tbuckley/cabot-search huggingface dataset:
A3.01 Serum and synovial fluid concentration of RF subclasses in characterisation of the inflammatory reaction in rheumatoid arthritis
Authors: Zl Kolarov, I Altankova, M Baleva, S Monov, R Shumnalieva
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Although the immunological hallmark of rheumatoid arthritis (RA) –&nbsp;rheumatoid factor (RF), has modest disease specificity the determination of its subclasses could&nbsp;show individual characteristics of the pathogenic process with possible correlation with the clinical phenotype and treatment respond. <h3>Objectives</h3> To analyse the serum (S) and synovial fluid (SF) concentration of RF subclassesin RA patients (pts) and to compare them and clinical data and structural damages in regard to their use as markers for the disease activity (DA), progression and possible treatment decisions. <h3>Methods</h3> 151 RA pts according to the 1987 ACR criteria were included in the study. Levels of RF IgG, IgM and IgA in S and SF samples were measuredby ELISA and analysed in regard to the laboratory data for DA, radiological and functional stage. <h3>Results</h3> There was a correlation between the S and SF concentration of RF IgG (r = 0.778, p &lt; 0.001), RF IgA (r = 0.631, p &lt; 0.001) and RF IgM (r = 0.577, p &lt; 0.001). Double positivity for RF subclasses was found as follows: RF IgM<sup>+</sup>/IgA<sup>+</sup> in 62% of the pts, RF IgM<sup>+</sup>/IgG<sup>+</sup> in 25% of the pts, RF IgG<sup>+</sup>/IgA<sup>+</sup> in 17% of the pts, and the simultaneously presence of the three subclasses RF IgM<sup>+</sup>/IgA<sup>+</sup>/IgG<sup>+</sup> in 11% of the pts. S and SF concentrations of RF IgG were lower in pts with diseases duration more than 10 years and lower functional status, the opposite was found for RF IgA concentrations. There was no correlation between the systemic and local concentration of RF IgA with the DA. The latter was found to correlate with higher S concentration of both RF IgA<sup>+</sup>/IgM<sup>+</sup>. <h3>Conclusions</h3> RF&nbsp;accounts for the inflammatory process in RA. Systemic and local concentrations of RF subclasses characterise the pathogenic process where RF IgG is involved in the early and IgA in the latter stages of the autoimmune inflammatory reaction. RF subclass determination in the clinical practice could be used for pts follow-ups and in the process of making treatment decisions with personalising the disease modifying therapy.
Abstract 1627: Proteome-wide analysis of echinoderm microtubule associated protein like 4 – anaplastic lymphoma kinase (EML4-ALK) network in lung cancer
Authors: Guolin Zhang, Ann Chen, Lanxi Song, Jianing Fu, Fumi Kinose, Yun Bai, Bin Fang, Jiannong Li, Steven Eschrich, John Koomen, Eric Haura
Journal: Cancer Research (2011)

