tbuckley/cabot-search huggingface dataset:
PWE-160 The Joint Hypermobility Syndrome Is Associated With Functional Dyspepsia And Reflux And Identifies A Subgroup With Somatisation, Chronic Pain And Worse Quality Of Life
Authors: A Fikree, R Aktar, A Farmer, R Grahame, C Knowles, Q Aziz
Journal: Gut (2014)

<h3>Introduction</h3> The Joint hypermobility syndrome (JHS) is a non-inflammatory connective tissue disorder with a prevalence of 20%. It is characterised by joint hypermobility,chronic pain, fibromyalgia (FM) and dysautonomia. Gastrointestinal (GI) symptoms e.g., dyspepsia, reflux, bloating and constipation are present in up to 80% of affected individuals. Small studies suggest that FGID are common in these patients yet no controlled studies have systematically investigated if JHS is associated with particular GI diagnoses nor explored the effect of JHS on non-GI symptom presentation and quality of life (QOL). <h3>Methods</h3> Using a nested case-control double-blind study in secondary care GI clinics, consecutive new referrals (without prior GI diagnosis), aged 18–70, completed validated questionnaires for GI, somatic, psychological and autonomic symptoms and QOL, and were assessed for JHS and FM. They then consulted a gastroenterologist, underwent investigations and received a GI diagnosis. ROME III criteria were used to categorise FGID. A control group of patients, aged 18–70, who were referred to secondary care for non-GI related problems, were similarly assessed. The prevalence of JHS in various GI diagnoses and in controls,adjusted for age and gender,was compared. Non-GI characteristics and QOL was compared in JHS and non-JHS patients. <h3>Results</h3> 688 GI patients [254 organic: (55% F, 43y); 341 FGID: (65% F, 40y); 53 reflux: (40% F, 46y)] and 93 non-GI controls (67% F, 43y) were included. JHS prevalence was higher in FGID (38%) and reflux (40%) compared to organic disorders (26%) and controls (26%) (p = 0.003). JHS was significantly associated with FGID (ORadj: 1.7, CI:1.02–2.88), specifically postprandial distress syndrome (ORadj 2.2, CI: 1.2–2.2), and with reflux disorders (ORadj 2.2, CI: 1.1–4.7), but not with organic disorders (ORadj: 1.0, CI:0.6–1.8). FGID patients with JHS had significantly more FM (12.6 vs. 4.9%, p = 0.02), chronic pain (23.2 vs. 11.7%, p = 0.01), somatisation scores (13 vs. 10, p &lt; 0.01), anxiety scores (0.5 vs. 0.36, p = 0.02) and urinary autonomic symptoms (30.5% vs 19.6%, p = 0.047), and worse pain related QOL scores (45 vs. 63.5, p &lt; 0.01). <h3>Conclusion</h3> JHS is associated with functional dyspepsia, and non-erosive reflux disease, and with FM, chronic pain, somatisation and anxiety. Clinical assessment for JHS in GI clinics is indicated in those with a combination of functional upper GI symptoms and extra-intestinal symptoms as this may help earlier identification of a more ‘challenging’ group of patients with multiple somatic symptoms and worse QOL. These may benefit from early multidisciplinary approach involving rheumatologists and pain specialists. <h3>Disclosure of Interest</h3> None Declared.
International Pediatric Non-Hodgkin Lymphoma Response Criteria
Authors: John T. Sandlund, R. Paul Guillerman, Sherrie L. Perkins, C. Ross Pinkerton, Angelo Rosolen, Catherine Patte, Alfred Reiter, Mitchell S. Cairo
Journal: Journal of Clinical Oncology (2015)

Response criteria are well established for adult patients with non-Hodgkin lymphoma (NHL). A revised set of response criteria in adults with NHL was recently published. However, NHL in children and adolescents involves different histologies, primary sites of disease, patterns of metastatic spread, approaches to therapy, and responses to treatment compared with adult NHL. However, there are no standardized response criteria specific to pediatric NHL. Therefore, we developed international standardized methods for assessing response to therapy in children and adolescents with NHL.An international multidisciplinary group of pediatric oncologists, pathologists, biologists, and radiologists convened during and after the Third and Fourth International Childhood, Adolescent and Young Adult NHL Symposia to review existing response and outcome data, develop methods for response evaluation that reflect incorporation of more sensitive technologies currently in use, and incorporate primary and metastatic sites of disease for the evaluation of therapeutic response in children and adolescents with NHL.Using the current adult NHL response criteria as a starting point, international pediatric NHL response criteria were developed incorporating both contemporary diagnostic imaging and pathology techniques, including novel molecular and flow cytometric technologies used for the determination of minimal residual disease.Use of the international pediatric NHL response criteria in children and adolescents receiving therapy for NHL incorporates data obtained from new and more sensitive technologies that are now being widely used for disease evaluation, providing a standardized means for reporting treatment response.
Women in Medicine: Two Points of View I. The Future of Women Physicians
Authors: E. Grey Dimond
Journal: JAMA (1983)

