tbuckley/cabot-search huggingface dataset:
Reduced risk of UC in families affected by appendicitis: a Danish national cohort study
Authors: Nynne Nyboe Andersen, Sanne Gørtz, Morten Frisch, Tine Jess
Journal: Gut (2016)

<h3>Objective</h3> The possible aetiological link between appendicitis and UC remains unclear. In order to investigate the hereditary component of the association, we studied the risk of UC in family members of individuals with appendicitis. <h3>Design</h3> A cohort of 7.1 million individuals was established by linkage of national registers in Denmark with data on kinship and diagnoses of appendicitis and UC. Poisson regression models were used to calculate first hospital contact rate ratios (RR) for UC with 95% CIs between individuals with or without relatives with a history of appendicitis. <h3>Results</h3> During 174 million person-years of follow-up between 1977 and 2011, a total of 190 004 cohort members developed appendicitis and 45 202 developed UC. Individuals having a first-degree relative with appendicitis before age 20 years had significantly reduced risk of UC (RR 0.90; 95% CI 0.86 to 0.95); this association was stronger in individuals with a family predisposition to UC (RR 0.66; 95% CI 0.51 to 0.83). <h3>Conclusions</h3> Individuals with a first-degree relative diagnosed with appendicitis before age 20 years are at reduced risk of UC, particularly when there is a family predisposition to UC. Our findings question a previously hypothesised direct protective influence of appendicitis on inflammation of the large bowel. Rather, genetic or environmental factors linked to an increased risk of appendicitis while being protective against UC may explain the repeatedly reported reduced relative risk of UC in individuals with a history of appendicitis.
CD49d prevails over the novel recurrent mutations as independent prognosticator of overall survival in chronic lymphocytic leukemia
Authors: M Dal Bo, P Bulian, R Bomben, A Zucchetto, F M Rossi, F Pozzo, E Tissino, D Benedetti, T Bittolo, P Nanni, I Cattarossi, E Zaina, H Chivilò, M Degan, F Zaja, G Pozzato, A Chiarenza, F Di Raimondo, M I Del Principe, G Del Poeta, D Rossi, G Gaidano, V Gattei
Journal: Leukemia (2016)
Impact of a short exposure to levofloxacin on faecal densities and relative abundance of total and quinolone-resistant Enterobacteriaceae
Authors: J. Bernard, L. Armand-Lefèvre, E. Luce, A. El Mniai, F. Chau, E. Casalino, A. Andremont, E. Ruppé
Journal: Clinical Microbiology and Infection (2016)
PTU-049 Management of dysphagia in patients with oesophageal cancer: Abstract PTU-049 Table 1
Authors: G Chadwick, O Groene, R Hardwick, T Crosby, S Riley, D Cromwell
Journal: Gut (2015)

