tbuckley/cabot-search huggingface dataset:
Histological features and HLA class II alleles in hepatitis C virus chronically infected patients with persistently normal alanine aminotransferase levels
Authors: C Renou
Journal: Gut (2002)

<b>Objective:</b> A significant proportion of individuals with chronic hepatitis C virus (HCV) infection have persistently normal alanine aminotransferase (ALT) levels. Although data are controversial, such patients usually have weaker histological damage and a lower progression rate of fibrosis. The aims of this study were: (1) to compare demographic, virological, and histological parameters of HCV patients with normal ALT values with those of HCV patients with elevated ALT levels; and (2) to determine whether HLA class II alleles contribute to the persistence of normal ALT levels in HCV patients. <b>Patients and methods:</b> Eighty three patients with chronic HCV infection and persistently normal ALT values (group 1) and 233 patients with chronic HCV infection and elevated ALT levels (group 2) were studied. Histological features were expressed using Knodell and Metavir scores. HLA DRB1* and DQB1* genotyping was performed using hybridisation with sequence specific oligonucleotides after genomic amplification. The κ2 and Fisher’s exact tests were used to compare discrete variables and phenotype frequencies between the two groups, and Wilcoxon’s test was used for continuous variables. A multivariate logistic regression model was used to determine which variables predicted normal ALT values. <b>Results:</b> ALT levels were correlated with the severity of liver damage. In group 1, 93% of patients had an F0 or F1 Metavir index of fibrosis compared with 47% of patients in group 2 (p&lt;0.001). A longer duration of infection (p&lt;0.001) and increased DRB1*11 phenotype frequency (pc=0.03) were observed among patients with normal ALT. The two groups did not differ with regard to the mode of contamination or viral genotype. After logistic regression, young age (p=0.0008), female sex (p=0.01), long duration of infection (p=0.0001), and HLA DRB1*11 (p=0.050) were more strongly associated with persistence of normal ALT. <b>Conclusions:</b> Our study confirms that patients with chronic hepatitis C and normal ALT levels have less severe liver disease than those with elevated ALT levels. This particular biochemical outcome may be explained, at least in part, by host immunogenetic factors such as the presence of HLA-DRB1*11.
Role of Oxidant Stress on AT1 Receptor Expression in Neurons of Rabbits With Heart Failure and in Cultured Neurons
Authors: Dongmei Liu, Lie Gao, Shyamal K. Roy, Kurtis G. Cornish, Irving H. Zucker
Journal: Circulation Research (2008)

We have previously reported that the expression of Angiotensin II (Ang II) type 1 receptors (AT1R) was increased in the rostral ventrolateral medulla (RVLM) of rabbits with chronic heart failure (CHF) and in the RVLM of normal rabbits infused with intracerebroventricular (ICV) Ang II. The present study investigated whether oxidant stress plays a role in Ang II–induced AT1R upregulation and its relationship to the transcription factor activator protein 1 (AP1) in CHF rabbits and in the CATHa neuronal cell line. In CATHa cells, Ang II significantly increased AT1R mRNA by 123±11%, P &lt;0.01; c-Jun mRNA by 90±20%, P &lt;0.01; c-fos mRNA by 148±49%, P &lt;0.01; NADPH oxidase activity by 126±43%, P &lt;0.01 versus untreated cells. Tempol and Apocynin reversed the increased expression of AT1R mRNA, c-Jun mRNA, c-fos mRNA, and superoxide production induced by Ang II. We also examined the effect of ICV Tempol on the RVLM of CHF rabbits. Compared to vehicle treated CHF rabbits, Tempol significantly decreased AT1R protein expression (1.6±0.29 versus 0.88±0.16, P &lt;0.05), phosphorylated Jnk protein (0.4±0.05 versus 0.2±0.04, P &lt;0.05), cytosolic phosphorylated c-Jun (0.56±0.1 versus 0.36±0.05, P &lt;0.05), and nuclear phosphorylated c-Jun (0.67±0.1 versus 0.3±0.08, P &lt;0.01). Tempol also significantly decreased the AP-1–DNA binding activity in the RVLM of CHF rabbits compared to the vehicle group (9.14×10 3 versus 41.95×10 3 gray level P &lt;0.01). These data suggest that Ang II induces AT1R upregulation at the transcriptional level by induction of oxidant stress and activation of AP1 in both cultured neuronal cells and in intact brain of rabbits. Antioxidant agents may be beneficial in CHF and other states where brain Ang II is elevated by decreasing AT1R expression through the Jnk and AP1 pathway.
Isoenzymes of Carbohydrate Metabolism in Primary Cultures of Hepatocytes From Thioacetamide–Induced Rat Liver Necrosis: Responses to Growth Factors
Authors: Maria Cascales, Paloma Martin-Sanz, Alberto Alvarez, Miguel Sanchez-Pérez, Carmen Diez Fernández, Lisardo Boscá
Journal: Hepatology (1992)