I HAVE been carrying on a woman-man dialogue with a colleague of mine who is a woman. Although the number of women in medical schools now constitutes almost one third of students, and at the University of Missouri, Kansas City, it is 45%, my female colleague continues to charge us (the men) with sexism and is convinced that women physicians have not truly achieved equality. Recently, she sent me a note telling me that the problem was that society continued to have certain expectations of women, and even though we men claim that women have achieved equality, we act toward women in medicine in such a way that the women respond by playing back to our expectations and thus entrap themselves. That expectation repeats the housekeeper image, the stove-and-diaper-tending image, and women remain trapped because of this social expectation. The fact is that in the field of medicine, the significant
EMMPRIN promotes angiogenesis through hypoxia-inducible factor-2α–mediated regulation of soluble VEGF isoforms and their receptor VEGFR-2
Authors: Faten Bougatef, Cathy Quemener, Sabrina Kellouche, Benyoussef Naïmi, Marie-Pierre Podgorniak, Guy Millot, Eric E. Gabison, Fabien Calvo, Christine Dosquet, Céleste Lebbé, Suzanne Menashi, Samia Mourah
Journal: Blood (2009)
CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy
Authors: Animesh Pardanani, Rhett P. Ketterling, Stephanie R. Brockman, Heather C. Flynn, Sarah F. Paternoster, Brandon M. Shearer, Terra L. Reeder, Chin-Yang Li, Nicholas C. P. Cross, Jan Cools, D. Gary Gilliland, Gordon W. Dewald, Ayalew Tefferi
Journal: Blood (2003)
Clinical impact and predisposing factors of delayed-onset neutropenia after autologous hematopoietic stem-cell transplantation for B-cell non-Hodgkin lymphoma: association with an incremental risk of infectious events
Authors: H Kato, K Yamamoto, K Matsuo, Y Oki, H Taji, Y Kuwatsuka, M Seto, Y Kagami, Y Morishima
Journal: Annals of Oncology (2010)
Retraction of the Research Article: "CD4 <sup>+</sup> T cell autoimmunity to hypocretin/orexin and cross-reactivity to a 2009 H1N1 influenza A epitope in narcolepsy"
Authors: Alberto K. De la Herrán-Arita, Birgitte Rahbek Kornum, Josh Mahlios, Wei Jiang, Ling Lin, Tieying Hou, Claudia Macaubas, Mali Einen, Giuseppe Plazzi, Catherine Crowe, Evan W. Newell, Mark M. Davis, Elizabeth D. Mellins, Emmanuel Mignot
Journal: Science Translational Medicine (2014)

Post date 30 July 2014

We, the authors of the Research Article “CD4+ T Cell Autoimmunity to Hypocretin/Orexin and Cross-Reactivity to a 2009 H1N1 Influenza A Epitope in Narcolepsy” ([ 1 ][1]), have been unable to reproduce the key findings reported in the paper. Specifically, we cannot demonstrate a differential ELISpot response of CD4+ T cells from patients with narcolepsy compared to those from normal controls after exposure to the hypocretin peptides HCRT56–68 or HCRT87–99. Because the validity of the conclusions reported in the study cannot be confirmed, we are retracting the article.

1.  [↵][2]1.   A. K. De la Herran-Arita,     2.   B. R. Kornum,     3.   J. Mahlios,     4.   W. Jiang,     5.   L. Lin,     6.   T. Hou,     7.   C. Macaubas,     8.   M. Einen,     9.   G. Plazzi,     10.  C. Crowe,     11.  E. W. Newell,     12.  M. M. Davis,     13.  E. D. Mellins,     14.  E. Mignot
        , CD4+ T cell autoimmunity to hypocretin/orexin and cross-reactivity to a 2009 H1N1 influenza A epitope in narcolepsy. Sci. Transl. Med. 5, 216ra176 (2013). doi:10.1126/scitranslmed.3007762 pmid:24353159
        [OpenUrl][3][Abstract/FREE Full Text][4]