<h3>Introduction</h3> The commonest symptom associated with oesophageal cancer is dysphagia, this is frequently managed with an oesophageal stent. A randomised trial<sup>1</sup>suggested that for patients with a life expectancy of &gt;3 months, brachytherapy may provide better symptom relief with fewer complications. But uptake appears to be low in the UK. In 2010, only 54% of Cancer Networks reported having access to brachytherapy.<sup>2</sup> This study investigated the use of these therapeutic options in England and Wales. <h3>Method</h3> The study used data from the National Oesophago-Gastric Cancer Audit, limited to patients diagnosed with oesophageal cancer between 1<sup>st</sup>April 2011 and 31<sup>st</sup>March 2013 in England and Wales, where treatment intent was palliative and patients received either brachytherapy or endoscopic stenting. We compared patient characteristics, complication rates and survival across the two groups. <h3>Results</h3> Overall 9,252 patients were included in the study. Of these 2,333 had an oesophageal stent placed, 49 had brachytherapy and 4 had both. Patient characteristics varied significantly between the two groups (Table 1). The most frequent choice of stent was covered metal (83.2%), with the majority of stents were placed under combined fluoroscopic and endoscopic control (38.2%) or endoscopic control alone (31.9%). 98.3% of stents were successfully inserted. Complication rates associated with both brachytherapy and stenting were under 2%, with no statistically significant difference. Post-intervention 90-day mortality after brachytherapy was 8.2% (95% CI 0.02–16.1%) suggesting appropriate use. But after stent insertion median survival 95 days (IQR: 42–189). This suggests some patients may have been suitable for brachytherapy. <h3>Conclusion</h3> Half of patients who had a stent inserted survived more than 3 months, these patients may have achieved better symptom control with fewer complications with brachytherapy instead.<sup>1</sup>Only 9 NHS trusts reported using brachytherapy, suggesting it is currently underutilised. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Homs MYV, Steyerberg EW, Eijkenboom WMH, <i>et al</i>. Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia from oesophageal cancer: multicentre randomised trial. Lancet 2004;364:1497–504 Groene O, Chadwick G, Riley S, <i>et al</i>. Re-organisation of oesophago-gastric cancer services in England and Wales: a follow-up assessment of progress and remaining challenges. BMC Research Notes 2014;7:24
AB0961 Can Hepatocellular Carcinoma Cause Complex Regional Pain Syndrome?
Authors: V. Yılmaz, T. Dandinoglu, M. Karadeniz, Ö. Dandin, U. Teomete
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The most common reasons of CRPS are accepted as soft tissue trauma and fractures. In addition to trauma, primary pathologies of the central nervous system and cerebrovascular diseases, malignancy would also cause CRPS as an exeptional and very rare reason. <h3>Objectives</h3> We want to emphasize and highlight an uncommon cause of CRPS and tried to raise awareness about malignancy associated CPRS. <h3>Methods</h3> A 68-year-old male patient was presented with 2 months history of pain, sweeling and numbness in the left foot. There was no history and findings of any trauma or other CRPS reasons. <h3>Results</h3> Detailed investigations including computerised tomography (CT) scan of the abdomen revealed multiple masses located in right, left and caudate lobes of the liver. Increased activity was detected in left foot by the bone scintigraphy scan with technetium 99m. Other CRPS reasons were exluded. <h3>Conclusions</h3> Malignacy associated cases may present before malignancy or as a complication of a neoplasia. Exact pathogenesis is stil unclear and further studies are needed to explore mechanisms behind malignancy associated disease. Spontaneous development of CRPS should alert the physician for the possibility of malignancy. Every patient should be assessed carefully and if needed further evaluated for the exclusion of other underlying conditions. Early diagnosis of CPRS in malignancy may help to decrease morbidity and mortality rates associated with the malignancy. <h3>Disclosure of Interest</h3> None declared
Diagnosis of airways obstruction should be based on symptoms and an FEV<sub>1</sub>/FVC ratio below the lower limit of normal
Authors: Philip H Quanjer, Irene Steenbruggen, Jan Willem van den Berg
Journal: BMJ (2016)

In their article on the diagnosis of chronic obstructive pulmonary disease (COPD) in primary care, Conway and colleagues state that the diagnosis can be confirmed by a low FEV1/FVC (forced expiratory volume in one second/forced vital capacity) ratio,1 with a ratio <0.70 confirming a diagnosis of pathological airflow limitation. The GOLD (Global Initiative for Chronic Obstructive Lung Disease) group recommended this cut-off …
Abstract 12709: Dynamics of Flow-Responsive Kinase Cε Modulates Glycolytic Metabolites to Promote Vascular Repair
Authors: Tyler Beebe, David Liem, Hilary Yen, Amirhossein Kaboodrangi, Nelson Jen, Juhyun Lee, Peng Fei, Peipei Ping, Rongsong Li, Tzung K Hsiai
Journal: Circulation (2015)

