tbuckley/cabot-search huggingface dataset:
AB0215 Risk markers of morphometric vertebral fracture in rheumatoid arthritis
Authors: C. Méndez, L. Silva, J. L. Andreu, L. Muñoz, I. Ortiz, B. García, C. Sangüesa, C. Barbadillo, J. Sanz, M. Fernández, J. Campos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoporosis is a well-known comorbidity in patients with rheumatoid arthritis (RA). A high percentage of patients with RA have low bone mineral density in axial and peripheral skeleton, which confers an increased fracture risk. In its further development, other risk factors such as age, menopause, disease activity and, especially, some of the drugs used for RA treatment, are involved. <h3>Objectives</h3> To study the prevalence of morphometric vertebral fractures (MVF) in a cohort of patients with RA and to identify demographic, analytical, densitometric and RA-related risk markers for vertebral fractures. <h3>Methods</h3> A cross-sectional cohort study in routine clinical practice conditions was designed. All patients fulfilled the ACR 2010 classification criteria for RA. We performed a questionnaire of fracture risk factors, an analytical study including serological bone markers (Procollagen Type I Intact N-terminal Propedtide and b-Cross Laps) and a hip and thoracolumbar spine bone densitometry. Patients filled out the Health Assessment Questionnaire (HAQ) and DAS28 was calculated. MVF was defined as a reduction of at least 20% in vertebral body height. A univariate analysis was performed using the presence of MVF as the dependent variable. Statistical significance was established by t-Student (parametric variables) and Mann-Whitney (nonparametric variables) tests. We considered significant a p &lt;0.05. <h3>Results</h3> We included 78 patients (77% women, mean age 59 years, duration of RA: 10 years). Vertebral fractures were found in 11 patients (14%). The presence of MVF was associated with a higher mean age (74 vs. 56, p &lt;0.05) and a long-term disease (17 vs. 9 years, P = 0.013). Bisphosphonate therapy was associated with MVF, probably reflecting an indication bias. No association with HAQ score, DAS28 or its individual components was found. We did not find any association with serological bone markers. however, vitamin D levels were significantly higher among patients with fracture (60 nm / l vs. 47 nm / l, P = 0.032) and in patients who were receiving vitamin D supplements (23% vs. 6%, p &lt;0.05). Densitometric osteopenia and osteoporosis at lumbar spine or femoral neck were significantly associated with vertebral fracture. <h3>Conclusions</h3> Around 15% of patients with RA may develop MVF. Age, duration of RA, densitometric osteoporosis, vitamin D levels, vitamin D supplements and bisphosphonates are associated with such fractures. <h3>Disclosure of Interest</h3> None Declared
Mesenteric Ischemia Mimicking ST-Segment Elevation Myocardial Infarction
Authors: Yen-Ting Yeh, Chung-Ming Tu, Yen-Wen Wu
Journal: New England Journal of Medicine (2015)

A 61-year-old man presented with epigastric pain and inferior ST-segment elevation on ECG. Angiography revealed only a 70% stenosis in a branch of the left anterior descending coronary artery. CT showed ischemic colitis, which was confirmed on laparotomy with right hemicolectomy.
Nano-zymography Using Laser-Scanning Confocal Microscopy Unmasks Proteolytic Activity of Cell-Derived Microparticles
Authors: Aurélien Briens, Maxime Gauberti, Jérôme Parcq, Joan Montaner, Denis Vivien, Sara Martinez de lizarrondo
Journal: Theranostics (2016)

