tbuckley/cabot-search huggingface dataset:
FRI0313 Detection of anti-granulocyte macrophage colony-stimulating factor autoantibody in systemic lupus erythematodes
Authors: S. Ooka, H. Nakano, Y. Takakuwa, Y. Murakami, T. Kiyokawa, H. Yamada, S. Ozaki
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic lupus erythematodes(SLE) causes various symptoms in the respiratory system. Ground glass opacity (GGO) with SLE is conventionally considered interstitial pneumonia caused by the deposition of immune complexes. However, in most cases, ground glass opacity is not related to disease activity or inflammation. It is thus hypothesized that GGO is due to pulmonary alveolar proteinosis (PAP). <h3>Objectives</h3> Anti-Granulocyte Macrophage colony-stimulating Factor(GM-CSF) autoantibody is a cause of PAP. We therefore measured anti-GM-CSF autoantibody in sera of patients with SLE to test the hypothesis that PAP occurs in lupus pulmonary disease. <h3>Methods</h3> The samples were obtained from a total of 64 japanese patients in our hospital. They were diagnosed according to the 1997 criteria for SLE. The enzyme-linked immunosorbent assay was performed according to a modified version of the method described previously (1) with sera being diluted 100-fold with phosphate-buffered saline. 50μl diluted sera were transferred to a plate coated with 1μg/ml of GM-CSF (Escherichia coli derived) and the plate was kept at 4 degrees temperature for 8 h. After washing, autoantibodies captured by GM-CSF were detected by peroxidase-labeled anti-human IgG antibodies. Color was detected using o-Phenylenediamine and the absorbance was measured at 450 nm. <h3>Results</h3> Anti-GM-CSF autoantibodies were detected in 53 percent of SLE patients, with the cuttoff level being 2SD (standard deviation) of the value of the healthy serum. The titers varied, and were significantly higher in SLE patients than in patients with systemic scleroderma. Furthermore, GGO in high-resolution CT was significantly related to the anti-GM-CSF autoantibody titers (p=0.01). The patient with the highest titers had decreased respiratory function with massive ground glass opacity in both lungs. Bronchoalveolar lavage was performed, and PAP was confirmed. The presence of anti-GM-CSF autoantibodies may be a predictor of the onset of PAP because increased levels of autoantibodies were detected two years prior to onset of pulmonary disease in this patient. <h3>Conclusions</h3> This is the first report to systematically measure anti-GM-CSF autoantibodies in patients with SLE. PAP was present in pulmonary disease that was conventionally considered interstitial pneumonia in patients with SLE. It is important to measure anti-GM-CSF autoantibodies because the treatment differs for PAP and interstitial pneumonia in patients with SLE. <h3>References</h3> Kitamura, T et al. 1999. Idiopathic pulmonary alveolar proteinosis as an autoimmune disease with neutralizing antibody against granulocyte. macrophage colony stimulating factor. J. Exp. Med. 190:875.880. <b>Disclosure of Interest</b>: None Declared
Abstract 990: Efficacy of various chemotherapeutic agents on 5-FU-resistant human gastric cancer cell lines and their mechanisms.
Authors: Mamoru Nukatsuka, Takashi Kobunai, Ayako Nakamura, Kazuhiko Hayashi, Teiji Takechi
Journal: Cancer Research (2013)

Abstract Purpose: Four 5-fluorouracil (5-FU)-resistant human gastric cancer cell lines were established by the long-term exposure of parent cell lines (MKN45, MKN-74, KATO-III, and NCI-N87) to 5-FU. The cytotoxicity and mechanisms of several chemotherapeutic agents were then investigated using 5-FU-resistant gastric cancer cell lines. Method: 5-FU-resistant cell lines were established by continuous exposure to escalating concentrations (1-5 μM) of 5-FU over a 1-year period. The sensitivities of the cell lines to chemotherapeutic agents (paclitaxel, docetaxel, cisplatin, oxaliplatin, epirubicin, and SN-38) were then evaluated using the WST-8 colorimetric assay. To elucidate the mechanisms of resistance, the gene expressions and copy numbers were measured using an Agilent Technologies whole human genome oligo DNA microarray and a CGH microarray. The protein and mRNA expressions of a target enzyme of 5-FU, thymidylate synthase (TS), were also investigated using western blotting and RT-PCR, respectively. Results: The IC50 ratios of the 5-FU-resistant cell lines were 2.6 to 15.6 times higher than those of the parent cell lines in vitro. MKN-45/5-FU showed cross-resistance to cisplatin and oxaliplatin and KATO-III/5-FU showed cross-resistance to SN-38, while MKN-74/5-FU showed collateral sensitivities to docetaxel, cisplatin, and oxaliplatin, and NCI-N87/5-FU showed collateral sensitivities to cisplatin, oxaliplatin, SN-38, and epirubicin. RT-PCR showed that TS mRNA expression was higher in the parent cell lines than in the 5-FU-resistant cell lines, and the TS protein expression level was also higher in all the resistant cell lines. For MKN-45/5-FU and KATO-III/5-FU, not only the mRNA expression level but also the TS gene copy number was increased. Interestingly, the expression of MAP3K15, which is an apoptosis-facilitating factor, increased in NCI-N87/5-FU, which showed collateral sensitivity to cisplatin, oxaliplatin, SN-38, and epirubicin. Conclusion: Analyzing the molecular mechanisms of 5-FU-resistant cell lines may be useful for the development of effective chemotherapy regimens for relapsed gastric cancer after 5-FU-based chemotherapy. Citation Format: Mamoru Nukatsuka, Takashi Kobunai, Ayako Nakamura, Kazuhiko Hayashi, Teiji Takechi. Efficacy of various chemotherapeutic agents on 5-FU-resistant human gastric cancer cell lines and their mechanisms. [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 990. doi:10.1158/1538-7445.AM2013-990
PWE-088 Negative lower GI investigations: miss rates in colorectal cancer
Authors: L To, S Mills, T Townsend, K Leiper
Journal: Gut (2012)

<h3>Introduction</h3> Retrospective studies have confirmed that colonic investigations may miss a diagnosis of colorectal cancer (CRC) with a wide variation in reported miss rates.<sup>1 2</sup> Colorectal cancer miss rates of up to 12%, 22% and 50% have been reported for colonoscopy, barium enema and sigmoidoscopy, respectively. <h3>Methods</h3> A retrospective study was conducted to determine the diagnostic miss rate of colorectal cancer at our institution. All patients diagnosed with colonic or rectal adenocarcinoma between 2006 and 2010 were identified from the Royal Liverpool and Broadgreen University Hospital Trust histopathology database. Data were collected using the computerised systems and case notes. A miss was defined as a patient investigated with barium enema (BE), CT abdo-colon enhanced (CTACE), CT colonoscopy (CTC), flexible sigmoidoscopy and/or colonoscopy, and discharged without being followed-up or diagnosed with CRC in the 5 years preceding the subsequent CRC diagnosis. <h3>Results</h3> During the study period, 579 patients were diagnosed with colorectal cancer. The notes were irretrievable or had insufficient documentation in 5 cases. Twenty-two (3.8%) cases were considered misses: 5 (0.8%) were administrative misses, where patients were lost to follow-up, or they cancelled or failed to attend an appointment; in one case (0.2%), there was a clinician-associated miss, where an inappropriate choice of investigation was performed (a flexible sigmoidoscopy missed a proximal CRC); and 16 (2.8%) were technical misses, where CRC was missed with an appropriate choice of investigation. Of the technical misses, 10 (1.7%) were radiological (0.7%, 0.7% and 0.3% for BE, CTACE and CTC respectively) and 8 (1.4%) were endoscopic (0.5% and 0.9% for flexible sigmoidoscopy and colonoscopy). 45% of missed cancers were left-sided and below the splenic flexure. <h3>Conclusion</h3> This study has shown a lower miss rate in our institution than previously reported,<sup>3</sup> and when compared with other studies. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Frenette CT</b>, Strum WB. Relative rates of missed diagnosis for colonoscopy, barium enema, and flexible sigmoidoscopy in 379 patients with colorectal cancer. <i>J Gastrointest Cancer</i> 2007;<b>38</b>:148–53. 2. <b>Somasekar A</b>, James L, Stephenson BM, <i>et al.</i> The value of auditing negative lower GI investigations preceding a final diagnosis of colorectal cancer. <i>Colorectal Dis</i> 2009;<b>11</b>:740–4. 3. <b>Graham M</b>, <i>et al. Endoscopy</i> 2005;<b>37</b>:A275.