Hemodynamic shear stress has recently been reported to modulate vascular development and repair via canonical Wnt--catenin signaling pathway. It is recognized that protein Kinase C isoform epsilon (PKCε) signaling in mitochondria confers cardioprotection via VEGF and eNOS activation in response to ischemia/reperfusion injury. Here, we hypothesized that shear stress-responsive PKCε signaling modulates glycolytic metabolites to promote vascular repair. By performing a metabolomic analysis, both oscillatory (OSS: ±1 dynes·cm -2 at 1 Hz) and pulsatile shear stress (PSS: 23 dynes·cm -2 at 1 Hz) significantly increased endothelial glycolytic metabolites; namely, xylitol and dihydroxyacetone ( n =6, p &lt; 0.01 vs. control), but decreased gluconeogenic metabolites; namely, aspartic acid. Both OSS and PSS up-regulated PKCε mRNA and protein expression via VEGF receptor (n=3, p &lt; 0.05); and constitutively active PKCε increased basal glycolysis and activity by the Seahorse assay ( n =4, p &lt;0.01 vs. dominant negative PKCε control), implicating that shear stress-responsive PKCε modulates glycolysis. To recapitulate in transgenic Tg(flk1:GFP) zebrafish embryos, we performed micro-injection of GATA-1a morpholino oligonucleotide (MO) at 1-4 cell stage to inhibit hematopoeisis, thus decreasing viscosity and fluid shear stress. In response to tail amputation, GATA-1 MO impaired and delayed vascular repair compared with the control injection ( n =20, p &lt;0.01 vs. control) ( Figure 1 ). Co-injection of PKCε mRNA with GATA-1a MO rescued tail repair ( n =5, p &lt;0.05). Overall, shear stress-responsive VEGFR- PKCε signaling modulates glycolytic metabolites to influence vascular repair. Thus, hemodynamic shear stress imparts both developmental and metabolic effects to promote vascular regeneration. Figure 1. Tail repair in response to injection with GATA-1 MO or rescue by co-injection with PKCε mRNA, dpf: days post-fertilization; dpa: days post-amputation.
Cell cycle effects of the EGFR TK inhibitor erlotinib in NSCLC cell lines
Authors: Yi-He Ling, Roman Perez-Soler
Journal: Cancer Research (2005)

2284  p27KIP, a cyclin-dependent kinase (cdk) inhibitor and a putative tumor suppressor, plays a critical role in the regulation of cell proliferation and cell cycle progression. Erlotinib, an orally bioavailble EGFR tyrosine kinase inhibitor, has been shown a potential activity against cancer cell growth in vitro and in vivo. In previous work, we have reported that erlotinib exerts the inhibitory effects on EGFR high expressed human non-small cell lung cancer cell H322 through the disruption of G1 -related cell cycle regulators and blocking cell cycle progression from G1 to S phase transition. The present study shows that erlotinib arrests H322 cells at G1 phase by accumulating the p27KIP protein, and initiating a chain of events by decreasing the amounts of cyclin A and cyclin E and the suppression of cyclin A- or cyclin E-associated cdk-2 kianse activity. Erlotinib induced G1 arrest and p27KIP up-regulation in the tested sensitive cell lines (H322, H358, and A431), but to lesser degree in the resistant cell lines (A549, H596, and H1299). The G1 arrest and p27KIP up-regulation by erlotinib was sustained within 8 h of removal of drug exposure, and completely relieved at 24 h. The immunocytochemical and immunoblot studies revealed that erlotinib treatment resulted in p27KIP localization in nucleus, whereas; the p27KIP was predominately detected at cytoplasm in control cells. In addition, erlotinib treatment led to a dramatic inhibition of p27KIP phosphorylation at Thr 187, and down-regulation of Skp2 expression. As a result, the half-life of p27KIP was significantly increased by erlotinib treatment. Furthermore, the reduction of p27KIP expression using p27KIP small interfering RNA abrogated erlotinib-induced G1 phase arrest and cell growth inhibition. Taken together, the results of this study demonstrated that p27KIP as a key mediator of cell cycle plays an implant role in erlotinib-induced cell growth inhibition at G1 phase arrest. This work was supported in part by NIH grant CA50270 and OSI Pharmaceuticals.
A Peroxidase-Staining Procedure for the Identification of Polymorphonuclear Leukocytes and Leukocyte Casts in the Urinary Sediment
Authors: Michael Kaye, Hisako Watanabe
Journal: New England Journal of Medicine (1958)

THE infrequency with which a firm clinical diagnosis of pyelonephritis can be made without histologic examination of renal tissue prompted the present study. The urinary sediment might be expected to be of value in determining renal disease and the so-called pus or polymorphonuclear-leukocyte cast has been considered characteristic of active pyelonephritis. However, even with the most careful scrutiny these casts frequently cannot be identified in pyelonephritic urines by ordinary methods. Furthermore, the differentiation of the polymorphonuclear cast from one composed of renal tubular epithelial cells is often impossible. It was considered likely that if a staining method could be devised . . .
Association of hyperphosphorylated paratarg-7, the first autosomal-dominantly inherited risk factor for hematological neoplasms, with MGUS and multiple myeloma in different ethnic groups.
Authors: S. Grass, S. Iida, A. Wikowicz, N. Fadle, A. Inagaki, K. Preuss, M. Ziepert, R. Ueda, M. Pfreundschuh
Journal: Journal of Clinical Oncology (2010)

