tbuckley/cabot-search huggingface dataset:
S123 The Role of Nasal Potential Difference Testing in Difficult Cases of Possible Cystic Fibrosis
Authors: N Simmonds, R Pabary, I Ya-Tung, D Bilton, EWFW Alton, JC Davies
Journal: Thorax (2012)

The European CF Diagnostic Working Group guidelines include nasal potential difference (nPD) testing when conventional tests (sweat chloride/<i>CFTR</i> mutation analysis) are inconclusive. This specialist measure of epithelial ion transport is available in relatively few centres throughout the UK and Europe and therefore may not be readily considered as a diagnostic option. We have been offering a clinical service for several years, for both our own patients and those referred in. Here, we report the results of a retrospective audit over a 2.5 year period with an aim to increase awareness and understanding of the test. Between March 2009 and Sept 2011, 66 patients (58% female) underwent testing. Median (range) age was 18 (2–67) years. Children under the age of 8 were most commonly tested whilst under anaesthetic for a bronchoscopy. 59% of patients were referred from other centres. The majority of sweat chloride results (52%) were in the 30–60 mEq borderline range. 95% had undergone first-line CFTR mutation analysis: 62% had none, 37% had one and 1 subject had 2 mutations, one of which was considered a ‘sequence variant’. One child was unable to tolerate the procedure; 6% of traces were uninterpretable due to presumed nasal inflammation. Overall, the nPD results in the context of other features led to a diagnosis of variant/atypical CF in 18%; abnormality in chloride secretion was more sensitive than sodium absorption. We were able to rule out CF ‘to the best of current diagnostic ability’ in 60% including 6 of 8 patients diagnosed with CF in early childhood, but now considered so unlikely to have the disease that re-investigation was warranted. In a further 13% of cases, nPD was of good quality but was difficult to categorise; in addition to the full CFTR gene sequencing performed routinely, we will investigate these patients for mutations in genes such as ENaC. Nasal PD was well tolerated and helpful in clarifying the diagnosis in the majority (78%) of patients referred. It should be considered in patients for whom, despite careful work up, a diagnosis of CF is difficult to confirm or rule out.
SAT0029 Mesenchymal stem cells modulate in vitro fibroblast activity in systemic sclerosis
Authors: N. Quirici, L. Corti, C. Scavullo, W. Maglione, D.P. Comina, C. Ferri, G. Lambertenghi Deliliers, N. Del Papa
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Bone marrow (BM)-derived mesenchymal stem cells (MSC) are currently under investigation for their potential role in the management of some autoimmune diseases. Besides their regenerative effects and ability to induce tissue repair, MSC seem to possess potent immunomodulatory and anti-inflammatory effects, either by direct cell-cell interaction or by secreting different molecules able to exert a paracrine effects on local environment. <h3>Objectives</h3> Aim of the study was to evaluate the paracrine effects of BM-MSCs mesenchymal stem cells (MSC) isolated from normal individuals and patients with systemic sclerosis (SSc), on proliferation and cytokine production of cutaneous fibroblasts. <h3>Methods</h3> Fibroblasts obtained from skin punch biopsies (10 dcSSc patients and 5 healthy donors -HD) were cultured <i>in vitro</i>. MSC were isolated by plastic adherence from SSc and HD bone marrow (BM). Co-cultures were assessed with HD or SSc fibroblasts with HD or SSc MSC. Fibroblast proliferation was assessed by WST-1 assay and data were expressed as median percentage of 3 replicates. Levels of TGF-β, Stem Cell Factor (SCF), and metalloproteinase MMP-9 were detected in the co-culture supernatants by commercial ELISA Kits. <h3>Results</h3> Co-culture assays confirmed our previous results: an inhibition of SSc fibroblast proliferation, higher when fibroblasts were cultured with nBM MSCs (% of fibroblast proliferation <i>vs</i> fibroblasts without MSCs (100%): 75.8±9.9% with SSc MSCs <i>vs</i> 64.7±8.3% with nBM MSCs; <i>P</i>=0.038). In the presence of fibroblasts from healthy subjects, MSCs from normal and SSc BM equally inhibited proliferation. In comparison with basal values, the levels of the cytokines showed only in the presence of SSc fibroblasts and HD MSC a significant reduction in the content of SCF (mean±SD: 14.68±3.4 pg/ml <i>vs</i> 11.48±4.4; <i>P</i>=0.01) and TGF-β (3169.8±810 pg/ml <i>vs</i> 2450±900; <i>P</i>=0.0098), while no significant changes were observed in the presence of SSc MSC. As regards MMP-9, the basal value (mean±SD: 0.008±0.01 ng/ml) significantly increased in the presence of both HD (0.035±0.02; <i>P</i>=0.003) and SSc (0.094±0.072 ng/ml; <i>P</i>=0.01) MSC. <h3>Conclusions</h3> Our findings demonstrate that normal MSC (more than SSc-MSC) may provide an important signal for skin fibroblasts, and particularly for SSc fibroblasts, by both exerting anti-proliferative effects and down-regulating their activation state. The present results may reinforce the perspective for a future use of BM-MSC as a therapeutic option in SSc, namely for their anti-fibrotic potential. <h3>Disclosure of Interest</h3> None Declared
VITAMIN D3 LEVELS MODULATE CXCR4+ CIRCULATING PROGENITOR CELL COUNTS
Authors: Salim Hayek, Yi-An Ko, Ibhar Al Mheid, Kareem Hosny, Hina Ahmed, Brandon Gray, Keyur Patel, Iraj Hesaroieh, Greg Martin, Jinhee Kim, Edmund Waller, Arshed Quyyumi
Journal: Journal of the American College of Cardiology (2016)
Abstract 1980: Dihydroartemisinin inhibits ovarian cancer growth and metastasis via targeting PDGFRα
Authors: Xiaoguang Li, Yanling Liu, Qingxi Yue, Jianbing Zhang, Nuoxi Gong, Peizhan Chen, Hong Liu, Meiyu Geng, Fulin Qiang, Ruiwen Zhang, Hui Wang
Journal: Cancer Research (2012)