 [1]: #ref-1
 [2]: #xref-ref-1-1 View reference 1 in text
 [3]: {openurl}?query=rft.jtitle%253DScience%2BTranslational%2BMedicine%26rft.stitle%253DSci%2BTransl%2BMed%26rft.issn%253D1946-6234%26rft.aulast%253DDe%2Bla%2BHerran-Arita%26rft.auinit1%253DA.%2BK.%26rft.volume%253D5%26rft.issue%253D216%26rft.spage%253D216ra176%26rft.epage%253D216ra176%26rft.atitle%253DCD4%252B%2BT%2BCell%2BAutoimmunity%2Bto%2BHypocretin%252FOrexin%2Band%2BCross-Reactivity%2Bto%2Ba%2B2009%2BH1N1%2BInfluenza%2BA%2BEpitope%2Bin%2BNarcolepsy%26rft_id%253Dinfo%253Adoi%252F10.1126%252Fscitranslmed.3007762%26rft_id%253Dinfo%253Apmid%252F24353159%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx
 [4]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTE6InNjaXRyYW5zbWVkIjtzOjU6InJlc2lkIjtzOjE0OiI1LzIxNi8yMTZyYTE3NiI7czo0OiJhdG9tIjtzOjMwOiIvc2NpdHJhbnNtZWQvNi8yNDcvMjQ3cnQxLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==
Competition between Transposable Elements and Mutator Genes in Bacteria
Authors: T. Feher, B. Bogos, O. Mehi, G. Fekete, B. Csorgo, K. Kovacs, G. Posfai, B. Papp, L. D. Hurst, C. Pal
Journal: Molecular Biology and Evolution (2012)

Although both genotypes with elevated mutation rate (mutators) and mobilization of insertion sequence (IS) elements have substantial impact on genome diversification, their potential interactions are unknown. Moreover, the evolutionary forces driving gradual accumulation of these elements are unclear: Do these elements spread in an initially transposon-free bacterial genome as they enable rapid adaptive evolution? To address these issues, we inserted an active IS1 element into a reduced Escherichia coli genome devoid of all other mobile DNA. Evolutionary laboratory experiments revealed that IS elements increase mutational supply and occasionally generate variants with especially large phenotypic effects. However, their impact on adaptive evolution is small compared with mismatch repair mutator alleles, and hence, the latter impede the spread of IS-carrying strains. Given their ubiquity in natural populations, such mutator alleles could limit early phase of IS element evolution in a new bacterial host. More generally, our work demonstrates the existence of an evolutionary conflict between mutation-promoting mechanisms.
Dual effects of norepinephrine and mechanisms of baroreceptor stimulation.
Authors: P A Munch, P N Thoren, A M Brown
Journal: Circulation Research (1987)

The aim of this study was to determine the mechanism of action of norepinephrine (NE) on arterial baroreceptors (BRs), with the focus on regularly discharging, presumably myelinated fibers. With the use of an in vitro aortic arch/aortic nerve preparation from rats, BR single-fiber discharge was recorded simultaneously with aortic pressure and diameter. At constant suprathreshold pressure, NE had two dose-dependent effects. Inhibition was produced at low concentrations (10(-10)-10(-7) M), whereas excitation was produced at high concentrations (10(-6)-10(-5) M). Inhibition was attributed to BR unloading since the response was consistent with the fall in diameter, was mimicked by angiotensin II (10(-10)-10(-6) M), and was prevented by pretreatment with the smooth muscle relaxant sodium nitroprusside (10(-6) M) or the selective alpha 1-adrenergic antagonist, prazosin (10(-6) M). Excitation was attributed to direct activation of the BR endings since this response was independent of changes in diameter, was not mimicked by angiotensin II, and was not prevented by sodium nitroprusside but was blocked by prazosin. These results indicate that NE has two modes of action, one mediated by contraction of local vascular smooth muscle and the other due to direct excitation of the nerve endings. It was also found that BR discharge at given diameters decreased more when pressure was lowered (smooth muscle passive) than when the aorta constricted (smooth muscle active). Furthermore, if diameter was held constant during smooth muscle contraction, discharge increased, as opposed to decreasing at constant pressure. These later results suggest that BR responses to vasoactive agents reflect not only changes in wall dimension but perhaps changes in wall tension and/or the coupling relation between BR and smooth muscle structures.
Liste d'attente? Pourquoi?
Authors: John Petri
Journal: BMJ (2007)

Doctor, when can I have my operation?”

“Well, my dear, in a few weeks I suppose.” I was learning fast.