Cell-derived microparticles (MPs) are nano-sized vesicles released by activated cells in the extracellular milieu.They act as vectors of biological activity by carrying membrane-anchored and cytoplasmic constituents of the parental cells.Although detection and characterization of cell-derived MPs may be of high diagnostic and prognostic values in a number of human diseases, reliable measurement of their size, number and biological activity still remains challenging using currently available methods.In the present study, we developed a protocol to directly image and functionally characterize MPs using high-resolution laser-scanning confocal microscopy.Once trapped on annexin-V coated micro-wells, we developed several assays using fluorescent reporters to measure their size, detect membrane antigens and evaluate proteolytic activity (nano-zymography).In particular, we demonstrated the applicability and specificity of this method to detect antigens and proteolytic activities of tissue-type plasminogen activator (tPA), urokinase and plasmin at the surface of engineered MPs from transfected cell-lines.Furthermore, we were able to identify a subset of tPA-bearing fibrinolytic MPs using plasma samples from a cohort of ischemic stroke patients who received thrombolytic therapy and in an experimental model of thrombin-induced ischemic stroke in mice.Overall, this method is promising for functional characterization of cell-derived MPs.
1372 THE EFFICACY OF PROBIOTICS (LACTOBACILLUS SUBTILIS/STREPTOCOCCUS FAECIUM) IN PATIENTS WITH ALCOHOLIC HEPATITIS
Authors: K.T. Suk, S.H. Park, Y.D. Kim, G.J. Cheon, D.H. Choi, M.Y. Kim, S.K. Baik, D.J. Kim
Journal: Journal of Hepatology (2012)
Case 72-1961
Journal: New England Journal of Medicine (1961)

Presentation of Case An eighteen-year-old boy entered the hospital because of pain and swelling in the right buttock. Two years previously the patient fell while ice skating, striking the right sacral region, which was tender for a few days. Nine months later he backed into an open door and struck the same area, with subsequent pain and tenderness. One year before admission progressive swelling began in the right buttock. He remained physically active and was again struck in the same area once or twice. It became exquisitely tender, interfering with sleep, and walking began to increase the pain. Transient pains . . .
EUS-FNA for patients with lymphadenopathy suspected of having recurrent malignancy after radical treatment
Authors: I Yasuda, T Ohnishi, T Mukai, M Enya, T Iwashita, T Yamada, T Takami, E Tomita, H Moriwaki
Journal: Endoscopy (2006)

Introduction: The diagnosis of lymphadenopathy after radical treatment of malignancy is sometimes difficult, especially in patients without local recurrence and without increasing serum levels of related tumor markers. Invasive surgical procedures are sometimes requested to confirm or deny the recurrence; otherwise, patients were followed by imaging tests and a very carefully monitored clinical course. Aims: To evaluate the yield of EUS-FNA in patients with mediastinal, intraabdominal, and pelvic lymphadenopathy after radical treatment of malignancy. Methods: Consecutive patients with mediastinal, intraabdominal, and pelvic lymphadenopathy after radical treatment of malignancy who were referred to our hospital between October 2003 and December 2005 were enrolled in this study. Inclusion criteria were as follows: 1) The lymph nodes (LNs) were located at sites that could be approached from the esophagus, stomach, duodenum, or rectum based on CT imaging, and 2) Local recurrence at the prior lesion was not observed on imaging tests. If patients had other lesions that were approached more easily, for example superficial LNs, these patients were excluded from this study and a sampling was performed at that site. Results: Thirty patients were included, and the locations of the LNs were mediastinum (9), intra-abdominal (19), and pelvic (2). Prior malignancy was gastric (5), lung (5), bile duct (3), uterus (2), breast (2), rectal (2), ovarial (1), colonic (1), renal (1), bladder (1), lingual (1), pancreatic cancer (1), liver cystadenocarcinoma (1), pancreatic endocrine tumor (1), Paget's disease (1), and lymphoma (2). The median period after the treatment was 23 months (range: 3–180 months). A related tumor marker was increased in only one patient (3%). From the pathological findings of the FNA sample, 14 paients were confirmed to have recurrence of a prior malignancy, 9 patients were shown to have no recurrence or other malignancies, and the remaining 6 patients were diagnosed as having different new malignancies as follows: lymphoma (4), LN metastasis from GIST of the small intestine (1), and bile duct cancer (1). One of the 9 patients shown not to have malignancy was diagnosed with recurrence by open laparotomy later. The remaining 8 patients have been observed every 3 months; the median duration of follow-up to date is 12 months (range: 6–22 months), and no increase in size or no other changes have been detected on CT. The sensitivity, specificity, and accuracy were 95%, 100%, and 97%, respectively. EUS-FNA contributed to the decisions about treatment in 29 cases (97%). No serious complications occurred related to the use of EUS-FNA. Conclusions: EUS-FNA in diagnosis of lymphadenopathy after the radical treatment of malignancy is safe, less invasive than surgical procedures, and convenient, and it has a high diagnostic value.
Abstract 5429: Cytotoxicity of AOH compounds targeting the interaction of caPCNA and its binding partners in human cancer cells
Authors: Fei Shen, Robert Hickey, Jasmine Kamran, Shanna Smith, Elizabeth Phipps, Linda Malkas
Journal: Cancer Research (2011)