Abstract The translocation of echinoderm microtubule associated protein like 4 – anaplastic lymphoma kinase (EML4-ALK) defines a unique, new subset of patients with non small cell lung cancer (NSCLC). It represents a novel diagnostic biomarker and therapeutic target for NSCLC. PF 02341066 is a ALK small tyrosine kinase inhibitor that has demonstrated high clinical activity in EML4-ALK- positive NSCLC patients. We sought to characterize the signaling network used by EML4-ALK and reveal potential new therapeutic targets. We used tandem affinity purification (TAP) and liquid chromatography-mass spectrometry (LC-MS/MS) to map protein-protein interactions and anti-phosphotyrosine immunoprecipitation coupled with LC-MS/MS to map tyrosine phosphorylation. We selected the human NSCLC H3122 cell line for our studies as it is sensitive to PF 02341066 and harbors ELM4-ALK. Quantitative western blotting results show that activities of MET, ALK, AKT, ERK and STAT3 were inhibited by treatment with PF 02341066. Proteome-wide analysis of tyrosine phosphorylation of the ALK signaling pathway were examined. In total, 311 tyrosine phosphorylated proteins (487 unique phosphorylated sites) were identified. Of those, 73 pTyr sites (62proteins) were upregulated and 78 pTyr sites (58 proteins) were downregulated by 1uM PF02341066. Using TAP, we identified 13 proteints interacting with EML4-ALK including GRB2 and SHC1. Core interactions were verified by coupling of immunoprecipitation to Western blot and mass spectrometry. A comprehensive physical ALK network was generated by integrating both phosphoproteomic data and interactional partners using pathway analysis algorithms. Two adaptors, SHC1and GAB2, are suggested as the first outlets of signaling propagation from ALK. Other sublevels directly connected with ALK may allow further understanding the mechanism of ‘ALK addiction’. A sub-network composed of 35 cell death associated proteins was created. An ongoing functional analysis including siRNA and small inhibitor screen on this small network should validate druggable targets. This network approach has potential translational applications to identify novel approaches to treatment of ALK addicted lung cancers and could be useful in patients with acquired resistance to ALK inhibitors. 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 1627. doi:10.1158/1538-7445.AM2011-1627
Does advanced endoscopic imaging increase the efficacy of surveillance colonoscopy?
Authors: E. Dekker, J. East
Journal: Endoscopy (2010)

Colonoscopy with adenoma resection is thought to reduce the incidence of colorectal cancer (CRC) by up to 80 % [1], and recent randomized population-based data confirm that flexible sigmoidoscopy can reduce left-sided CRC development and death from CRC [2]. However, recent reports demonstrate that some patients under colonoscopic surveillance still develop CRC, particularly in the right colon [3] [4]. This may be explained by a rapid progression of adenomas, by incomplete removal of adenomas, or by the fact that colonoscopy is not infallible for the detection of adenomas. Indeed, a systematic review of back-to-back colonoscopies demonstrated that 15 %–32 % of adenomas were overlooked [5]. On top of this, subtle flat or depressed lesions are more difficult to detect and may have been missed by both colonoscopies in study designs of this type.
Absorption of Chloramphenicol Sodium Succinate after Intramuscular Administration in Children
Authors: Frank Shann, Victor Linnemann, Angela Mackenzie, Jane Barker, Michael Gratten, Nicholas Crinis
Journal: New England Journal of Medicine (1985)

Because it is thought that chloramphenicol is poorly absorbed after intramuscular administration, we compared blood levels of chloramphenicol after intramuscular administration with those after intravenous administration in children with a variety of diagnoses. Fifty-seven children were studied on 62 occasions while they were receiving chloramphenicol sodium succinate (25 mg of chloramphenicol per kilogram of body weight) intramuscularly every six hours. The peak level of chloramphenicol was 19.5 +/- 5.99 micrograms per milliliter (mean +/- S.D.) in 11 children after the first dose and 31.4 +/- 12.99 micrograms per milliliter in 51 children after two or more doses. The lowest peak level after intramuscular administration was 13 micrograms per milliliter, which is in the therapeutic range of 10 to 30 micrograms per milliliter. Thirteen children were studied on 17 occasions while they were receiving chloramphenicol sodium succinate (25 mg of chloramphenicol per kilogram) intravenously every six hours. The peak level of chloramphenicol was 19.4 +/- 6.37 micrograms per milliliter in eight children after the first dose and 28.2 +/- 11.09 micrograms per milliliter in nine children after two or more doses. The area under the serum level curve was not significantly different after intramuscular and intravenous administration. We conclude that chloramphenicol sodium succinate is well absorbed after intramuscular administration. This route is cheaper, it demands less staff time, and it does not carry the risks of sepsis and overhydration associated with intravenous therapy.
PMO-021 Optimising out-patient parenteral iron administration using total dose infusions: Abstract PMO-021 Table 1
Authors: J Swabe, C Wijayasekara, J Allen, F Cummings
Journal: Gut (2012)