Abstract Artemisinin and its analogs, the well-established clinically used anti-malarial traditional medicine, have been proven to have potent anticancer activities. We have demonstrated that Artemisinin and analogs have significant anti-ovarian cancer effect used alone or in combination with conventional chemotherapeutic agents. However, the mechanisms of action for their anticancer activities are not completely understood. Herein we report that dihydroartemisinin, one of the most active derivatives of artemisinin, directly targets platelet-derived growth factor receptor-alpha (PDGFRα) to repress ovarian cancer growth and metastasis. Dihydroartemisinin directly interacts with PDGFRα and induces dephosphorylated inactivation and ubiquitin-mediated degradation of PDGFRα, which further inactivates downstream phosphoinositide 3-kinase (PI3K) and Mitogen-Activated Protein Kinase (MAPK) pathway and subsequently represses epithelial-mesenchymal transition (EMT) in terms of upregulation of epithelial marker E-cadherin and downregulation of mesenchymal markers N-cadherin and vimentin and transcriptional repressors Snail, Twist and Slug, leading to suppression of cell growth and metastasis in PDGFRα-positive ovarian cancer cells in vitro and in vivo mouse orthotopic ovarian cancer model. These findings may contribute to the development of more effective artemisinin-based targeted compounds as novel target therapy for the treatment of human cancers. 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 1980. doi:1538-7445.AM2012-1980
Mechanical Symptoms and Arthroscopic Partial Meniscectomy in Patients With Degenerative Meniscus Tear
Authors: Raine Sihvonen, Martin Englund, Aleksandra Turkiewicz, Teppo L.N. Järvinen
Journal: Annals of Internal Medicine (2016)

