tbuckley/cabot-search huggingface dataset:
OC-114 EMR vs ESD for the resection of large rectosigmoid lesions: data from a large UK centre
Authors: G Longcroft-Wheaton, P Bhandari
Journal: Gut (2012)

<h3>Introduction</h3> Endoscopic resection of large benign rectal lesions is becoming established as an attractive alternative to surgery. However, the optimal technique is not clear. This series compares the experience of EMR and ESD in a tertiary referral centre. <h3>Methods</h3> A prospective review of patients undergoing endoscopic resection of neoplastic polyps in the rectosigmoid colon. Patients were tertiary referrals from experienced consultants. The polyps were considered technically challenging due to size, difficult lesion access or recurrences on previous EMR scars. Referral was made prior to surgical referral. All lesions were assessed using indigocarmine chromoendoscopy and lesions suspicious for invasive malignancy were excluded. The choice of endoscopic technique was made based on the Endoscopist9s judgement of best approach for each lesion. Completeness of resection was recorded. Endoscopic follow-up was performed to assess for incomplete resection or recurrence. <h3>Results</h3> 45 lesions were resected by ESD technique and 100 by EMR technique. For ESD procedures the median lesion size was 40 mm (range 20–150). 19/45 were salvage procedures post failed attempts at endoscopic resection. Endoscopic clearance was achieved at first attempt in 91% of the procedures. A further 7% were cleared in a subsequent procedure. One patient was referred for surgery for perforation and two patients went to surgery for unsuspected cancer found on histological examination of the resection specimen. At endoscopic follow-up 100% had complete clearance with no residual disease. There was one perforation requiring surgery, two microperforations (endoscopically managed), three delayed bleeds and two post polypectomy syndromes (conservatively managed) giving an overall complication rate of 18%. For the EMR cohort the median lesion size was 40 mm (range 20–100). All procedures were primary resections. Endoscopic clearance was achieved in 90% of cases. Two patients were referred for surgery for incomplete resection. In seven patients unsuspected cancer was found, all of whom were referred for surgery. At endoscopic follow-up 95% of cases had achieved complete clearance with no residual disease. There was seven delayed bleeds and one post polypectomy syndrome giving an overall complication rate of 8%. <h3>Conclusion</h3> Both EMR and ESD results in an excellent complete clearance rate. While ESD appears to result in fewer recurrences at follow-up it is associated with an increased complication rate compared to EMR, predominately due to the risk of perforation. However, it is effective in patients with previous failed attempts at resection. It should be considered as an option for difficult or scarred lesions where complete clearance with EMR could be difficult. <h3>Competing interests</h3> None declared.
Response to Letter Regarding Article, “Improvement of Peripheral Endothelial Dysfunction by Protein Tyrosine Phosphatase Inhibitors in Heart Failure”
Authors: Magali Vercauteren, Elise Remy, Corinne Devaux, Brigitte Dautreaux, Jean-Paul Henry, Fabrice Bauer, Paul Mulder, Christian Thuillez, Vincent Richard, Rob Hooft van Huijsduijnen, Agnès Bombrun
Journal: Circulation (2007)
Comparative genomic analysis of the Tribolium immune system
Authors: Zhen Zou, Jay D Evans, Zhiqiang Lu, Picheng Zhao, Michael Williams, Niranji Sumathipala, Charles Hetru, Dan Hultmark, Haobo Jiang
Journal: Genome biology (2007)

Abstract Background Tribolium castaneum is a species of Coleoptera, the largest and most diverse order of all eukaryotes. Components of the innate immune system are hardly known in this insect, which is in a key phylogenetic position to inform us about genetic innovations accompanying the evolution of holometabolous insects. We have annotated immunity-related genes and compared them with homologous molecules from other species. Results Around 300 candidate defense proteins are identified based on sequence similarity to homologs known to participate in immune responses. In most cases, paralog counts are lower than those of Drosophila melanogaster or Anopheles gambiae but are substantially higher than those of Apis mellifera . The genome contains probable orthologs for nearly all members of the Toll, IMD, and JAK/STAT pathways. While total numbers of the clip-domain serine proteinases are approximately equal in the fly (29), mosquito (32) and beetle (30), lineage-specific expansion of the family is discovered in all three species. Sixteen of the thirty-one serpin genes form a large cluster in a 50 kb region that resulted from extensive gene duplications. Among the nine Toll-like proteins, four are orthologous to Drosophila Toll. The presence of scavenger receptors and other related proteins indicates a role of cellular responses in the entire system. The structures of some antimicrobial peptides drastically differ from those in other orders of insects. Conclusion A framework of information on Tribolium immunity is established, which may serve as a stepping stone for future genetic analyses of defense responses in a nondrosophiline genetic model insect.
Effects of Gevokizumab on Glycemia and Inflammatory Markers in Type 2 Diabetes
Authors: Claudia Cavelti-Weder, Andrea Babians-Brunner, Cornelia Keller, Marc A. Stahel, Malaika Kurz-Levin, Hany Zayed, Alan M. Solinger, Thomas Mandrup-Poulsen, Charles A. Dinarello, Marc Y. Donath
Journal: Diabetes Care (2012)