<h3>Introduction</h3> Iron deficiency is common in the inflammatory bowel disease population (36%–90%<sup>1</sup>) and is often poorly managed. Guidelines on the management of iron deficiency anaemia recommend that parenteral iron should be used if oral iron supplementation is either ineffective or not tolerated.<sup>1</sup> Iron Sucrose (IS, Venofer<sup>®</sup>) infusions take on average 85 min to be administered and require between 5 and 13 infusions for a therapeutic dose of iron to be given. Ferric Carboxymaltose (FC, Ferinject<sup>®</sup>) is a total dose infusion parenteral iron preparation. It requires 1–2 infusions for therapeutic dose delivery and allows shorter administration times. We audited the outcomes of switching from IS to FC in terms of therapeutic efficacy and patient experience. <h3>Methods</h3> Current practice with IS was prospectively audited over a 6-week period. All admissions for parenteral iron to the Managed Care Unit (MCU) were included. Nursing staff completed a questionnaire including patient demographics, indication and record the patient journey. Patients completed a satisfaction survey. FC was introduced in early December 2011 and data collected for a further 6-week period. FC was dosed according to the summary of product characteristics, updated 25 October 2011. <h3>Results</h3> Data are presented as median (range) unless otherwise stated. All patients in the FC group and 45% in the IS group were cannulated at the first attempt. No patients in the FC group and 20% in the IS group reported severe pain on cannulation. All patients in the FC group and 83% in the IS group received their full course. It took a median -days (range) of 49 (30–113) for the IS patients and 9 (8–10) for the FC patients to complete their treatment course. Two patients in the FC group who had previously had IS commented on the advantage of fewer infusions. In both groups over 70% of patients rated their experience as good or very good. <h3>Conclusion</h3> This real life data shows clear advantages of using a TDI parenteral iron preparation. A reduction in the number of admissions and time spent in the MCU is demonstrated with more patients receiving the recommended dose in a shorter time. Efficiency can be improved by advanced prescribing and our data may show gaps in the knowledge of prescribers. Patient satisfaction remained high with FC. <h3>Competing interests</h3> J Swabe: None Declared, C Wijayasekara: None declared, J Allen: None declared, F Cummings speaker bureau with: Vifor Pharmaceuticals. <h3>Reference</h3> 1. <b>Gomollón F</b>, Gisbert JP. Anemia and inflammatory bowel diseases. <i>World J Gastroenterol</i>. 2009;<b>15</b>:4659–65.
Abstract 553: High prevalence of human papilloma virus in esophageal squamous cell carcinoma: A preliminary study
Authors: Kim Vaiphei, Rakesh Kochhar, Gladson David Masih, Usha Dutta
Journal: Cancer Research (2012)