Abstract Previously we reported the identification of an acidic isoform of proliferating cell nuclear antigen (caPCNA) in various cancer cells. Proliferating Cell Nuclear Antigen (PCNA) interacts with multiple binding partners to carry out vital cellular processes including DNA replication, DNA damage repair, and cell-cycle progression. We hypothesize that caPCNA performs similar functions specifically in cancer cells and, therefore, disrupting interactions of caPCNA with its binding partners will prevent necessary cellular functions, resulting in cytotoxicity to cancer cells. AOH compounds were generated based on a focused computer molecular “docking” search for small molecules that specifically targeted the interaction of caPCNA and its binding partner FEN1. MTT assays suggest that several AOH compounds have promising anti-proliferation effects in human breast and pancreatic cancer cells with EC50 values as low as or less than 10uM (lead compounds). To further evaluate the cytotoxicity of lead AOH compounds, clonogenic survival assays were performed in MCF-7 cells treated with the small molecules for 2 hours. Results showed that AOH compounds induced cytotoxicity in cancer cells in a dose-dependent manner. The IC50s of these compounds were between 10 to 20uM in MCF-7cells. To investigate the effects of the AOH compounds on DNA replication and the cell cycle, in vitro SV40 DNA replication assays and flow cytometric analysis were performed. The G2/M phase cell population was increased from 8% to 30-80% in MCF-7 cells treated with 25uM AOH compounds for 48 hours, indicating an induction of G2 arrest. AOH compound at 10uM inhibited in vitro DNA replication in malignant cell extracts by 70-80% relative to untreated correspondent cell extracts. Taken together, the potent cytotoxicity of AOH compounds in cancer cells is correlated with their inhibition of DNA replication and induction of cell cycle arrest. The compounds may be useful in the future for clinical cancer chemotherapy as a single anticancer agent and/or in combination with other anti-neoplastic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5429. doi:10.1158/1538-7445.AM2011-5429
Junior doctors’ contract and equality analysis are published
Authors: Abi Rimmer
Journal: BMJ (2016)

A new contract for junior doctors in England has been published by NHS Employers.

The Department of Health has also published an equality analysis of the contract, which found that it was “fair and justified.”

Following a breakdown of negotiations with the BMA, health secretary Jeremy Hunt announced in February that the government would impose a new contract on junior doctors from August this year.1

The new contract, published on Thursday 31 March, sets out the terms and conditions for junior doctors.2 NHS Employers, which developed the contract on behalf of the health department, said that implementation of the contract would be phased.

It said that most doctors in training would be moved on to the 2016 contract over an 18 month period, starting in August 2016. This would be linked to when their current …
Endoscopic removal of a 35-mm fish bone totally embedded in the gastric wall
Authors: José Rodrigues, Pedro Barreiro, Liliana Carvalho, Maria Túlio, Cristina Chagas
Journal: Endoscopy (2016)

A 61-year-old woman with no relevant medical history attended the emergency department with a 3-day history of epigastric pain and fever, and reports of fish bone ingestion 6 days earlier. No signs of peritoneal irritation were found during abdominal examination. The patient underwent an abdominal computed tomography scan, which revealed a gastric wall thickening with a radiodense linear foreign body embedded in the wall, associated with mesenteric stranding but no free air. Upper endoscopy was performed and showed a 12-mm subepithelial bulge covered with congested mucosa in the gastric antrum ([Fig. 1]). Using a biopsy forceps, multiple biopsies were taken from the overlying mucosa, exposing the tip of the foreign body ([Fig. 2]).
Primary combined adenoid cystic carcinoma, basaloid squamous cell carcinoma, and squamous cell carcinoma of the esophagus
Authors: T. Terada
Journal: Endoscopy (2012)