OBJECTIVE Metabolic activation of the innate immune system governed by interleukin (IL)-1β contributes to β-cell failure in type 2 diabetes. Gevokizumab is a novel, human-engineered monoclonal anti–IL-1β antibody. We evaluated the safety and biological activity of gevokizumab in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS In a placebo-controlled, dose-escalation study, a total of 98 patients were randomly assigned to placebo (17 subjects) or gevokizumab (81 subjects) at increasing doses and dosing schedules. The primary objective of the study was to evaluate the safety profile of gevokizumab in type 2 diabetes. The secondary objectives were to assess pharmacokinetics for different dose levels, routes of administration, and regimens and to assess biological activity. RESULTS The study drug was well tolerated with no serious adverse events. There was one hypoglycemic event whereupon concomitant insulin treatment had to be reduced. Clearance of gevokizumab was consistent with that for a human IgG2, with a half-life of 22 days. In the combined intermediate-dose group (single doses of 0.03 and 0.1 mg/kg), the mean placebo-corrected decrease in glycated hemoglobin was 0.11, 0.44, and 0.85% after 1, 2 (P = 0.017), and 3 (P = 0.049) months, respectively, along with enhanced C-peptide secretion, increased insulin sensitivity, and a reduction in C-reactive protein and spontaneous and inducible cytokines. CONCLUSIONS This novel IL-1β–neutralizing antibody improved glycemia, possibly via restored insulin production and action, and reduced inflammation in patients with type 2 diabetes. This therapeutic agent may be able to be used on a once-every-month or longer schedule.
Update in Asthma 2005
Authors: Sally E. Wenzel, Ronina Covar
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Asthma, an enormously common illness, has been a focus of research studies, many published in the journals of the American Thoracic Society and/or American Lung Association for more than 100 yr (1). In 2005, ongoing research focused on several emerging areas, including studies on the use of biomarkers to understand the clinical phenotypes and activity of the asthma, a renewed interest in the role infections play in both acute and chronic phases of asthma, an increased appreciation of the role that structural cells play in the pathogenesis of asthma, as well as studies focusing on treatment of both pediatric and adult patients.
Deep-level diagnostic value of the rDNA-ITS region
Authors: M. A. Hershkovitz, L. A. Lewis
Journal: Molecular Biology and Evolution (1996)

The similarity of certain reported angiosperm rDNA internal transcribed spacer (ITS) region sequences to those of green algae prompted our analysis of the deep-level phylogenetic signal in the highly conserved but short 5.8S and hypervariable ITS2 sequences. We found that 5.8S sequences yield phylogenetic trees similar to but less well supported than those generated by a ca. 10-fold longer alignment from rDNA-18S sequences, as well as independent evidence. We attribute this result to our finding that, compared to 18S, the 5.8S has a higher proportion of sites subject to vary and greater among-site substitution rate homogeneity. We also determined that our phylogenetic results are not likely affected by intramolecular compensatory mutation to maintain RNA secondary structure nor by evident systematic biases in base composition. Despite historical homology, there appears to be no ITS2 primary sequence similarity shared sufficient similarity to cluster correctly on the basis of alignability. Our results indicate that groups, however, share sufficient similarity to cluster correctly on the basis of alignability. Our results indicate that ITS region sequences can diagnose organismal origins and phylogenetic relationships at many phylogenetic levels and provide a useful paradigm for molecular evolutionary study.
The Glycemic Index
Authors: David S. Ludwig
Journal: JAMA (2002)