8111 Background: Hyperphosphorylated paratarg-7 (pP-7) is a frequent target of paraproteins in Caucasian patients with MGUS/MM (Preuss et al. Int J Cancer. 2009; 125:656-61). Carriers of pP-7 have an 8-times increased risk to develop IgA/IgG-MGUS and multiple myeloma (Grass et al., Lancet Oncology. 2009; 10:950-956) and a 6.5 times increased risk to develop IgM-MGUS and Waldenström's macroglobulinemia (Grass et al., Blood. 2009;114:1513s). Analysis of affected families showed that pP-7 is inherited in a dominant fashion. Thus pP-7 is the first molecularly defined autosomal-dominant risk factor for any hematological neoplasm. Because of its autosomal-dominant inheritance we investigated the prevalence of pP-7 carrier state in a Japanese population where the frequency of MGUS/MM is lower than in Europe, and compared it with that of a Caucasian population of MGUS/MM patients and healthy controls. Methods: Peripheral blood from 252 Caucasian patients with MGUS/MM and 200 healthy blood donors was analyzed for pP-7 carrier state by isoelectric focussing and for pP-7 specific antibodies by ELISA and compared with 59 Japanese MGUS/MM patients and 178 healthy Japanese controls. Results: 35/252 (13.9%) of German, but only 2/59 (3.4%) of Japanese IgA/IgG MGUS/MM patients had a pP-7 specific paraprotein (p=0.025; c2-test). The prevalence of healthy pP-7 carriers in the German population was 4/200 (2.0%), while it was only 1/178 (0.6%) in the Japanese population (p=0.376; Fisher's exact test). The relative risk for pP-7 carriers to develop MGUS/MM has an odds ratio of 7.9 (p<0.001) in the Caucasian population, while it is 6.2-fold (p=0.139) in the Japanese population. Conclusions: The fraction of pP-7 carriers with a pP-7 specific paraprotein among the patients with MGUS/MM is higher among Caucasians than Japanese patients. Nevertheless, pP-7 carrier state is associated with a similarly increased risk to develop MGUS/MM in both populations. pP-7 is the risk factor with by far the highest odds ratio to develop IgA/IgG-MGUS and multiple myeloma known to date in both ethnic groups. No significant financial relationships to disclose.
The 5000% case: a glimpse into the financial issue of lung cancer treatment
Authors: Jordi Remon, Julia Bonastre, Benjamin Besse
Journal: European Respiratory Journal (2016)

A critical issue concerning drug treatment costs was recently brought, somewhat dramatically, into the public arena accompanied by heated political debate after an unexpected overnight increase in the price of Daraprim, the only approved treatment for toxoplasmosis, which has been available for over 60 years. In August 2015, Turing Pharmaceuticals (New York, NY, USA), a start-up founded by a former hedge fund manager, acquired the drug and immediately raised the price from $13.50 a tablet to $750 [1]. For many oncologists, this unaffordable price echoed the impressive costs of many recently released cancer drugs. A new end-point in the development of cancer drugs has recently been put forward, taking this financial parameter into consideration. The term "financial toxicity" has been coined, reflecting the patient impact of the costs of cancer due to out-of-pocket expenses ( i.e. costs not covered by government or private insurance) [2]. Discrepancies in access to personalised treatment could be due to access to molecular testing and treatment costs <http://ow.ly/ZxK5v>
The ARHI tumor suppressor gene may prevent nuclear translocation of p-STAT3 by antagonizing the interaction of Ran with importin proteins
Authors: Shaoyi Huang, In Chang, Robert Luo, Zhen Lu, Robert Bast, Xiaomin Chen, Yinhua Yu
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