Abstract Background:Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers with poor prognosis. ESCC has been associated with Human Papilloma Virus (HPV) genotypes 16 and 18. Incidence of HPV infection ranges from 0 to 67% in different parts of the world. Aim: to analyze prevalence of HPV infection in ESCC tumor and adjoining mucosa by HPV genotyping test. Material and method: Fresh tissue samples were obtained from ESCC tumor (group I) and adjoining mucosa (group II). Biopsies were subjected to frozen section for histological characterization. Aliquots of DNA extract was used for the linear array genotyping test. Results: There were 56 patients with paired samples, M:F=9:5. HPV was positive in 42/56 (75%), mean age of positive samples ranged from 41 to 63 years, the mean value in group I was 56.63±6.96 and in group II was 54.31±7.13 years (p&amp;gt;0.05). Majority had more than one genotype. The common genotypes observed were HPV 52, 55, 31, 65 and 16 in carcinoma and adjoin mucosa as well. Smoking showed a significant association with HPV positivity. p63 and p16 oncoproteins correlated with degree of tumor differentiation, not with the viral subtypes or positive status. HPV 6 and 11 were also positive in certain number of cases. Conclusion: we documented high prevalence of high risk HPV infections in tumor and adjoining mucosa in ESCC, supporting the concept of persistent infection by oncogenic HPV in cancer development. HPV 52 was the commonest genotype. It highlights importance of documenting the prevalent viral genotype in a defined geographic area in cancer prevention and treatment. Key words: Human Papilloma Virus genotype; Human Papilloma Virus genotype 52; esophageal squamous cell carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 553. doi:1538-7445.AM2012-553
AB0969 Accuracy of blind intra-articular injections in patients with osteoarthritis of the knee. An ultrasonography controlled study
Authors: G. Filippou, V. Di Sabatino, A. Adinolfi, G. Brizi, I. Bertoldi, M. Galeazzi, B. Frediani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Viscosupplementation by intra-articular injections (IAI) of hyaluronic acid in the knee is widely used for symptom relief in patients with osteoarthritis of this joint. Previous studies have demonstrated that blind IAI are not always accurate in placing the needle in the knee joint space. <h3>Objectives</h3> The aim of our study was to establish by ultrasonography the rate of correct, intra-articular delivery of the drug in patients with knee joint osteoarthritis, undergoing IAI of hyaluronic acid, and to individuate the main factors that could influence the IAI outcome <h3>Methods</h3> All patients with knee osteoarthritis referred to our outpatient clinic for IAI were enrolled in the study. Demographic data of patients, Body Mass Index (BMI) and radiological grade of osteoarthritis were recorded. Injections were performed by two medical doctors, one with many years experience in IAI and the other with only a few months experience, in a random way (alternating one patient to each during the sessions). The access used for IAI was decided by the operator at the time of injection. A small air bubble was intentionally left in the syringe so that ultrasound could precisely identify the drug. Within 15 min of injection, patients were examined by ultrasound to define drug position (intra- or extra-articular). SPSS software was used for statistical analysis. <h3>Results</h3> 42 patients (42 knees) were enrolled in the study (38 females). Air bubbles were easily recognized in all patients and exact drug position was readily identified. 24 IAI were performed by the expert operator. In 12 cases, lateral midpatellar access was used, while in the other cases anterolateral access was preferred. The drug was correctly positioned in 28 cases (67%). Logistic regression analysis demonstrated that the only variable influencing IAI outcome (among age, BMI, grade of osteoarthritis, operator experience, presence of intra-articular effusion) was operator experience. <h3>Conclusions</h3> Two out of three IAI were correctly placed in the knee joint. Operator experience was the most important factor for correct intra-articular injection. BMI, effusion and the grade of osteoarthritis did not seem to influence the outcome of IAI. Correct training in IAI is therefore very important. <h3>References</h3> Jackson DW, Evans NA, Thomas BM. Accuracy of needle placement into the intra-articular space of the knee. J Bone Joint Surg Am. 2002 Sep;84-A(9):1522-7 Qvistgaard E, Kristoffersen H, Terslev L, Danneskiold-Samsøe B, Torp-Pedersen S, Bliddal H. Guidance by ultrasound of intra-articular injections in the knee and hip joints. Osteoarthritis Cartilage. 2001 Aug;9(6):512-7. <h3>Disclosure of Interest</h3> None Declared
Psychotherapeutic Control of Hypertension
Authors: Richard A. Stone, James De Leo
Journal: New England Journal of Medicine (1976)

We conducted a six-month trial to determine the effect of psychologic relaxation on blood pressure. Alterations of peripheral sympathetic-nervous-system activity, as reflected by changes of dopamine-beta-hydroxylase in plasma, were evaluated, and plasma volume and plasma renin activity were measured. Treated patients exhibited significant (P < 0.05) reductions of blood pressure when supine and upright, and of plasma dopamine-beta-hydroxylase activity, and furosemide-stimulated renin activity when upright. Blood-pressure changes after six months correlated best with differences in plasma activity of dopamine-beta-hydroxylase with patients supine (r = 0.54; P < 0.05) and upright (r = 0.62; P <0.05). These results suggest that a reduction of peripheral adrenergic activity contributes importantly to the improvement of hypertension observed with this form of therapy. Furthermore, the decrease of furosemide-stimulated plasma renin activity suggests that alterations of the renin-angiotensin system may help lower blood pressure in certain patients. (N Engl J Med 294:80–84,1976)
Mitochondrial donation is "not unsafe," review confirms
Authors: J. Wise
Journal: BMJ (2014)

A third scientific review by the UK Human Fertilisation and Embryology Authority has confirmed that no evidence exists indicating that two mitochondrial donation techniques are unsafe.1 Scientists and medical charities are now urging the UK government to act swiftly to change the law during the current parliament.