Recent evidence shows that arthroscopic partial meniscectomy (APM) offers no benefit over conservative treatment of patients with a degenerative meniscus tear. However, patients who report mechanical symptoms (sensations of knee catching or locking) may benefit from APM. To assess whether APM improves mechanical symptoms better than sham surgery. Randomized, patient- and outcome assessor-blinded, sham surgery-controlled, multicenter trial. (ClinicalTrials.gov: NCT00549172). 5 orthopedic clinics in Finland. Adults (aged 35 to 65 years) with a degenerative medial meniscus tear and no knee osteoarthritis. APM or sham surgery. Patients' self-report of mechanical symptoms before surgery and at 2, 6, and 12 months after surgery. 70 patients were randomly assigned to APM, and 76 were assigned to sham surgery. Thirty-two patients (46%) in the APM group and 37 (49%) in the sham surgery group reported catching or locking before surgery; the corresponding numbers at any follow-up were 34 (49%) and 33 (43%), with a risk difference of 0.03 (95% CI, -0.06 to 0.12). In the subgroup of 69 patients with preoperative catching or locking, the risk difference was 0.07 (CI, -0.08 to 0.22). Analyses were post hoc, and the results are only generalizable to knee catching and occasional locking because few patients reported other types of mechanical symptoms. Resection of a torn meniscus has no added benefit over sham surgery to relieve knee catching or occasional locking. These findings question whether mechanical symptoms are caused by a degenerative meniscus tear and prompt caution in using patients' self-report of these symptoms as an indication for APM. Academy of Finland.
Research in psychiatry: a co-citation analysis
Authors: J W Crawford, S Crawford
Journal: American Journal of Psychiatry (1980)

Co-citation analysis provides a methodology for investigating the structure of scientific specialties. The authors did such an analysis for psychiatry by using some 2 million references from the Social Sciences Citation Index to identify 155 clusters of publication that represent psychiatry-related areas. They report on the distribution of publications among research areas, the rate of growth in research activity, and interrelationships among disciplines.
PREDICTIVE VALUE OF EARLY AND LATE DEFINITION OF CONTRAST-INDUCED ACUTE KIDNEY INJURY AFTER CORONARY ANGIOGRAPHY OR PERCUTANEOUS CORONARY INTERVENTION
Authors: Yong Liu, Jianbin Zhao, Dengxuan Wu, Hualong Li, Shiqun Chen, Chongyang Duan, Ning Tan, Jiyan Chen
Journal: Journal of the American College of Cardiology (2016)
FRI0210 Mortality in patients with rheumatoid arthritis-associated interstitial lung disease treated with an anti-tumor necrosis factor agent
Authors: Y. J. Kim, B. S. Koo, M.-W. So, W. J. Seo, Y.-G. Kim, C.-K. Lee, B. Yoo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is commonly found in elderly patients with RA. There have been several case reports regarding the adverse effect of anti-TNF therapy in RA-ILD patients. However, to date there have been relatively few studies including large number of patients. <h3>Objectives</h3> The purpose of our study was to identify the mortality rate and the causes of death in RA-ILD patients treated with anti-tumor necrosis factor (anti-TNF). <h3>Methods</h3> We retrospectively reviewed the medical records of RA-ILD patients in a tertiary care medical center between 1995 and 2011. First, we searched for RA-ILD patients who were treated with anti-TNF agent and analyzed their clinical characteristics and the causes of death. Survival rate according to age at the initiation of anti-TNF therapy was also analyzed. To determine the effect of anti-TNF therapy on mortality, the patients were divided into two groups, i.e. the DMARDs (disease modifying antirheumatic drug) group patients who were only treated with DMARDs and the anti-TNF group patients who were treated with anti-TNF agent at any point in time. We compared the clinical characteristics and survival rate between the two groups. <h3>Results</h3> Twenty four RA-ILD patients treated with anti-TNF agent were analyzed. All six deaths occurred within 14 months after treatment initiation, and the causes of their deaths included acute exacerbation of ILD, pneumonia, septic shock, and diffuse alveolar hemorrhage. Survival rate of the patients who started anti-TNF therapy at under 70 years of age was higher than that of patients 70 years of age or older. In a total 100 RA-ILD patients of our study cohort, the DMARDs group and the anti-TNF group were composed of 76 and 24 patients, respectively. There were 13 and 6 deaths, respectively, in the DMARDs group and the anti-TNF group (17% vs. 25%). The all-cause mortality was 25 deaths/1,000 person years in the DMARDs group compared with 28 deaths/1,000 person years in the anti-TNF group. The survival rate was not significantly different between the two groups (<i>p</i> = 0.935). <h3>Conclusions</h3> Although the mortality rate of the patients who underwent anti-TNF therapy was not different from that of patients treated only with DMARDs, anti-TNF agent should be used with caution in older RA-ILD patients. <b>Disclosure of Interest</b>: None Declared
CORONARY ARTERY BYPASS AND PERCUTANEOUS INTERVENTION AFTER KAWASAKI DISEASE: THE CANADIAN PEDIATRIC EXPERIENCE
Authors: Audrey Dionne, Mohamed Bakloul, Cedric Manlhiot, Brian McCrindle, Martin Hosking, Christine Houde, Dion Pepelassis, Nagib Dahdah
Journal: Journal of the American College of Cardiology (2016)
EP-05 * POSTERIOR FOSSA EPENDYMOMA SUBGROUPS HAVE DISTINCT THERAPEUTIC AND PROGNOSTIC IMPLICATIONS
Authors: V. Ramaswamy, S. Mack, M. Taylor
Journal: Neuro-Oncology (2015)