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ARHI is an imprinted tumor suppressor gene whose expression is frequently lost in breast and ovarian cancers. Despite homology to Ras and Rap, ARHI functions as a tumor suppressor, inhibiting tumor cell growth and motility. Our previous studies have shown that ARHI can interact with the transcription activator p-STAT3 and inhibit its nuclear translocation in human breast and ovarian cancer cells. The p-STAT3 protein requires association with other proteins for nuclear transport. We have hypothesized that ARHI interacts with one or more of these proteins. To identify proteins that interact with ARHI during translocation to the nucleus, we have performed proteomic analysis and found an association of ARHI with the importin protein(s) known to facilitate nuclear translocation. To explore this novel finding, we have purified 10 GST-importin fusion proteins (importin 7, 8, 13, β1, α1, α1 mutant, α3, α5, α6, α7). Using a GST-pull down assay, we found that ARHI strongly binds to most importins with the exception of importin 13 and an importin α1 mutant with an altered nuclear localization signal (NLS) binding domain. An ARHI-N terminal deletion mutant exhibited much less binding to all importins, suggesting that the 34 amino acid N-termianl extension of ARHI mediates importin binding. Using a similar GST pull-down assay, STAT3 protein bound only to importins β1, α1, α3, α6, and α7, but not to the other importins. Recent studies have shown that interaction of importins with the Ran protein is required to facilitate transport of other proteins into the nucleus. ARHI and Ran belong to same family of small G-proteins, suggesting that ARHI might antagonize the interaction of importins with Ran, preventing effective nuclear transport of p-STAT3. To test our hypothesis, we have constructed and purified ARHI protein and measured its effect on nuclear transport in Hela cells. ARHI protein blocked interaction of GFP-NLS and GFP-BIB (beta-like import receptor binding) fusion proteins with importin α and β, preventing their nuclear translocation. Further studies will evaluate the interaction of ARHI with Ran-importin complexes required for STAT3 nuclear transfer.
Case 35-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Robert H. Schapiro, Carolyn C. Compton
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 28-year-old woman was admitted to the hospital because of severe abdominal pain and vomiting.The patient was well until 18 months earlier, when she experienced the first of four or five bouts of severe pain in the left lower abdominal quadrant, each of which began an hour or two after eating, lasted for about one week, and was treated by intramuscular injections of an unknown medication, with relief of symptoms; the attacks occurred approximately four months apart; during one episode the patient was told that she had "colitis." She was then well during the next four . . .
Health anxiety: the silent, disabling epidemic
Authors: Peter Tyrer, Trine Eilenberg, Per Fink, Erik Hedman, Helen Tyrer
Journal: BMJ (2016)

Treatable with a range of highly effective interventions

“We are glad to say, Mr Jones, that all your test results are normal and you have nothing to fear.” Mr Jones has received this message many times after being examined for many severe diseases such as cancer, multiple sclerosis, and heart disease, which over the years he has been convinced he must have. Yet, this is the core of his problem—despite how much he would like to, he cannot do what the doctor says: stop worrying. He used to attend his general practitioner frequently to be reassured that nothing was wrong with him, but the reassurance was only short lived and then the worrying started all over again. After many years of distress, Mr Jones is embarrassed that he cannot control his health worries and preoccupation and has lately avoided contact with his GP, knowing it does not help him very much.

Mr Jones is not alone. He joins many others with health anxiety. This diagnosis is a relatively recent one that will be unfamiliar to many readers of this journal. It overlaps with hypochondriasis and the new “illness anxiety disorder”1 in the American classification DSM-5, …
TCTAP A-162 Usefulness of Routine Angiographic Evaluation to Detect Upper-Limb Artery Anomalies
Authors: Soetandar Widjaja, Hendro Adi Kuncoro, Monique Priscilla Fransiska Rotty, Yosua Arthur Iskandar, Johan Senihardja, Benny Mulyanto Setiadi, Bambang Budiono, Janry Anton Pangemanan, Agnes Lucia Panda
Journal: Journal of the American College of Cardiology (2016)
Analysis of Progression Free Survival in the New Epoc Study in an All Ras Wild-Type Population
Authors: J.A. Bridgewater, S.A. Pugh, K. Moutasim, G.J. Thomas, R. Thiébaut, F. Liebaert, S. Falk, M. Finch-Jones, J.W. Valle, D. O'reilly, A. Siriwardena, J. Hornbuckle, M. Rees, T. Iveson, T. Hickish, M. Bowers, O.J. Garden, D. Cunningham, T.S. Maughan, J.N. Primrose
Journal: Annals of Oncology (2014)