SAT0048 Synovial Lymphocytic Aggregates Predict Clinical Response to Certolizumab Pegol in Rheumatoid Arthritis (Clinical and Pathological Response to Certolizumab-Pegol (Clip-Cert) Study): Table 1
Authors: M. Di Cicco, S. Kelly, F. Humby, N. Ng, A. Nerviani, V. Rocher, R. Hands, M. Bombardieri, C. Pitzalis
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The identification of biomarkers of clinical outcome to guide therapeutic decisions in rheumatoid arthritis (RA) would bring major benefits to patients and considerable health-economic value. There is data suggesting that response to TNF alpha inhibitors (TNFi) in RA may partly be explained by modulation of synovial ectopic lymphocytic aggregates (ELN) within the synovial tissue, although this is still controversial. Certolizumab pegol is a pegylated fully humanized TNFi. Whether specific synovial pathotypes predict response to the drug is unknown. <h3>Objectives</h3> The aim of this study was to investigate whether the presence of synovial ELN at baseline predicts clinical response to treatment with certolizumab pegol in RA patients. <h3>Methods</h3> 25 biologic-naïve RA patients who qualified for TNFi therapy according to NICE guidance (National Institute for Health and Clinical Excellence, http://guidance.nice.org.uk/TA186) was recruited at Barts and the London Hospital. Patients underwent ultrasound guided synovial biopsy of an active joint prior to commencing therapy with certolizumab pegol. Following 3 months of therapy, response to treatment was assessed according to EULAR response criteria. Paraffin embedding sequentially cut sections of synovial tissue underwent H&amp;E staining and immunohistochemical staining for CD20 to detect B cells. Sections were graded as either diffuse or aggregate infiltrate as previously described [Manzo, Eur J Immunol 2005]. The study received local ethics approval. <h3>Results</h3> Characteristics of patients at baseline and clinical outcome after 3 months of therapy with comparison between ELN- and ELN+ are shown in Table 1 (Chi square or Mann Whitney test, as appropriate) Presence of ELN+ is strongly associated with a significant post- treatment lower DAS28 (0.01) and conversely significant higher Delta DAS28 (0.003) as well as good/moderate EULAR response. A stepwise logistic regression analysis was performed by entering several baseline variables: gender, age, disease duration, presence of erosions, RF and CCP status, use of steroids, DAS28, HAQ, presence of ELN. Only presence of ELN was identified as a potential predictor of EULAR response (Fisher exact test p&lt;0.001; Logistic Regression OR=11.0, 95% CI=1.10-109.67, p=0.041). <h3>Conclusions</h3> Our findings strenghts the relevance of synovial pathotype in relationship with clinical outcome. In particular, the presence of ELN may be a potential predictor of primary clinical response to certolizumab pegol treatment, in line with previous data observed for other TNFi. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5564
Regression of Focal Nodular Hyperplasia of the Liver After Oral Contraceptive Discontinuation
Authors: CHRISTIAN CÔTÉ
Journal: Clinical Nuclear Medicine (1997)

There is uncertainty regarding the role, if any, of oral contraceptive steroids in the development of focal nodular hyperplasia of the liver. A case of focal nodular hyperplasia of the liver diagnosed by scintigraphy in a 33-year-old woman is presented. The lesion regressed in a dramatic way after oral contraceptive discontinuation. This case report suggests that oral contraceptives may influence the natural history of focal nodular hyperplasia of the liver, and that a trophic effect on the liver lesion is quite possible.
Identification of robust and disease-specific stromal alterations in spondyloarthritis synovitis
Authors: Nataliya Yeremenko, Troy Noordenbos, Gemma Rigter, Juan Cañete, Paul-Peter Tak, Dominique Baeten
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> The cellular and molecular pathways driving synovial inflammation and stromal remodeling in spondyloarthritis (SpA) remain largely unknown. As SpA and rheumatoid arthritis (RA) show clearly distinct patterns of structural remodeling, the authors conducted this study to identify cellular and molecular pathways specific for SpA synovitis by an unbiased microarray screening approach of the inflamed synovial tissue in both conditions. <h3>Materials and methods</h3> Synovial tissue samples were obtained by arthroscopy from individuals with SpA, RA and gout. RNA was extracted and gene expression profiling was performed. Top differentially expressed genes were validated on three independent cohorts of SpA versus control samples by qPCR and immunohistochemistry. qPCR was also performed on paired SpA synovial biopsies before and after tumour necrosis factor (TNF) blockade. Synovial fibroblasts and tissue biopsies were used for ex vivo cultures. <h3>Results</h3> The microarray experiments identified a signature set of 359 genes that discriminated with high certainty between SpA and RA patients. Both, technical validation by qPCR on the same samples, and biological validation in an independent cohort of early, untreated SpA and RA yielded a strong correlation between the microarray and qPCR data. The gene signature was also consistent as pathway analysis revealed that top-ranking upregulated transcripts in SpA were related to myocyte/myofibroblast biology. Several of these genes, including alpha smooth muscle actin (αSMA), showed up to 100-fold upregulation in SpA versus RA. Analysis of gout versus SpA samples confirmed that these genes were specifically upregulated in SpA synovitis rather than downregulated in RA. Paired analysis of SpA samples before and after TNF blockade showed that the expression of these genes was not altered. Immunohistochemistry for αSMA identified increased expression in SpA versus RA in the intimal lining and synovial sublining layers. Double immunofluorescence and FACS analyses revealed a colocalisation of αSMA and fibroblasts marker CD90. Preliminary data suggest that regulation of transdifferentiation of synovial fibroblasts towards myofibroblasts is induced by platelet-derived growth factor and transforming growth factor β, as αSMA expression is elevated upon stimulation of synovial fibroblasts with these mitogenic factors. Finally, targeting myofibroblasts with a specific inhibitor of the PDGF receptor tyrosine kinase imatinib mesylate in ex vivo tissue cultures led to a significant decrease in the production of pro-inflammatory cytokines. <h3>Conclusions</h3> This study identified a robust and disease-specific increase in myofibroblasts in SpA synovitis. The reason for this increase and the potential role of these cells in inflammation and, more importantly, structural remodeling in SpA are currently under investigation.