Reports of adenoid cystic carcinoma and basaloid squamous cell carcinoma of the esophagus are rare [1] [2] [3] [4], while esophageal combined carcinoma is very rare [5]. Most cases of combined carcinoma of the esophagus consist of squamous cell carcinoma, adenocarcinoma, and small cell carcinoma [5]. This is the first report of combined adenoid cystic carcinoma, basaloid squamous cell carcinoma, and squamous cell carcinoma of the esophagus.
Detection of Heterozygotes for Recessive von Willebrand's Disease by the Assay of Antihemophilic-Factor-like Antigen
Authors: Jan J. Veltkamp, Nico H. van Tilburg
Journal: New England Journal of Medicine (1973)

Asymptomatic relatives of a girl with an extremely severe form of von Willebrand's disease who had consanguineous parents were investigated to determine whether they carried the von Willebrand gene. Bleeding time, procoagulant antihemophilic-factor activity (one-stage method), and antihemophilic-factor-like antigen level (quantitative immunoelectrophoresis) and antibody-neutralizing capacity were estimated in 22 relatives. All showed normal antihemophilic-factor procoagulant activity, but five had significantly low levels of antihemophilic-factor-like antigen. Comparison of the levels of antigen and antihemophilic-factor activity (on the basis of a regression analysis) made it possible to identify three additional carriers of this von Willebrand gene. These results suggest that the antigen is more directly related to the primary gene-product of the von Willebrand locus than antihemophilic-factor activity. (N Engl J Med 289:882–885, 1973)
Horseshoe Kidney Incidentally Revealed on Meckel Scintigraphy
Authors: Xia Bai, Ion Codreanu, Hua Yang, Sabah Servaes, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2015)

An 8-year-old male patient with history of bloody stools underwent a Meckel diverticulum scintigraphy to evaluate for ectopic gastric mucosa. The static images showed 2 abnormal foci of radiotracer accumulation in the mid-abdomen. Contrary to the renal activity, the foci appeared more prominent on the anterior view and localized anteriorly to the expected kidneys location on the left lateral view. Carefully reviewed dynamic acquisition revealed faint catenary-shaped activity in this region on earlier images, gradually evolving into 2 prominent foci on later images. A horseshoe kidney was suspected, the pathology being confirmed by abdominal ultrasonography.
Giant Ulcers or Walled-off Perforations of the Duodenum
Authors: Robert Lloyd Pinck, Barry Taylor Held
Journal: New England Journal of Medicine (1961)

LARGE ulcers of the duodenum are rare. Only -L# 21 cases of duodenal ulcers of 2 cm. or more have been reported in the literature. These so-called giant duodenal ulcers may involve the entire duodenal bulb or the greatest part of it. Paradoxically, despite their size, they are often missed on barium studies of the gastrointestinal tract. Brdiczka,1 in 1931, was the first to report this lesion, and he presented 3 cases at that time. Since then, 18 additional cases have been reported. Of this total of 21, only 43 per cent were accurately diagnosed before surgery or post-mortem examination. . . .
Abstract 1800: Expression analysis of PI3K pathway genes in head and neck cancer.
Authors: Nur Buyru, Seda Ekizoglu, Emin Karaman, Ozgun Enver
Journal: Cancer Research (2013)