The glycemic index was proposed in 1981 as an alternative system for classifying carbohydrate-containing food. Since then, several hundred scientific articles and numerous popular diet books have been published on the topic. However, the clinical significance of the glycemic index remains the subject of debate. The purpose of this review is to examine the physiological effects of the glycemic index and the relevance of these effects in preventing and treating obesity, diabetes, and cardiovascular disease.
Mice Lacking the p53/p63 Target Gene <i>Perp</i> Are Resistant to Papilloma Development
Authors: Michelle R. Marques, Jennifer S. Horner, Rebecca A. Ihrie, Roderick T. Bronson, Laura D. Attardi
Journal: Cancer Research (2005)

Abstract Perp is a target of the p53 tumor suppressor involved in the DNA damage-induced apoptosis pathway. In addition, Perp is a target of the p53-related transcription factor p63 during skin development, where it participates in cell-cell adhesion mediated through desmosomes. Here we test the role of Perp in tumorigenesis in a two-step skin carcinogenesis model system. We find that mice lacking Perp in the skin are resistant to papilloma development, displaying fewer and smaller papillomas than wild-type mice. Proliferation levels, apoptotic indices and differentiation patterns are similar in the skin of treated Perp-deficient and wild-type mice. Instead, impaired adhesion through aberrant desmosome assembly may explain the diminished tumor development in the absence of Perp. These studies indicate that in certain contexts, Perp is required for efficient carcinogenesis and suggest a role for intact cell-cell adhesion in supporting tumor development in these settings.
A Simple Approach to Cancer Therapy Afforded by Multivalent Pseudopeptides That Target Cell-Surface Nucleoproteins
Authors: Damien Destouches, Nicolas Page, Yamina Hamma-Kourbali, Valérie Machi, Olivier Chaloin, Sophie Frechault, Charalampos Birmpas, Panagiotis Katsoris, Julien Beyrath, Patricia Albanese, Marie Maurer, Gilles Carpentier, Jean-Marc Strub, Alain Van Dorsselaer, Sylviane Muller, Dominique Bagnard, Jean Paul Briand, José Courty
Journal: Cancer Research (2011)

Recent studies have implicated the involvement of cell surface forms of nucleolin in tumor growth. In this study, we investigated whether a synthetic ligand of cell-surface nucleolin known as N6L could exert antitumor activity. We found that N6L inhibits the anchorage-dependent and independent growth of tumor cell lines and that it also hampers angiogenesis. Additionally, we found that N6L is a proapoptotic molecule that increases Annexin V staining and caspase-3/7 activity in vitro and DNA fragmentation in vivo. Through affinity isolation experiments and mass-spectrometry analysis, we also identified nucleophosmin as a new N6L target. Notably, in mouse xenograft models, N6L administration inhibited human tumor growth. Biodistribution studies carried out in tumor-bearing mice indicated that following administration N6L rapidly localizes to tumor tissue, consistent with its observed antitumor effects. Our findings define N6L as a novel anticancer drug candidate warranting further investigation.
GPs should urge patients to focus on physical activity rather than obesity, say MPs
Authors: A. O'Dowd
Journal: BMJ (2015)

Clinicians should promote physical activity regularly to their patients rather than focus on dealing with their obesity, MPs have said.

In a report from the parliamentary Health Committee,1 MPs said that far greater emphasis was needed on physical activity independent of issues such as obesity, as evidence showed that increasing physical activity levels could have a greater effect on reducing mortality than on reducing weight. They added that the next government should prioritise prevention, health promotion, and early intervention to tackle the health inequalities and avoidable harms that arise from poor diet and physical inactivity.

In a report …
Clinical determinants of survival in patients with 5-fluorouracil- based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients
Authors: C.-H. Köhne, D. Cunningham, F. Di Costanzo, B. Glimelius, G. Blijham, E. Aranda, W. Scheithauer, P. Rougier, M. Palmer, J. Wils, B. Baron, F. Pignatti, P. Schöffski, S. Micheel, H. Hecker
Journal: Annals of Oncology (2002)
TRAIL Receptor-Selective Mutants Signal to Apoptosis via TRAIL-R1 in Primary Lymphoid Malignancies
Authors: Marion MacFarlane, Susan L. Kohlhaas, Michael J. Sutcliffe, Martin J.S. Dyer, Gerald M. Cohen
Journal: Cancer Research (2005)