Hepatocytes isolated from the liver of rats after a necrotizing dose of thioacetamide (6.6 mmol/kg) were used to study the postnecrotic process of liver regeneration. Flow cytometry analysis revealed populations of dedifferentiated hepatocytes exhibiting physical properties (size and fluorescence emission at 530 nm) similar to those found in fetal (22 days old) liver cells. The percentage of these cells increased progressively from 24 to 48 and 72 hr after thioacetamide administration. In primary cultures of hepatocytes the effects of phorbol 12-myristate 13-acetate, bombesin and insulin were investigated on the 6-phosphofructo 2-kinase/fructose 2,6 bisphosphate system. Bombesin and insulin stimulated 6-phosphofructo 2-kinase activity and fructose 2,6-bisphosphate content both in control and in thioacetamide-treated hepatocytes. However, phorbol 12-myristate 13-acetate stimulated 6-phosphofructo 2-kinase activity and increased fructose 2,6-bisphosphate concentration in thioacetamide-treated liver cells, whereas no similar response was found in hepatocytes from control rats. The response of postnecrotic thioacetamide-treated hepatocytes to phorbol 12-myristate 13-acetate was similar to that obtained from 22-day-old fetal liver cells, which reveals that different methods might control fructose 2,6-bisphosphate content and therefore the mechanisms of glycolysis and gluconeogenesis at this regulatory step. The lack of response to glucagon of glycogen phosphorylase a and 6-phosphofructo 2-kinase from thioacetamide-treated hepatocytes may indicate that the expression of specific enzymes of carbohydrate metabolism undergoes transitions to less-differentiated isoenzymatic forms. Moreover, the isoenzyme pattern of hexokinases elicits a complete disturbance in glucokinase and hexokinases activities.(ABSTRACT TRUNCATED AT 250 WORDS)
New public health and old rhetoric
Authors: P J Vandenbroucke
Journal: BMJ (1994)

There is a discipline in medicine that over the past 200 years has been known by various names: sanitary medicine, public hygiene, public health, social medicine, and community medicine. Its newest incarnation proudly calls itself “the new public health.”1

Academically the discipline was buried repeatedly because it produced “mere rhetoric.”2,3 The first time this happened was before the turn of the 19th century. The successful hygienic and sanitarian movement of the middle of that century divorced itself from bacteriology, the upcoming science of the 1880s, because bacteriology could not really explain why epidemics happened at certain places and certain times and to certain people. The members of the movement had a point, in retrospect, but their adamant opposition to the new science led to their academic downfall and even ridicule. Hygienism was seen as only “soft” rhetoric, while “hard” bacteriological science would give the real explanations. Nobody had proved hygienists wrong, it was just that nobody was interested in their kind of argument any more.4 Chairs and institutes of hygiene were turned into …
Cohesiveness and Hostility in Group Psychotherapy
Authors: HERMANN A. ROETHER, JOSEPH J. PETERS
Journal: American Journal of Psychiatry (1972)

The authors discuss two theoretical constructs, group cohesiveness and exposure to hostility, in relation to group psychotherapy. Three hypotheses that link cohesiveness and hostility to treatment outcome were tested with data derived from a group psychotherapy program for sex offenders on probation. Analyses showed that exposure to hostility is positively related to outcome, whereas cohesiveness is unrelated but has a negative tendency toward successful outcome.
ANTIGEN-ANTIBODY REACTIONS BETWEEN LAYERS ADSORBED ON BUILT UP STEARATE FILMS
Authors: Eliot F. Porter, Alwin M. Pappenheimer
Journal: The Journal of Experimental Medicine (1939)