I walked into my first UK consultant job from a similar job in France 13 years ago. At first my patients were easy to please, because there was no waiting list in my orthopaedic firm. But I can take no credit for this, because mine was a newly created job, and at first I had to steal patients from colleagues to have something to do. Otherwise, however, waiting lists were omnipresent and, apparently, an unavoidable fact of life. Still, how unavoidable could they be? I had had no waiting list in France. In fact I had to translate from English to explain to my French wife what it meant: “Liste d'attente.” She knew you could get stuck on a liste d'attente while desperately trying to reach a representative of the French bureaucracy over the phone, but a surgical liste d'attente? She was horrified.

I was determined not to allow a waiting list to form. I thought, “I'll show them how I can organise an efficient service and get operations done at the same rate as I see patients in clinic.” How naive I was. Within two years I was operating on people who had been on the list for a …
Genetic Mapping of a Third Li-Fraumeni Syndrome Predisposition Locus to Human Chromosome 1q23
Authors: Linda L. Bachinski, Shodimu-Emmanuel Olufemi, Xiaojun Zhou, Chih-Chieh Wu, Linwah Yip, Sanjay Shete, Guillermina Lozano, Christopher I. Amos, Louise C. Strong, Ralf Krahe
Journal: Cancer Research (2005)

Abstract Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous inherited cancer syndrome. Most cases (∼70%) identified and characterized to date are associated with dominantly inherited germ line mutations in the tumor suppressor gene TP53 (p53) in chromosome 17p13.1. In a subset of non-p53 patients with LFS, CHEK2 in chromosome 22q11 has been identified as another predisposing locus. Studying a series of non-p53 LFS kindred, we have shown that there is additional genetic heterogeneity in LFS kindred with inherited predisposition at loci other than p53 or CHEK2. Using a genome-wide scan for linkage with complementing parametric and nonparametric analysis methods, we identified linkage to a region of approximately 4 cM in chromosome 1q23, a genomic region not previously implicated in this disease. Identification ofa third predisposing gene and its underlying mutation(s) should provide insight into other genetic events that predispose to the genesis of the diverse tumor types associated with LFS and its variants.
Transforming Growth Factor-β and the Immune Response to Malignant Disease
Authors: Beverly A. Teicher
Journal: Clinical Cancer Research (2007)

Abstract Transforming growth factor-β (TGF-β) is a key player in malignant disease through its actions on host tissues and cells. Malignant cells often secrete large amounts of TGF-β that act on nontransformed cells present in the tumor mass as well as distal cells in the host to suppress antitumor immune responses creating an environment of immune tolerance, augmenting angiogenesis, invasion and metastasis, and increasing tumor extracellular matrix deposition. Cells of the innate immune system contribute to the high concentrations of TGF-β found in tumor masses. In addition, dendritic cell subpopulations secreting TGF-β contribute to the generation of regulatory T cells that actively inhibit the activity of other T cells. Elevated levels of plasma TGF-β are associated with advanced stage disease and may separate patients into prognostically high-risk populations. Anti–TGF-β therapy could reverse the immunosuppressive effects of this cytokine on the host as well as decrease extracellular matrix formation, decrease angiogenesis, decrease osteolytic activity, and increase the sensitivity of the malignant cells to cytotoxic therapies and immunotherapies. Phase I clinical trials of an inhibitor of TGF-β receptor type I kinase activity and a TGF-β neutralizing antibody are under way.
Glycemic and Risk Factor Control in Type 1 Diabetes
Authors: Katarina Eeg-Olofsson, Jan Cederholm, Peter M. Nilsson, Soffia Gudbjörnsdóttir, Björn Eliasson
Journal: Diabetes Care (2007)

This study was designed to investigate the clinical characteristics of a large type 1 diabetic population and to evaluate the degree of fulfillment of recently updated treatment goals.The Swedish National Diabetes Register was initiated in 1996 as a tool for quality assurance in diabetes care. A1C levels, treatment, and risk factors were analyzed in two cross-sectional samples of 9,424 patients in 1997 and 13,612 patients in 2004 and in a smaller longitudinal sample from 1997 to 2004.Mean A1C decreased from 8.2 +/- 1.3% in 1997 to 8.0 +/- 1.2% in 2004 (P < 0.001). The proportion of patients reaching A1C <7.0% increased from 17.4 to 21.2% in 2004. A slow but significant improvement in blood pressure levels was seen, but only 61.3% reached the blood pressure goal of <130/80 mmHg in 2004. Lipid control improved, and the use of lipid-lowering drugs increased. Among patients treated with lipid-lowering agents, 38% reached the goal of total cholesterol <4.5 mmol/l, and 48% reached the goal of LDL cholesterol <2.5 mmol/l. Successful long-term glycemic and blood pressure control were both independently predicted by low BMI and the absence of microalbuminuria in 1997.In this large cohort of type 1 diabetic patients, there was a slow improvement in glycemic and risk factor control from 1997 to 2004, although the gap between the clinical results and current Swedish and American treatment goals is still unsatisfactory. It is crucial that additional measures be taken to improve risk factor control in type 1 diabetic patients.
Tratamiento de las Enfermedades Reumaticas
Authors: A. St. J. Dixon
Journal: Annals of the Rheumatic Diseases (1972)