Potential Role of Gut Microbial Metabolites in Allergy Prevention in Children
Authors: Caroline Roduit, Remo Frei, Ruth Ferstl, Susanne Loeliger, Charlotte Braun-Fahrländer, Erika Von Mutius, Juha Pekkanen, Jean-Charles Dalphin, Josef Riedler, Roger Lauener, Liam O'Mahony
Journal: Journal of Allergy and Clinical Immunology (2016)
PMO-156 Plasma HBsAG levels correlate with liver cccDNA in tolerant children with infancy acquired chronic hepatitis B infection
Authors: I Carey, Y Zen, M J Bruce, M Horner, S Bansal, D Vergani, G Mieli-Vergani
Journal: Gut (2012)

<h3>Introduction</h3> Plasma HBsAg reflects the transcriptional activity of covalently closed circular (ccc) DNA within the liver rather than the absolute amount of cccDNA copies. Higher plasma HBsAg levels are reported among tolerant than immuno-active HBeAg positive chronic hepatitis B (CH-B) patients. Only limited information is available on the interaction of plasma HBsAg, expression of HBsAg and HBcAg within the liver and liver relaxed circular (RC) HBV DNA and cccDNA in patients with infancy-acquired CH-B. <h3>Aims</h3> To evaluate whether there is a relationship between plasma HBsAg and HBV DNA levels and HBsAg/HBcAg expression within the liver and liver RC HBV DNA and cccDNA in tolerant children with infancy-acquired CH-B. <h3>Patients</h3> 23 children (eight males, median age 10.2 yrs) with infancy-acquired CH-B (all HBeAg+) in tolerant stage underwent liver biopsy prior to antiviral therapy with lamivudine and interferon-α. <h3>Methods</h3> Plasma HBsAg and HBV DNA levels were measured at therapy baseline by Abbott ARCHITECT® assay and real-time TaqMan PCR [both log<sub>10</sub> IU/ml]. Baseline liver RC HBV DNA and cccDNA was quantified by real-time TaqMan PCR [copies/ng genomic DNA]. Immunostaining of formalin-fixed, paraffin-embedded liver specimens assessed HBsAg and HBcAg expression [# of positive cells per 1000 hepatocytes]. Results are presented as median, range. <h3>Results</h3> Baseline plasma HBsAg levels were 4.67 (3.7–5.1), HBV DNA was 8.2 (7.1–8.9) both log<sub>10</sub> IU/ml and ratio HBsAg/HBV DNA 0.57 (0.44–0.65). Liver RC HBV DNA was 4.41 (2–5.3) log<sub>10</sub> copies/ng genomic DNA and cccDNA was 363 (0.3–3632) copies/ng genomic DNA. HBsAg is predominantly expressed in cytoplasm focally associated with membranous staining, 2.9 (0–56.9) positive cells/1000 hepatocytes, in contrast to HBcAg expressing predominantly in the nucleus, 8.3 (0.5–83.6) positive cells/1000 hepatocytes. There were positive bivariate Spearman correlations between plasma HBsAg levels and liver cccDNA (r=0.41, p=0.05), HBcAg liver expression and cccDNA (r=0.44, p=0.05), liver RC HBV DNA and cccDNA (r=0.67, p=0.04) and a trend towards correlation between plasma HBsAg and HBsAg liver expression (r=0.38, p=0.07). <h3>Conclusion</h3> Plasma HBsAg levels correlate with liver cccDNA in tolerant children with infancy-acquired chronic hepatitis B infection suggesting that plasma HBsAg levels acts as a surrogate marker of cccDNA within the liver in tolerant patients. <h3>Competing interests</h3> I Carey grant/research support from: BMS, Gilead, Y Zen: None declared, M Bruce: None declared, M Horner: None declared, S Bansal: None declared, D Vergani: None declared, G Mieli-Vergani: None declared.