By adsorbing antigens and antibodies on barium stearate multilayers immunological reactions at surfaces have been studied. Pneumococcus polysaccharide specific antibody systems using purified antibodies from both horse and rabbit sera were investigated. The polysaccharides failed to show visible adsorption, but by alternate treatment with antibody and polysaccharide several layers of antibody could be specifically deposited. With the diphtheria toxin-antitoxin system antitoxin was found to adsorb to layers of toxin but not conversely. The reaction, however, was not specific. Molecular weights calculated from the thickness of adsorbed protein layers, using dissymmetry factors, roughly correspond to molecular weights calculated from sedimentation and diffusion constants.
Randomized Phase III Trial Comparing Irinotecan/Cisplatin With Etoposide/Cisplatin in Patients With Previously Untreated Extensive-Stage Disease Small-Cell Lung Cancer
Authors: Nasser Hanna, Paul A. Bunn, Corey Langer, Lawrence Einhorn, Troy Guthrie, Thaddeus Beck, Rafat Ansari, Peter Ellis, Michael Byrne, Mark Morrison, Subramanian Hariharan, Benjamin Wang, Alan Sandler
Journal: Journal of Clinical Oncology (2006)

Purpose Etoposide and cisplatin (EP) has been a standard treatment for extensive-disease small-cell lung cancer (SCLC). An earlier phase III trial reported improved survival for patients receiving irinotecan plus cisplatin (IP) versus EP. Our trial was designed to determine if a modified weekly regimen of IP would provide superior survival with less toxicity than EP. Patients and Methods The primary objective was to compare overall survival in extensive-disease SCLC patients randomly assigned to receive IP (n = 221) or EP (n = 110). Patients were randomly assigned in 2:1 ratio to cisplatin 30 mg/m 2 intravenously (IV) + irinotecan 65 mg/m 2 IV on days 1 and 8 every 21 days, or cisplatin 60 mg/m 2 IV on day 1, and etoposide 120 mg/m 2 IV on days 1 to 3 every 21 days for at least four cycles, until progressive disease, or until intolerable toxicity resulted. Results Selected grade 3/4 toxicities for IP/EP were: neutropenia (36.2% v 86.5%; P &lt; .01), febrile neutropenia (3.7% v 10.4%; P = .06), anemia (4.8% v 11.5%; P = .02), thrombocytopenia (4.3% v 19.2%; P &lt; .01), vomiting (12.5% v 3.8%; P = .04), and diarrhea (21.3% v 0%; P &lt; .01). There was no significant difference in response rates (48% v 43.6%), median time to progression (4.1 v 4.6 months), or overall survival (median survival time, 9.3 months v 10.2 months; P = .74). Conclusion Treatment with this dose and schedule of IP did not result in improved survival when compared with EP. Fewer patients receiving IP had grade 3/4 anemia, thrombocytopenia, neutropenia, and febrile neutropenia compared with patients receiving EP, but more had grade 3/4 diarrhea and vomiting.
A survey on gastroenterology training in Europe
Authors: R Bisschops
Journal: Gut (2002)

Background: Specialist training in gastroenterology and hepatology is not standardised in different European countries. Aim: The aim of this survey was to assess the different teaching and socioeconomic aspects of training programmes in Europe. Methods: Seventy questionnaires were distributed to last year trainees or newly graduated gastroenterologists. Forty two respondents (60%) from 34 major training centres in 10 different European countries replied. Results: Overall, the data revealed major diversity for all aspects analysed, between and within the different European countries. Both the duration of training (range 4–10.4 years) and workload (range 48.5–89.2 hours per week) differed markedly between countries. The average number of endoscopic procedures (gastroscopies, range 300–2600; colonoscopies, range 73–550; endoscopic retrograde cholangiopancreatographies, range 1–385) differed also. One third of last year trainees reported that they felt uncertain in some endoscopic procedure. The European trainee was on call for 5–6 nights a month on average (range 1–8). Monthly wages differed considerably between countries, ranging from 767 to 2180 Euro. Conclusion: We found major differences in the professional aspects and socioeconomic conditions of gastroenterologist/hepatologist training in 10 different European countries, probably leading to differences in quality of training. In several countries or centres the average number of procedures was below the threshold issued by the European Board of Gastroenterlogy or the American Gastroenterological Association. Issuing a European diploma for gastroenterology is a valuable effort towards meeting this problem. Further studies are needed to re-evaluate the training programmes in Europe and to define threshold numbers and technical end points for assessment of endoscopic skills.
Reversible Inhibitors of LSD1 as Therapeutic Agents in Acute Myeloid Leukemia: Clinical Significance and Progress to Date
Authors: Daniel P. Mould, Alison E. McGonagle, Daniel H. Wiseman, Emma L. Williams, Allan M. Jordan
Journal: Medicinal Research Reviews (2014)