BACKGROUND: Recent integrated genomic studies has shown that posterior fossa ependymoma comprise two distinct molecular subgroups, termed EPN-PFA and EPN-PFB, whereby EPN-PFA are typically younger and have a worse prognosis. Current standard of care for all posterior fossa ependymoma include surgery and conformal external beam radiation to the tumour bed, irrespective of extent of resection or subgroup. We sought to delineate the prognostic implications of external beam irradiation in a subgroup specific manner. METHODS: We assembled a cohort of 365 posterior fossa ependymoma's and were subgrouped using genome wide methylation arrays. Clinical details were ascertained through a retrospective chart review. RESULTS: In a primarily pediatric cohort, 10% of cases were EPN-PFB. Five-year progression free survival in EPN-PFA cases was 0.216 +/− 0.03 and EPN-PFB cases was 0.667 +/− 0.082. Five-year overall survival in EPN-PFB cases was 1 suggesting that EPN-PFB cases benefit significantly from salvage therapies. Extent of resection was a significant predictor of poor outcome in EPN-PFA cases (p = 0.012) but not EPN-PFB (p = 0.224). Upfront external beam irradiation conferred a significant survival advantage in EPN-PFA cases, however in EPN-PFB, salvage strategies could be successfully employed in patients not receiving upfront external beam irradiation. Metastatic recurrences were enriched in the EPN-PFA group (p = 0.04). CONCLUSIONS: There are significant clinical and therapeutic differences between the two principle posterior fossa ependymoma subgroups. Extent of resection remains prognostic in EPN-PFA, although gross totally resected EPN-PFA continue to have a poor outcome compared to EPN-PFB. Careful de-escalation of therapy could be considered for older children and adolescents with EPN-PFB tumours.
Increased Sodium-Lithium Countertransport Activity in Red Cells of Patients with Insulin-Dependent Diabetes and Nephropathy
Authors: Ruggero Mangili, Jeremy J. Bending, Graham Scott, Lai K. Li, Amit Gupta, GianCarlo Viberti
Journal: New England Journal of Medicine (1988)