Annals of the Rheumatic Diseases shared by 69 authors, and are divided into 70 chapters, most of which have a lengthy up-to-date (1969) list of references, surveying, unlike some North American productions, the European as well as the North and South American literature.Except for a few indifferent colour plates, it is well illustrated with diagrams and photographs and covers the same general field as the textbooks by Copeman and by Hollander.Of interest to
Glove-powder peritonitis.
Authors: D F Nash
Journal: BMJ (1973)

from the urethra grew no pathogen.He made a full recovery when treated with benzyl penicillin 1 mega unit intramuscularly six hourly.His wife, who was without symptoms at this time, eventually agreed to be examined.She had cervicitis without erosion but no clinical evid- ence of urthritis.Cultures, however, grew the gonococcus from both sites.This family demonstrates once again the well-known latency of gonorrhoea in women, and it also seems very likely that the condition had remained latent in the husband until septicaemia ensued though no proof of this can be obtained The most unusual find- ing was the development of one of the rarest of the complications of gonorrhoea- namely, gonococcal septicaemia in both hus- band and wife.We have not been able to find a similar example recorded in the literature.-Weare, etc.,
Bronchial epithelial cell B7-1 and B7-2 mRNA expression after lung transplantation: a role in allograft rejection?
Authors: A. Elssner, F. Jaumann, W-P. Wolf, M. Schwaiblmair, J. Behr, H. Fürst, H. Reichenspurner, J. Briegel, J. Niedermeyer, C. Vogelmeier
Journal: European Respiratory Journal (2002)

Obliterative bronchiolitis is commonly interpreted as chronic rejection and involves the bronchial and bronchiolar epithelium. Upregulation of major histocompatibility complex (MHC) II on bronchial epithelial cells (BEC) had been hypothesised to be an important trigger of a bronchus directed rejection response. More recently, the additional expression of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) on antigen presenting cells were found to play an important role in the activation of T-lymphocytes in transplant rejection. The role of the expression of these molecules by BEC is unclear. BEC obtained by bronchial brushing and bronchoalveolar lavage fluid (BALF) cells from lung transplant recipients were studied and evaluated for messenger ribonucleic acid (mRNA) expression of B7-1 and B7-2 by semi-quantitative reverse transcriptase-polymerase chain reaction. Significantly elevated B7-1/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ratios were found in BEC from patients examined during the first 3 months after lung transplantation. Interestingly, in a small group of patients with bronchiolitis obliterans syndrome the B7-1/GAPDH and B7-2/GAPDH ratios were significantly elevated for BEC, whereas no differences were found for the BALF cells. In summary, B7 messenger ribonucleic acid expression by bronchial epithelial cells may play a role in (chronic) lung allograft rejection.
"Viral deja vu" elicits organ-specific immune disease independent of reactivity to self
Authors: D. Merkler
Journal: Journal of Clinical Investigation (2006)

Autoimmune diseases are often precipitated by viral infections. Yet our current understanding fails to explain how viruses trigger organ-specific autoimmunity despite thymic tolerance extending to many nonlymphohematopoietic self antigens. Additionally, a key epidemiological finding needs to be explained: In genetically susceptible individuals, early childhood infections seem to predispose them to multiple sclerosis (MS) or type 1 diabetes years or even decades before clinical onset. In the present work, we show that the innate immune system of neonatal mice was sufficient to eliminate an attenuated lymphocytic choriomeningitis virus (LCMV) from most tissues except for the CNS, where the virus persisted in neurons (predisposing virus). Virus-specific cytotoxic T cells (CTLs) were neither deleted nor sufficiently primed to cause disease, but they were efficiently triggered in adulthood upon WT LCMV infection (precipitating virus). This defined sequence of viral infections caused severe CNS inflammation that was histomorphologically reminiscent of rasmussen encephalitis, a fatal human autoimmune disease. Yet disease in mice was mediated by antiviral CTLs targeting an epitope shared by the precipitating virus and the predisposing virus persisting in neurons (déjà vu). Thus the concept of “viral déjà vu” demonstrates how 2 related but independently encountered viral infections can cause organ-specific immune disease without molecular mimicry of self and without breaking self tolerance.