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its agonistic antibodies, which are currently in early clinical trials for treating various malignancies, induce apoptosis through triggering of either TRAIL-R1 or TRAIL-R2. Based on studies using agonistic monoclonal antibodies, we recently proposed that primary chronic lymphocytic leukemic cells seem to signal apoptosis primarily through TRAIL-R1. We have now synthesized mutant forms of TRAIL specific for TRAIL-R1 or TRAIL-R2. The selectivity of these mutants to induce apoptosis in cell lines is due to selective binding to their cognate receptors resulting in apoptosis via formation of a death-inducing signaling complex. Using these mutants, we now unequivocally show that primary cells from patients with chronic lymphocytic leukemia and mantle cell lymphoma signal to apoptosis almost exclusively through TRAIL-R1. Thus, no significant therapeutic benefit can be anticipated from treating such patients with agents currently in clinical trials that signal predominantly through TRAIL-R2, such as HGS-ETR2 or Apo2L/TRAIL. Our study highlights the necessity to determine whether primary cells from a particular tumor signal via TRAIL-R1 or TRAIL-R2. Such information will provide a rational approach to optimize TRAIL therapy.
Molecular control of the implantation window
Authors: S Tabibzadeh
Journal: Human Reproduction Update (1998)

Human endometrium is the end organ of the hypothalamic-pituitary-ovarian axis. Therefore, endometrium is susceptible to changes in the cases of infertility that originate from disturbances in the normal functioning of this axis. In addition, some cases of unexplained infertility may be due to altered endometrial function. This disturbed endometrial function may originate from lesions in the molecular repertoire that are crucial to implantation. Human endometrium becomes receptive to implantation by the blastocyst within a defined period during the menstrual cycle. The duration of this so-called 'endometrial receptivity' or 'implantation' period seems to span from few days after ovulation to several days prior to menstruation. Successful implantation results from a co-ordinated series of events that would allow establishment of a timely dialogue between a receptive endometrium and an intrusive blastocyst. The members of the molecular repertoire that make endometrium receptive to implantation are gradually being recognized. Among these are the cytokines, integrins, heat shock proteins, tastin and trophinin. In addition, the expression of a second set of genes including tumour necrosis factor α (TNF-α) and ebaf, may be the appropriate signal for the closure of the 'implantation window', for making the endometrium refractory to implantation and for preparing it for the menstrual shedding.
THE OBSESSIVE-COMPULSIVE CHRONIC ALCOHOLIC
Authors: EDWARD PODOLSKY
Journal: American Journal of Psychiatry (1960)

The obsessive-compulsive chronic alcoholic is characterized by: 1. Compulsive rituals and obsessive fears. 2. Rigidly controlled emotional reactions. 3. Hypochondriacal trends. 4. Rigid perfectionism of an obsessive-compulsive quality. 5. Compulsive pseudo-attempts at suicide and homicide. 6. Compulsive doubts and vacillations. 7. With intensified fears, threats and frustrations he resorts to alcohol in an attempt to moderate these intolerable feelings, obsessive thoughts and compulsive activities. One of the objectives of therapy with the obsessive-compulsive chronic alcoholic is the strengthening of the ego, building up his self-confidence. This is so, in spite of the fact that he has feelings of omnipotence. Generally, it has to be pointed out to him that the use of his defenses may be justified in principle, although it is desirable that some of his methods could and should be modified. The object is to examine the patient's specific defenses quite minutely and their dynamics unveiled. Obviously, both therapist and patient search for more effective ways of dealing with urgent underlying problems. There should be an exhaustive discussion of the patient's hostility, and methods of channelling it along creative avenues should be undertaken. How is the complicating factor of alcoholism managed? In most of the cases the use of tranquilizers, Thorazine, Miltown, Sparine, etc., is of value in moderating the craving for alcohol. In the more severe cases Antabuse has proved very effective. In the therapeutic management of the obsessive-compulsive alcoholic it is essential to treat both the neurosis and the alcoholism. The combined psychotherapy-psychopharmacological program as above indicated has proved effective in most cases.
From hyperplasia to T cell lymphoma
Authors: N Cerf-Bensussan
Journal: Gut (2002)

Disturbances in intraepithelial lymphocyte homeostasis in coeliac disease may lead to the emergence of lymphoid malignancies