Abstract In the 10 years since the discovery of lysine‐specific demethylase 1 (LSD1), this epigenetic eraser has emerged as an important target of interest in oncology. More specifically, research has demonstrated that it plays an essential role in the self‐renewal of leukemic stem cells in acute myeloid leukemia (AML). This review will cover clinical aspects of AML, the role of epigenetics in the disease, and discuss the research that led to the first irreversible inhibitors of LSD1 entering clinical trials for the treatment of AML in 2014. We also review recent achievements and progress in the development of potent and selective reversible inhibitors of LSD1. These compounds differ in their mode of action from tranylcypromine derivatives and could facilitate novel biochemical studies to probe the pathways mediated by LSD1. In this review, we will critically evaluate the strengths and weaknesses of published series of reversible LSD1 inhibitors. Overall, while the development of reversible inhibitors to date has been less fruitful than that of irreversible inhibitors, there is still the possibility for their use to facilitate further research into the roles and functions of LSD1 and to expand the therapeutic applications of LSD1 inhibitors in the clinic.
Increased Expression of Erythropoiesis Inhibiting Cytokines (IFN-γ, TNF-α, IL-10, and IL-13) by T Cells in Patients Exhibiting a Poor Response to Erythropoietin Therapy
Authors: Angela C. Cooper, Ashraf Mikhail, Mark W. Lethbridge, D. Michael Kemeny, Iain C. Macdougall
Journal: Journal of the American Society of Nephrology (2003)

<h3>Abstract</h3> In many situations of everyday life, it is important to quickly understand a spoken message despite distraction by an already ongoing activity. Previous dual-task studies recording the N400 component of the event-related potential (ERP) have shown that auditory language comprehension can be strongly delayed by temporally overlapping additional tasks. In the current study, we investigated whether this interference is aggravated by the need for saccadic eye movements and visuospatial attention shifts in the overlapping task. In two dual-task experiments, a synonymy judgment task for spoken words was combined with a visual discrimination task at different stimulus onset asynchronies. In half of the trials, the primary visual task required a 10° exogenous saccade towards a peripheral stimulus. The timing of semantic processing in the secondary task was assessed by recording the N400. We replicated that with increasing temporal overlap between the tasks, the N400 component was strongly delayed. However, additional saccade-related processes in the primary task had no detrimental effects on concurrent spoken language processing on their own. Unexpectedly, we also observed that a preceding saccade consistently facilitated subsequent motoric processing in the visual task (as indexed by manual reaction times and the lateralized readiness potential), suggesting that saccade execution as such can significantly enhance subsequent processing.
Sclerotherapy with alcohol–a two-edged sword!
Authors: S. K. Sarin
Journal: Hepatology (1990)

Absolute alcohol is a potentially optimal agent for sclerotherapy of esophageal varices. It is cheap and readily available. We compared the efficacy and safety of alcohol with those of a commonly used sclerosing agent, polidocanol. The study was planned to include patients with previous bleeding from esophageal varices randomly assigned to one of the two treatments. After the inclusion of the first 11 patients (6 in the polidocanol group and 5 in the alcohol group), however, the trial was interrupted because of serious complications in patients treated with alcohol (four major bleeding episodes and one esophageal stenosis). The two agents were of comparable efficacy in the small sample of patients studied. The complications were related to the presence of iatrogenic esophageal ulcers which were more frequent (100% vs 30%) and significantly larger (mean, 1.4 cm vs 0.7 cm, p &lt; 0.05) in patients treated with alcohol.
Most Published Research Findings Are False—But a Little Replication Goes a Long Way
Authors: Ramal Moonesinghe, Muin J Khoury, A. Cecile J. W Janssens
Journal: PLoS Medicine (2007)

While the authors agree with John Ioannidis that "most research findings are false," here they show that replication of research findings enhances the positive predictive value of research findings being true.
Androgenetic alopecia in heterozygous carriers of a mutation in the human hairless gene
Authors: Eli Sprecher, Adel Shalata, Kamal Dabhah, Boris Futerman e, Shai Lin, Raymonde Szargel, Reuven Bergman, Rachel Friedman-Birnbaum, Nadine Cohen
Journal: Journal of the American Academy of Dermatology (2000)
Responding to AIDS, Tuberculosis, Malaria, and Emerging Infectious Diseases in Burma: Dilemmas of Policy and Practice
Authors: Chris Beyrer, Voravit Suwanvanichkij, Luke C Mullany, Adam K Richards, Nicole Franck, Aaron Samuels, Thomas J Lee
Journal: PLoS Medicine (2006)

