement medium. Additions of 2 mM cysteine, 1 mM cystine, or 2 mM N-acetylcysteine at the time of the initial addition of TGF-beta 1 blocked the inhibitory effect of TGF-beta 1 on [3H]-thymidine labeling when this was assessed after 72-96 h, but not at earlier times. Prevention of the inhibitory effect on cellular proliferation produced by cysteine, cystine and N-acetylcysteine was associated with elevation of cellular glutathione that was present at 48-96 h. There was no evidence for direct inactivation of TGF-beta 1 by the thiol-amino acids. Conditioned medium from TGF-beta 1-treated endothelial cells inhibited proliferation of mink lung carcinoma (CCL64) cells, supporting a previously reported concept of autocrine production of TGF-beta 1 by the endothelial cells. The inhibitory action of the conditioned medium was partially prevented when 1 mM cysteine was added during conditioning. Thus, TGF-beta 1 treatment of endothelial cells appears to set off autocrine production by these cells of TGF-beta 1 that perpetuates the inhibition of cellular proliferation. Replenishment of cellular glutathione with thiol-amino acids counteracts the growth-inhibitory effect of TGF-beta 1 through a currently undefined mechanism.
Let's Not Let the Genie Escape from the Bottle — Again
Authors: James E. Muller, Peter H. Stone, John E. Markis, Eugene Braunwald
Journal: New England Journal of Medicine (1981)

A BOLD and exciting new technique to protect ischemic myocardium has recently been developed. In several pilot studies carried out in patients with acute myocardial infarction, it has been shown that acutely occluded coronary arteries can be recanalized by the intracoronary injection of streptokinase or a fibrinolytic agent.1 2 3 4 5 6 If optimum care is to be provided to the million or so patients who have acute myocardial infarction each year, this technique deserves more carefully designed evaluation than that given a similarly bold and exciting technique developed a little more than a decade ago: coronary-artery bypass grafting (CABG).CABG was quickly recognized . . .
Radiotherapy audit shows less regional variation than feared
Authors: I. Torjesen
Journal: BMJ (2011)

Regional variation across England in access of patients with cancer to radiotherapy services is not as great as previously feared, shows a new detailed analysis of the provision of radiotherapy.

The analysis of radiotherapy services delivered between April 2009 and March 2010, published on 2 August, is the first that the Department of Health has undertaken in detail. From now on the data will be published annually.

In 2009-10 there were around 31 000 attendances for radiotherapy for every million people in the population and an average of 6660 attendances for each linear accelerator in regular use. The breast was the most common primary tumour site for radiotherapy (28% …
P425Cytoprotection by the NO-donor SNAP and BNP against ischemia/reperfusion injury in rat engineered heart tissue
Authors: A Gorbe, A Eder, ZV Varga, J Paloczi, A Hansen, P Ferdinandy, T Eschenhagen
Journal: Cardiovascular Research (2014)

Purpose: In vitro drug screening and disease modeling is a rapidly growing research field and may help to replace animal experiments. The aim of this study was to test the response of engineered heart tissue (EHT) to ischemia/reperfusion (I/R) and the effect of known cardioprotective molecules.
Primary Biliary Cirrhosis: A Model Autoimmune Disease
Authors: STEPHEN P. JAMES
Journal: Annals of Internal Medicine (1983)

Primary biliary cirrhosis is characterized by chronic inflammation and necrosis of the intrahepatic bile ducts and by chronic cholestasis. The presence of autoantibodies in serum, the association of this disease with other autoimmune diseases, the histologic appearance of typical hepatic lesions, the presence of bile duct lesions that resemble those seen in chronic graftversus-host disease, and the possible recurrence of a chronic cholestatic syndrome in patients having hepatic transplants indicate that immune mechanisms play a role in the syndrome's pathogenesis. Patients have diminished function of suppressor T cells that may be due to abnormal activation of suppressor T cells caused by interactions with autologous non-T cells. This nonspecific immunologic defect and other immune defects may cause the autoimmune manifestations of primary biliary cirrhosis. Treatments to arrest the disease's progress have included corticosteroids, azathioprine, cyclosporin, and D-penicillamine. These treatments, which affect immune functions, have not had a beneficial effect on the disease process. Better understanding of the pathogenesis of primary biliary cirrhosis is needed to develop specific immunotherapies.
Dosage Errors With Heparin
Authors: Wasyl Fedorciw
Journal: JAMA (1975)

To the Editor.—  Besides problems caused by misreading labels on heparin vials (231:701, 1974), most surgeons in our community still use milligrams in prescribing the dose of heparin to patients. This is probably because the US Pharmacopoeia years ago required not less than 120 USP heparin units/mg for heparin sodium derived from lungs, and not less than 140 USP units/mg for heparin sodium derived from other tissues. So, the conversion factor was accepted roughly as being 100 units/mg. As the purity of heparin sodium continues to improve, the potency may vary from 120 to 180 heparin units/mg or even more.  To obtain uniform activity from product to product, heparin sodium injection USP must be prescribed in terms of USP units only.
A Randomized Trial of Chemoradiotherapy and Chemotherapy after Resection of Pancreatic Cancer
Authors: John P. Neoptolemos, Deborah D. Stocken, Helmut Friess, Claudio Bassi, Janet A. Dunn, Helen Hickey, Hans Beger, Laureano Fernandez-Cruz, Christos Dervenis, François Lacaine, Massimo Falconi, Paolo Pederzoli, Akos Pap, David Spooner, David J. Kerr, Markus W. Büchler
Journal: New England Journal of Medicine (2004)