The regulator’s scientific panel reiterated the conclusion of its two earlier reviews, carried out in 2011 and 2013, that there was no evidence that the two techniques, maternal spindle transfer and pronuclear transfer, are unsafe. These two methods allow the transmission of both parents’ nuclear DNA but involve replacing abnormal mitochondria with normal mitochondria from a donor oocyte.

The panel concluded that the techniques were potentially useful for people wishing to have their own genetically related child but whose offspring were at risk of severe or lethal genetic disease because of mutations in the mitochondrial DNA carried by the mother.

Mutations in the mitochondrial DNA can cause a range of rare but serious diseases that can be fatal. …
Soybeans Show Promise in Cancer Prevention
Authors: J. Ziegler
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Soybeans Show Promise in Cancer Prevention Get access Jan Ziegler Jan Ziegler Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 22, 16 November 1994, Pages 1666–1667, https://doi.org/10.1093/jnci/86.22.1666 Published: 16 November 1994
Abstract 4253: In vivo activity of small molecule HIF2α inhibitors
Authors: Ana Marguerita Metelo, Li Xiang, Rania Baker, Alexa Burger, Randall Peterson, Othon Iliopoulos
Journal: Cancer Research (2012)

Abstract Hypoxia-inducible factor (HIF) is a central regulator of the cellular response to hypoxia. Hypoxia promotes HIF activity by increasing its stability, transcriptional activity and translation. HIF target genes involved in several cellular processes including proliferation, angiogenesis, metabolism and promotion of the “stem-cell” phenotype. In normoxic conditions, HIF-α is recognized for degradation by the von Hippel-Lindau tumor suppressor protein (VHL). Loss-of-VHL function leads to constitutive expression of HIF regulatory subunits and consequent over-expression of HIF-target genes. We and others have shown that HIF2a is necessary and sufficient for the development of VHL-related renal cell carcinoma. We have developed small molecules that repress HIF-2α translation, in vitro, by enhancing the binding of Iron-Regulatory Protein 1 (IRP1) to the Iron-Responsive Element (IRE) within the 5′-UTR of HIF-2α mRNA (Zimmer M. et al. Molecular Cell 2008;32: 828-848). We showed that these small molecules down-regulate HIF2a expression in vitro, in all renal cell carcinoma cell lines. To validate these small molecules in vivo, we tested their efficacy on wild-type zebrafish embryos. Treatment of 3 days post fertilization zebrafish embryos with 100microM of the hypoxic mimetic DMOG or hypoxia dramatically upregulated the expression of HIF-target genes, such as Vascular Endothelial Growth Factor (Vegf), erythropoietin (Epo) and prolyl-hydroxylase 3 (Phd3). Pre-treatment of embryos with the small molecule HIF2a inhibitor 76 potently decreased the DMOG-induced upregulation of HIF target genes. The IC50 values of these small molecules were significantly less in vivo than in vitro. We are currently testing the efficacy of HIF2a inhibitors in rescuing the VHL zebrafish phenotype and prolonging survival of VHL mutant zebrafish embryos. In addition, data on the efficacy of these inhibitors on the growth of human renal cell carcinoma cells as tumors in the nude mouse xenograft assay will be presented. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4253. doi:1538-7445.AM2012-4253
253 COMPARISON OF SURVIVAL OUTCOMES BETWEEN PATIENTS WITH VIRAL AND NON-VIRAL RELATED HEPATOCELLULAR CARCINOMA: A LARGE MULTI-CENTRE STUDY
Authors: B. Christensen, S. Bell, P. Gow, M. Fink, M. Bailey, A. Majumdar, W. Kemp, S. Roberts
Journal: Journal of Hepatology (2013)