In 2004 the Global Fund to Fight AIDS, Tuberculosis, and Malaria (“Global Fund”) awarded program grants to Burma (Myanmar) totaling US$98.4 million over five years—recognizing the severity of Burma’s HIV/AIDS and tuberculosis (TB) epidemics, and noting that malaria was the leading cause of morbidity and mortality, and the leading killer of children under five years old [1]. For those individuals working in health in Burma, these grants were welcome, indeed [2].
Changing Practice of Anticoagulation: Will Target-Specific Anticoagulants Replace Warfarin?
Authors: Gowthami M. Arepally, Thomas L. Ortel
Journal: Annual Review of Medicine (2015)

The target-specific oral anticoagulants are a class of agents that inhibit factor Xa or thrombin. They are effective and safe compared to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation and for the treatment of venous thromboembolism, and they are comparable to low-molecular-weight heparin for thromboprophylaxis after hip or knee arthroplasty. For other indications, however, such as the prevention of stroke in patients with mechanical heart valves, initial studies have been unfavorable for the newer agents, leaving warfarin the anticoagulant of choice. Further studies are needed before the target-specific anticoagulants can be recommended for patients with cancer-associated thrombosis or heparin-induced thrombocytopenia. Concerns also persist about difficulties with the laboratory assessment of anticoagulant effect and the lack of a specific reversal agent. For these reasons, we anticipate that the vitamin K antagonists will continue to be important anticoagulants for years to come.
Devastating diarrhoea caused by azathioprine: management difficulty in inflammatory bowel disease.
Authors: J Cox, T K Daneshmend, C J Hawkey, R F Logan, R P Walt
Journal: Gut (1988)

Azathioprine toxicity complicated the management of four patients with inflammatory bowel disease. All patients received the drug as adjunctive therapy to steroids when responses to the latter were poor. After a variable sensitising period the patients developed severe diarrhoea and abdominal pain and this was believed at first to be a manifestation of their underlying diseases but rechallenge with azathioprine reproduced the problem. During three episodes described emergency admission to hospital and resuscitation with intravenous fluids was required. The cases illustrate the difficulty clinicians have in recognising drug induced effects which mimic the underlying disease. When a patient suspects a reaction to azathioprine we believe any rechallenge should only be undertaken in the controlled hospital environment.
Anti-tumor necrosis factor modulates anti-CD3-triggered T cell cytokine gene expression in vivo.
Authors: C Ferran, F Dautry, S Mérite, K Sheehan, R Schreiber, G Grau, J F Bach, L Chatenoud
Journal: Journal of Clinical Investigation (1994)

De novo expression of TNF, IFN gamma, IL-3, IL-4, and IL-6 genes was initiated rapidly by treatment of mice with anti-CD3. A specific feature of this reaction was that TNF was derived exclusively from T cells. TNF was produced both as a mature soluble trimeric protein and as a 26-kD anti-TNF-reactive protein compatible with membrane-anchored TNF. Pretreatment with anti-TNF did not affect anti-CD3-triggered TNF mRNA expression in T cells. In contrast, in vivo and in vitro anti-TNF treatment upregulated anti-CD3-induced IFN gamma mRNA expression and inhibited IL-4 mRNA expression. These latter effects were not dependent on TNF neutralization: pretreatment with soluble recombinant 55-kD TNF receptor (TBPI) as an alternative TNF-neutralizing agent did not modify the anti-CD3-induced cytokine profile. These results suggest that a direct interaction between anti-TNF and T cell membrane-anchored TNF could account for the observed modulation of cytokine gene expression. The increased expression of INF gamma mRNA observed in anti-TNF-treated animals correlated with a decrease in IL-3 and IL-6 mRNA expression. Conversely, IFN gamma blockade by a neutralizing anti-IFN gamma mAb led to a substantial increase in both IL-3 and IL-6 gene expression induced by anti-CD3. Taken together, these results strongly argue for the existence, in the anti-CD3-induced cytokine cascade, of IFN gamma-dependent regulation of IL-3 production, which in turn modulates IL-6 production.