The effect of adjuvant treatment on survival in pancreatic cancer is unclear. We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and update the interim results.In a multicenter trial using a two-by-two factorial design, we randomly assigned 73 patients with resected pancreatic ductal adenocarcinoma to treatment with chemoradiotherapy alone (20 Gy over a two-week period plus fluorouracil), 75 patients to chemotherapy alone (fluorouracil), 72 patients to both chemoradiotherapy and chemotherapy, and 69 patients to observation.The analysis was based on 237 deaths among the 289 patients (82 percent) and a median follow-up of 47 months (interquartile range, 33 to 62). The estimated five-year survival rate was 10 percent among patients assigned to receive chemoradiotherapy and 20 percent among patients who did not receive chemoradiotherapy (P=0.05). The five-year survival rate was 21 percent among patients who received chemotherapy and 8 percent among patients who did not receive chemotherapy (P=0.009). The benefit of chemotherapy persisted after adjustment for major prognostic factors.Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on survival.
Research on Brain-Dead Patients
Authors: Robert Baker
Journal: Annals of Internal Medicine (1989)

Letters and Corrections1 January 1989Research on Brain-Dead PatientsRobert Baker, PhDRobert Baker, PhDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-110-1-88_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: Should the requirements for research on brain-dead patients be more stringent than those for brain-alive but incompetent patients? La Puma (1) raises this question in his editorial on an experiment Coller and colleagues (2) did using the circulatory and hematologic systems of a 78-year-old brain-dead patient. The experiment not only conformed to current U.S. guidelines (3) for research on human subjects, it satisfied a set of more stringent conditions Coller proposed for experimentation on "neomorts"—including an exclusion for donors of organs.La Puma argues that even these strictures are "not enough" and urges the need for more...References1. La Puma J. Discovery and disquiet: research on the brain-dead. Ann intern Med. 1988;109:606-8. LinkGoogle Scholar2. CollerScudderBergerIuliucci BLHJ. Inhibition of human platelet function in vivo with a monoclonal antibody: with observations on the newly dead as experimental subjects. Ann Intern Med. 1988;109:635-8. LinkGoogle Scholar3. Protection of human subjects, basic health and human services policy for the protection of human subjects, 45 CFR B46.103 (9) (1), 1982. Google Scholar4. Dickson D. Human experimentation roils French medicine. Science. 1987;239:1370. CrossrefGoogle Scholar5. California man's heart is transplanted without permission. The New York Times. 1988 April 24:part 1:14. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Union College Schenectady, NY 12308 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByEthics guidelines for research with the recently deadResearch on Dead PersonsAkira Akabayashi, MD, Masahiro Morioka, MA 1 January 1989Volume 110, Issue 1Page: 88-88KeywordsResearch reporting guidelines Issue Published: 1 January 1989 PDF DownloadLoading ...
Interphase cytogenetic studies of human hepatocellular carcinomas by fluorescentin situ hybridization
Authors: C Hamon-Benais, O Ingster, B Terris, M Couturier-Turpin, A Bernheim, G Feldmann
Journal: Hepatology (1996)

Although numerous allelic chromosome losses have been reported in hepatocellular carcinomas (HCC), chromosome analysis by cytogenetic methods has rarely been performed in these tumors, unlike other solid malignant tumors. The purpose of the current study was to analyze primary liver tumors by conventional cytogenetic methods and by a new molecular cytogenetic technique, called fluorescent in situ hybridization (FISH), a technique that has been recently proposed to count the number of chromosome copies in interphase nuclei with chromosome centromeric probes. Primary cultures of tumoral cells were prepared to obtain metaphases. Specific chromosomes probes 7, 17, and 20 were used to perform in situ hybridization on isolated intact tumoral cells. Seven cases of primary liver tumors (six cases of HCC and one case of benign focal hepatic nodular hyperplasia) were investigated. A few metaphases were obtained in five of the seven tumors, and in most cases numerical abnormalities were difficult to interpret. In contrast with in situ hybridization, all cases of HCC showed losses and/or gains of chromosomes. Loss of one to three chromosomes occurred in five tumors. A gain of two chromosomes was observed in two of these five tumors. In only one case, a gain of only three chromosomes occurred. In addition, a loss of chromosome 17 was recorded for the benign tumor. These results demonstrate that FISH with specific probes can provide information on chromosome number in the tumoral cells of primary liver tumors even in the absence of analyzable metaphases. This technique opens new possibilities for the investigation of chromosome abnormalities in HCC.
Comparison of the single dose pharmacokinetics of sulphasalazine in rheumatoid arthritis and inflammatory bowel disease.
Authors: C Astbury, A J Taggart, L Juby, L Zebouni, H A Bird
Journal: Annals of the Rheumatic Diseases (1990)