Abstract Head and neck cancer (HNC) is a heterogenous group of malignant tumors which includes neoplasias of the oral cavity, the pharynx, the larynx and paranasal sinuses. Squamous cell carcinomas comprise more than 95% of all head and neck cancers. The vast majority of HNC is related to exposure to carcinogens, including tobacco, alcohol, betel nut, and sexually transmitted viral pathogens such as human papilloma viruses (HPV). However, only a small fraction of tobacco and alcohol users develop the disease suggesting that genetic factors may play a key role in HNC. Increasing evidence indicate that mTOR is a central regulator of cell growth, proliferation, survival and dysregulation of the PI3K/Akt/mTOR signaling pathway that occurs in many tumors including head and neck cancer. The TSC complex (TSC1/TSC2) negatively regulates mTOR by inhibiting a small GTP binding protein, Rheb, considered to be the direct activator of mTOR. On the other hand, the Ras protein upregulates PI3K signaling which is an upstream effector of mTOR. When PI3K activates Akt, the dual function phosphatase PTEN negatively regulates it. Human cancers frequently harbor activating mutations in the p110 catalytic subunit of PI3K or genomic amplification of Akt. Activated Akt also promotes survival under conditions of cellular stress. In this study we investigated the expression of the critical genes (mTOR, K-ras, PI3KCA, TSC1, RHEB, PTEN and AKT1) acting in this pathway. For this purpose, we analyzed expression levels of these genes in 49 matched HNC tumor and non-cancerous tissue samples by quantitative RT-PCR. We observed a significant downregulation of the mTOR (p=0.005), TSC1 (p=0.001), and PTEN (p=0.000) mRNA expressions. On the other hand, a slight decrease was also observed in K-ras, Akt1 and PI3KCA mRNA levels in tumor tissues compared to the non-cancerous ones. However, the difference in the expression levels of these genes between the two groups were not statistically significant. Whereas we didn't observe any difference in Rheb mRNA expression level in tumor tissue when compared to the non-cancerous tissue samples. mTOR, TSC1, and PTEN mRNA expression levels were decreased 0.48, 0.44 and 0.32 % in HNC tumor tissue samples compared to non-cancerous tissue samples, respectively . Our result indicate that, the PI3K pathway has an important function in HNC progression with the contribution of more than one gene of this pathway. Citation Format: Nur Buyru, Seda Ekizoglu, Emin Karaman, Ozgun Enver. Expression analysis of PI3K pathway genes in head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1800. doi:10.1158/1538-7445.AM2013-1800 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
A2.05 Carbamylated autoantigens facilitate the break of tolerance: A novel mechanism in the pathogenesis of autoimmune arthritis
Authors: JS Dekkers, MK Verheul, JN Stoop, PA van Veelen, GMC Janssen, TW Huizinga, LA Trouw, RE Toes
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Rheumatoid arthritis is characterised by an immune response against posttranslational modified proteins, in particular citrullinated and homo-citrullinated (carbamylated) proteins. Posttranslational protein modification can result in the generation of neo-epitopes that may subsequently trigger auto-immune responses. Antibodies recognising carbamylated proteins (anti-CarP antibodies) are present in sera of RA-patients as well as in different animal models of arthritis. It is currently unknown how responding B cells interact with homo-citrullinated proteins or whether carbamylated self-proteins induce a breach of tolerance. We hypothesise that not only carbamylation of foreign, but also self-proteins can induce anti-carbamylated protein responses both at the T-cell and B-cell level, enabling T-cell dependent antibody production against carbamylated autoantigens. <h3>Materials and methods</h3> Mice were immunised with carbamylated antigens (ovalbumin/murine albumin/murine fibrinogen) or non-modified antigens. T cell responses were studied by proliferation assays and cytokine ELISAs. Murine anti-CarP hybridomas were sequenced using single cell PCR-based antibody cloning technology. Reactivity of human anti-CarP antibodies towards CaFCS and albumin was determined for by ELISA 160 RA-patients of the Leiden Early Arthritis Cohort and controls. <h3>Results</h3> After Ca-mAlb immunisation, mice developed high titers of anti-CarP antibodies, recognising different carbamylated foreign- and auto-antigens. In contrast, no anti-CarP antibodies were detected in mAlb immunised mice. Similar responses (i.e. anti-CarP antibody responses against carbamylated human albumin) were observed in RA-patients. Murine monoclonal anti-CarP antibodies show a similar pattern of cross-reactivity towards carbamylated antigens, together indicating that homo-citrulline is seen in a “hapten-like manner” by responding B cells. Analysis of Ig gene sequences revealed high numbers of somatic mutations, indicative of antigen-driven selection for antibody generation. T cell cultures derived from Ca-mAlb immunised mice responded to stimulation with Ca-mAlb, but not to the native protein. <h3>Conclusions</h3> Carbamylation of both foreign as self-proteins can facilitate a breach of tolerance, resulting in formation of carbamylated protein-specific T-cell and B-cell responses in mice. In mice, homo-citrulline-residues are detected by anti-CarP-antibodies in a “hapten” like manner. Interestingly, carbamylated albumin, which is able to break tolerance in mice, is also recognised by anti-CarP antibodies in RA-patients. These data provide first evidence explaining the abundance of carbamylated self-proteins recognised by anti-CarP antibodies.