Usefulness of direct peroral cholangioscopy in the management of intrahepatic lithiasis
Authors: Paulo Massinha, Nuno Nunes, Rodrigo Liberal, Filipa Ávila, Vera Santos, Ana Rego, José Pereira, Nuno Paz, Maria Duarte
Journal: Endoscopy (2014)

Intrahepatic lithiasis is a rare condition in Western countries, and the majority of reported cases to date have been associated with extrahepatic biliary tract gallstones and hereditary cystic disorders, such as Caroli disease. The usual clinical presentation consists of repeated episodes of cholangitis, which can be complicated by liver abscess and sepsis. The management of intrahepatic gallstones is challenging. Surgical therapy has been the most effective approach; however, few cases have shown the effectiveness of management with percutaneous cholangioscopy [1] [2]. The role of direct peroral cholangioscopy in the treatment of intrahepatic gallstones has not yet been assessed [3].
Liddle's Syndrome Revisited -- A Disorder of Sodium Reabsorption in the Distal Tubule
Authors: Mauricio Botero-Velez, John J. Curtis, David G. Warnock
Journal: New England Journal of Medicine (1994)

In 1963 Liddle et al.1 described a disorder that simulated primary aldosteronism, characterized by severe hypertension and hypokalemia but with negligible secretion of aldosterone. They theorized that this was “a disorder in which the renal tubules transport ions with such abnormal facility that the end result simulates that of a mineralocorticoid excess.” We describe a woman with this syndrome (the index case1) in whom renal failure eventually developed and who received a cadaveric renal transplant at our institution in 1989. Her disorder resolved after transplantation, with normalization of the aldosterone and renin responses to salt restriction. The woman's extended . . .
Role of EUS in Pre-operative Localization of Insulinomas
Authors: S Singh, S Puli, J Talapaneni, M Oropeza-vail, M Olyaee
Journal: Endoscopy (2006)

Introduction: Insulinoma is an uncommon pancreatic neuro-endocrine tumour characterized by hyperinsulinemic hypoglycemia. It is important to surgically remove this tumor as it can cause potentially lethal hypoglycemia. The conventional imaging techniques have limitations in accurate pre-operative localization of small duodeno-pancreatic neuroendocrine tumors. The high spatial resolution of endoscopic ultrasound (EUS) permits better detection of such small tumors. We describe a report of 12 patients supporting the above observation. Results: 12 patients with insulinoma who had surgery at our institution were reviewed. (7 enucleation, 3 distal pancreatectomy, 2 unresectable). One of the patient with unresectable tumor was locally invasive and other had vascular invasion not detected on EUS prior to surgery. 9 of the tumors were located in the tail, 2 in head of pancreas and 2 in the body of pancreas (one patient had two tumors). The mean size of tumors was 2.72×2.18cm. Three patients had surgical resection done before EUS was available at our center. Pre-operative CT scan failed to localize the tumor in these patients. EUS done in the other nine patients accurately localized the tumor prior to surgical resection. Immunological staining on fine needle aspiration obtained at the time of EUS was consistent with insulinoma and revealed malignancy in one patient. One patient had two tumors which were detected on EUS prior to surgery. Conclusion: Our experience with 12 patients is in accordance with previous reports claiming EUS to be the method of choice for preoperative imaging and localization of pancreatic islet cell tumors. Preoperative evaluation is necessary for planning pancreatic surgery to assess for resectability
COMPLICATIONS FROM ULTRASOUND GUIDED FEMORAL ARTERIAL ACCESS IN PEDIATRIC CARDIAC CATHETERIZATION: A PROSPECTIVE SINGLE CENTER COHORT STUDY
Authors: John Alexander, Benjamin Waller, Thomas Yohannan, Agrawal Vijaykumar, Hannah Lloyd, Marsha Stewert-Sellers, Shyam Sathanandam
Journal: Journal of the American College of Cardiology (2015)
Survey of Oncologists about Shortages of Cancer Drugs
Authors: Keerthi Gogineni, Katherine L Shuman, Ezekiel J Emanuel
Journal: New England Journal of Medicine (2013)

In this survey of oncologists, most reported that they were unable to prescribe a preferred cancer drug at least once over the previous 6 months because of a drug shortage. Some oncologists had to delay treatment or make substitutions, often with more expensive drugs.