Enteropathy-type intestinal T cell lymphomas (EITCL) are a recognised complication of coeliac disease (CD).1 A recent survey confirmed that non-Hodgkin lymphomas, although rare, are the main cause of mortality in CD.2 The mechanisms favouring the development of EITCL in CD patients but not in other chronic inflammatory bowel diseases remain elusive, but mounting evidence points to a profound disturbance in intraepithelial lymphocyte (IEL) homeostasis, leading to the emergence of lymphoid malignancies. A link between IELs and EITCL was first advocated in 1988 by Spencer et al who observed that most EITCL expressed the CD103 IEL marker.3 Two complementary observations suggested that EITCL derive from a reactive T cell population present in the intestine of CD patients: thus the same T cell clonal rearrangement was detected by Murray et al in EITCL and in the adjacent non-tumoral flat mucosa,4 and by Ashton-Key et al in non-lymphomatous ulcers of ulcerative jejunitis and in lymphomas, which later developed in these patients.5 Recent work in refractory sprue (RS) provided a missing link between IELs and lymphomas in CD.

RS is a coeliac-like enteropathy, primary or secondary resistant to a strict gluten free diet (GFD). Several conditions underlie villous atrophy resistant to GFD6 (Cellier et al , …
Absence of the Pulmonary Valve
Authors: RODERICK W. CHILDERS, PATRICK C. MCCREA
Journal: Circulation (1964)

A case of the Marfan syndrome with congenital absence of the pulmonary valve, ventricular septal defect, and aneurysms of the pulmonary artery and sinus of Valsalva is described. The literature is reviewed and a classification of this rare anomaly is offered.
Long-term Clinical Outcome of Fetal Cell Transplantation for Parkinson Disease
Authors: Zinovia Kefalopoulou, Marios Politis, Paola Piccini, Niccolo Mencacci, Kailash Bhatia, Marjan Jahanshahi, Håkan Widner, Stig Rehncrona, Patrik Brundin, Anders Björklund, Olle Lindvall, Patricia Limousin, Niall Quinn, Thomas Foltynie
Journal: JAMA Neurology (2013)

<h3>Importance</h3> Recent advances in stem cell technologies have rekindled an interest in the use of cell replacement strategies for patients with Parkinson disease. This study reports the very long-term clinical outcomes of fetal cell transplantation in 2 patients with Parkinson disease. Such long-term follow-up data can usefully inform on the potential efficacy of this approach, as well as the design of trials for its further evaluation. <h3>Observations</h3> Two patients received intrastriatal grafts of human fetal ventral mesencephalic tissue, rich in dopaminergic neuroblasts, as restorative treatment for their Parkinson disease. To evaluate the very long-term efficacy of the grafts, clinical assessments were performed 18 and 15 years posttransplantation. Motor improvements gained gradually over the first postoperative years were sustained up to 18 years posttransplantation, while both patients have discontinued, and remained free of any, pharmacological dopaminergic therapy. <h3>Conclusions and Relevance</h3> The results from these 2 cases indicate that dopaminergic cell transplantation can offer very long-term symptomatic relief in patients with Parkinson disease and provide proof-of-concept support for future clinical trials using fetal or stem cell therapies.
Effect of growth hormone and glutamine on the short bowel: five years later
Authors: J S SCOLAPIO
Journal: Gut (2000)

See article on page 199 

Short bowel syndrome is a condition marked by weight, fluid, and nutrient loss in the absence of adequate small intestine length. In adults this is usually the result of surgical intestinal resection for Crohn's disease, acute bowel infarction, radiation strictures, and adhesive obstruction. Patients with a residual small bowel length of 100 cm (normal 600 cm) or less usually require parenteral nutrition for survival. Prior to the discovery of total parenteral nutrition (TPN) in 1968 by Dudrick and colleagues, patients with short bowel often died as a result of fluid and nutritional deficiency.1 2 During the past three decades we have learned that parenteral nutrition can be given in the home environment (home parenteral nutrition (HPN)) with good results.3 However, there are complications associated with long term HPN which include catheter sepsis, liver injury, and bone disease. Daily administration of HPN also requires dedication and planning …
The 10 minute clinical assessment
Authors: M. Caulfield
Journal: Gut (2010)

Edited by Knut Schroeder. . Published by Wiley Blackwell, Chichester, UK, 2010, pp 772, £39.99, hardcover. ISBN-978-1-4051-8195-2

The 10 minute clinical assessment is an ideal brief aide memoire for trainees and practising general practitioners who have a short consultation time that ranges across many different clinical …