Susceptibility to diabetic nephropathy may be related to a predisposition to arterial hypertension. We have studied the activity of sodium–lithium countertransport in red cells, a marker of risk for essential hypertension, in white European adults with insulin-dependent diabetes and diabetic nephropathy, a matched group of patients with diabetes without renal disease, and nondiabetic patients with renal disease. Measures of metabolic control and concentrations of plasma free insulin and growth hormone were similar in the two diabetic groups. The degree of impairment in renal function was similar in the diabetic and nondiabetic patients with renal disease. Body-mass index and plasma potassium concentrations were similar in all three groups. Diastolic blood pressure was elevated to a similar degree in the two groups with renal disease, as compared with that in the diabetic patients without renal disease. The rates of sodium–lithium countertransport in red cells were significantly higher in the diabetic patients with renal disease (mean ±SD, 0.55±0.19 mmol of lithium per liter of red cells per hour) than in the diabetic patients without renal disease (0.33±0.16; P<0.005) and in the nondiabetic patients with renal disease (0.31±0.14; P<0.001). Predisposition to hypertension, as indicated by elevated sodium–lithium countertransport activity in red cells, may serve as a marker for the risk of renal disease in patients with insulin-dependent diabetes. (N Engl J Med 1988; 318: 146–50.)
A7.13 IRAK1 Rs3027898 Polymorphism: A Variant Implicated in the Pathogenesis of more than one Inflammatory Disease
Authors: A Chatzikyriakidou, PV Voulgari, AA Drosos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> IRAK1 plays significant role in TLR dependent activation of the transcription factor NF-kB, which subsequently increases the expression of many genes such as TNF-α and IL-8 related to immunological reactions. Polymorphism Rs3027898 located in the 3′-untranslated region of IRAK1 gene was studied for its association with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) predisposition. <h3>Materials and Methods</h3> The polymerase chain reaction-single strand conformation polymorphism analysis coupled with sequencing was used as the screening method for variant genotyping in 136 RA, 29 PsA, and 49 AS patients and 147 controls. <h3>Results</h3> IRAK1 polymorphism Rs3027898 was revealed to be associated with all the studied inflammatory conditions. Specifically, strong statistically significant difference was observed in polymorphism distribution between RA patients and controls (p = 0.044), PsA patients and controls (p &lt; 0.001), and AS patients and controls (p &lt; 0.001). Grouping genotypes AA and AC versus CC the statistical difference was also significant in all groups: RA versus controls (p = 0.017), PsA versus controls (p &lt; 0.001), and AS versus controls (p = 0.010). <h3>Conclusions</h3> Here, we report IRAK1 gene polymorphism association with RA, PsA, and AS. This variant, previously, was also related to RA in patients with Chinese origin, with atherothrombotic cerebral infarction in Japanese patients, while we also revealed its association with ischemic stroke. In addition, another IRAK1 gene polymorphism (Rs1059703) was also related to atherothrombotic cerebral infraction, high CRP, chronic kidney disease, the induction of vaccine-induced immunity and sepsis outcomes but this variant did not differ significantly between our studied groups and controls (data not given). Taking into account that IRAK1 gene affects the activation of transcription factor NF-kB, which is implicated in many immune related genes' expression, we could understand IRAK1 extensive association with many inflammatory conditions beyond patients' origin.
A new model for drug development using a multi-stakeholder consortium
Authors: A. K. Hall
Journal: BMJ (2014)

Cohen and Raftery highlight the difficulties of new collaborative drug development models.1 Several charities now fund and collaborate in drug research and development. This can create ethical tension if donations from the public are used for commercial gain.

In 2012, I helped create a charity called Findacure (www.findacure.org.uk), which aims to teach patient groups how to drive the drug …
PTU-244 A close shave in the management of rectovaginal endometriosis
Authors: N Bullen, M Browning, J Frappell, M Coleman
Journal: Gut (2015)

<h3>Introduction</h3> Endometriosis affects the bowel in 3–37% of all cases.<sup>1</sup>There is ongoing debate regarding the necessity of either segmental resection or full-thickness disc rectal excision. This study aimed to review the use of the laparoscopic rectal shave technique with respect to outcomes and patient satisfaction. <h3>Method</h3> Data was collected retrospectively for all patients requiring operative management of rectovaginal endometriosis between 2009 and 2014. Both electronic records and case notes were reviewed and data was collected on pre-operative symptoms, surgical procedure, length of stay, complication and re-admission rates and post-operative symptom recurrence. In addition patients answered a telephone satisfaction questionnaire. <h3>Results</h3> 52 patients underwent surgery during the study period with 69.2% carried out by a combined colorectal and gynaecological surgical team. Average age was 33.9 (21–43). Out of 52 patients 90% underwent rectal wall shave, 8% had segmental resection and 2% hysterectomy in combination with rectal shave. Surgery was performed laparoscopically in 96% with a 0% conversion rate. Average length of stay was 1.5 days with a re-admission rate of 5.8%. Major complications occurred in 2% with no patients requiring re-operation within the early postoperative period. Overall 17.3% went on to have further surgery for their endometriosis although only 3.8% required bowel resection. Patient satisfaction levels were high with a high proportion of patients having symptom improvement post surgery. <h3>Conclusion</h3> The laparoscopic rectal shave is a successful technique for the management of rectovaginal endometriosis with low complication rates and high patient satisfaction. Outcomes are improved by using combined colorectal and gynaecological surgical teams. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Revised American Society for Reproductive Medicine classificationof endometriosis: 1996. Fertil Steril. 1997;67:817–821