The pharmacokinetics of sulphasalazine and its principal metabolites in rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) were compared. Patients with RA had a significantly greater concentration of plasma sulphapyridine than patients with IBD (medians 14.0 micrograms/ml and 7.4 micrograms/ml respectively). Patients with RA also tended to maintain a higher plasma sulphapyridine concentration with time, as determined by the area under the curve (AUC), but a lower plasma sulphasalazine AUC than patients with IBD. It is suggested that more sulphasalazine may be presented to the lower bowel for cleavage to sulphapyridine and 5-aminosalicylic acid in patients with RA than in IBD. Patients with RA may also have impaired metabolism of sulphapyridine as a consequence of their disease. Together these factors may contribute to higher peak circulating sulphapyridine concentrations and may be responsible for the higher incidence of side effects of sulphasalazine treatment in patients with RA than in patients with IBD.
Phthalic anhydride allergy: development and characterization of optimized hapten–carrier conjugates for improved diagnosis
Authors: M. Pakarinen, M. Koivuluhta, N. Kalkkinen, H. Keskinen, H. Nordman, T. Estlander, O. Tupasela, R. Jolanki, A. I. Lauerma, P. Pfäffli, H. Alenius
Journal: Allergy (2002)

At present the diagnosis of IgE-mediated hypersensitivity to phthalic anhydride (PA) is based on conjugates that are not characterized or standardized. The aim of this study was to develop optimized and molecularly characterized PA conjugates that can be used to improve the diagnosis of PA-allergy.The PA conjugates were synthesized and the number of haptens bound on a carrier protein was estimated by matrix-assisted laser desorption/ionization time of light (MALDI-TOF) mass spectrometry. The ability of conjugates to bind IgE and IgG antibodies was measured by enzyme-linked immunosorbent assay (ELISA). Reactivity of the conjugates in vivo was evaluated by skin prick testing.The most active IgE-binding conjugates had a PA : HSA molar ratio of 80 : 1. In the optimal conjugates the average numbers of PA haptens per carrier molecule of human serum albumin (HSA) were 14-16. In ELISA, all 13 patients and none of the 20 controls had IgE antibodies to optimized PA conjugate. The sensitivity and specificity of the ELISA was comparable to commercial CAP RAST. PA conjugates elicited positive test results in skin prick testing showing that conjugates are immunologically active also in vivo.These results indicate that optimized and molecularly characterized PA-HSA conjugates can be used both in vitro and in vivo assays to improve the diagnosis of PA allergy.
TCT-324 Influence Of Heart Rate On A Fractional Flow Reserve Measurement In Different Epicardial Territories – A Theoretical And Experimental Study In The Stenosis Model Of Porcine Coronaries
Authors: Przemysław J. Kwasiborski, Piotr P. Buszman, Paweł Kowalczyk, Agata Krauze, Adam Janas, Grzegorz J. Horszczaruk, Pawel E. Buszman, Jacek Przybylski, Krzysztof P. Milewski
Journal: Journal of the American College of Cardiology (2014)
Indoleamine 2,3-dioxygenase-1 (IDO1) expression by childhood acute myeloid leukemias inhibits T-cell production of IFN-γ and confers an unfavorable prognosis
Authors: Sergio Rutella, Valentina Folgiero, Perla Filippini, Valentina Bertaina, Riccardo Masetti, Marco Zecca, Giuseppina Li Pira, Giovanni F Torelli, Anna Maria Testi, Alice Bertaina, Andrea Pession, Franco Locatelli
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Indoleamine 2,3-dioxygenase 1 (IDO1) degrades tryptophan into kynurenine (KYN) and other immune suppressive molecules that inhibit effector T cells and promote regulatory T-cell differentiation. We have previously shown that IDO1 mRNA and protein are detectable in blast cells from
House dust mite control measures for asthma: systematic review
Authors: P. C. Gøtzsche, H. K. Johansen
Journal: Allergy (2008)

The major allergen in house dust comes from mites. We performed a systematic review of the randomized trials that had assessed the effects of reducing exposure to house dust mite antigens in the homes of people with mite‐sensitive asthma, and had compared active interventions with placebo or no treatment. Fifty‐four trials (3002 patients) were included. Thirty‐six trials assessed physical methods (26 mattress covers), 10 chemical methods and eight a combination of chemical and physical methods. Despite the fact that many trials were of poor quality and would be expected to exaggerate the reported effect, we did not find an effect of the interventions. For the most frequently reported outcome, peak flow in the morning (1565 patients), the standardized mean difference was 0.00 (95% confidence interval (CI) −0.10 to 0.10). There were no statistically significant differences in number of patients improved (relative risk 1.01, 95% CI 0.80–1.27), asthma symptom scores (standardized mean difference −0.04, 95% CI −0.15 to 0.07) or in medication usage (standardized mean difference −0.06, 95% CI −0.18 to 0.07). Chemical and physical methods aimed at reducing exposure to house dust mite allergens cannot be recommended.