tbuckley/cabot-search huggingface dataset:
Insulin Resistance and Insulin Secretory Dysfunction as Precursors of Non-Insulin-Dependent Diabetes Mellitus: Prospective Studies of Pima Indians
Authors: Stephen Lillioja, David M. Mott, Maximilian Spraul, Robert Ferraro, James E. Foley, Eric Ravussin, William C. Knowler, Peter H. Bennett, Clifton Bogardus
Journal: New England Journal of Medicine (1993)

The relative roles of obesity, insulin resistance, insulin secretory dysfunction, and excess hepatic glucose production in the development of non-insulin-dependent diabetes mellitus (NIDDM) are controversial. We conducted a prospective study to determine which of these factors predicted the development of the disease in a group of Pima Indians.
P78 Can Pet Standard Uptake Variable (suv) Predict Disease Progression In Early-stage Non-small Cell Lung Cancer (nsclc)?
Authors: F. Frost, G. Jones, J. Greenwood, M. Ledson, M. Walshaw
Journal: Thorax (2014)

<h3>Introduction</h3> The correlation between SUV on PET-CT and prognosis in NSCLC has been the subject of much debate. We were interested in whether SUV<sub>max</sub> values could be used to determine which cases of early stage (1–2) NSCLC were likely to progress. <h3>Methods</h3> We reviewed all 93 histologically proven early stage NSCLCs seen at our tertiary centre over a one year period. We defined those with SUV<sub>max</sub> in the upper quartile as the high SUV group and compared these with the remainder. Historical data were considered to allow subsequent outcomes to be established. <h3>Results</h3> Median follow up was 772 days during which time there was a 17% mortality rate [all-cause median time to death 338 days]. The median SUV<sub>max</sub> for the cohort was 10.1, and those in the upper quartile all had results over 15.0. The high SUV<sub>max</sub> group (n = 27) and low SUV<sub>max</sub> group (n = 68) had similar baseline characteristics, received similar treatment regimens and there were no significant differences in tumour size between the groups. Disease progression and mortality were both significantly higher in those with SUV<sub>max</sub> in the upper quartile, despite this group tending to have earlier disease (see Table 1). Retrospective analysis using Youdin’s index suggested that the optimal threshold for predicting disease progression was not significantly different when cases with nodal involvement were excluded [SUV<sub>max</sub> 15.0 vs 15.5] <h3>Conclusions</h3> Our results suggest that SUV<sub>max</sub> may indeed help identify those patients with early stage NSCLC at higher risk of progression. In our large cohort those with an SUV<sub>max</sub> of &gt;15 were over 3 times more likely to develop progressive disease than those with lower results and this was independent of tumour size or nodal involvement. Whether individuals in the higher-risk group would benefit from increased surveillance or adjuvant therapy remains to be established.
FRI0236 Structure and function of the fibrin network in patients with churg-strauss syndrome
Authors: P. Krawiec, B. Batko, T. Iwaniec, W. Tłustochowicz, L. Mastalerz, A. Undas
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Churg-Strauss syndrome is a rare systemic necrotizing vasculitis, characterized by severe asthma, blood eosinophilia and eosynophilic infiltration of tissue. In the course of the disease thromboembolic incidence has been reported. Depending on the study the incidence of arterial occlusion ranging between 3.1-18.7% and a prevalence of venous occlusion between 5.8-30%. <h3>Objectives</h3> We want to test the hypothesis that fibrin structure/function is unfavourably altered in patients with Churg-Strauss syndrome, which could be a novel prothrombotic mechanism tha operates in this disease. <h3>Methods</h3> Ex vivo plasma fibrin permeability, turbidimetry and efficiency of fibrinolysis were investigated in 35 patients with CCS free of history of thrombotic events (24 female, 11 male, aged 48 [range, 21-80] years. The control group comprised 35 age- and sex-matched healthy volunteers. All patients were in stable phase of the disease. <h3>Results</h3> Compared with controls, patients with CCS were characterized by significantly lower clot permeability (p&lt;0.0001) indicating pores of smaller size in the fibrin network, shorter lag phase (p&lt;0.0001) indicating quicker formation of fibrin clot, greater maximum clot absorbancy (p&lt;0.0001) indicating thicker fibrin fibres and prolonged clot lysis time (p&lt;0.0001). Fibrinogen (r=-0.55, p=0.0007), interleukin-6 (r=-0.37, p=0.0283) but not C-reactive protein (r=-0.12, p=0.5075) was inversely correlated with clot permeability and positively with clot lysis time (r 0.44 to 0.48; all p&lt;0.02). Interestingly, both IgE and eosinophilia were inversely correlated (r -0.39 to -0.48; p&lt;0.02) with clot permeability and positively associated (r 0.36 and 0.35; p&lt;0.05) with clot lysis. <h3>Conclusions</h3> This study is the first to show that Churg-Strauss syndrome is associated with unfavorably altered plasma fibrin clot phenotype, including resistance to fibrinolysis, which represents a novel prothrombotic mechanism that operates in this disease. <h3>Disclosure of Interest</h3> None Declared
SP0042 Raynaud’s Phenomenon: A Clinical Symptom that Must be Diagnosed by Capillaroscopy
Authors: A. Herrick
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Nailfold capillaroscopy plays a key role in the assesssment of the patient with Raynaud's phenomenon, in that it allows early identification of the patient with an underlying systemic sclerosis (SSc)-spectrum disorder [1,2]. This session will review the criteria for primary (idiopathic) Raynaud's phenomenon, outline the rationale for separating this out from secondary Raynaud's phenomenon (with a focus on SSc-related Raynaud's phenomenon) [3], discuss capillaroscopic abnormalities as a predictor of SSc [4,5], and discuss the recently proposed criteria for very early SSc [6,7] (highlighting capillaroscopy). Upon completion of the session, participants should be able to: Discuss the role of capillaroscopy in the assessment of the patient presenting with Raynaud's phenomenon. Describe the rationale for very early diagnosis of SSc. <h3>References</h3> Herrick, A.L. &amp; Cutolo, M. Clinical implications from capillaroscopic analysis in patients with Raynaud's phenomenon and systemic sclerosis. <i>Arthritis Rheum</i>. <b>62</b>, 2595-2604 (2010). Cutolo, M., Sulli, A. &amp; Smith, V. Assessing microvascular changes in systemic sclerosis diagnosis and management. <i>Nat. Rev. Rheumatol</i>. <b>6</b>, 578-587 (2010). Herrick, A.L. The pathogenesis, diagnosis and treatment of primary and secondary Raynaud's phenomenon. <i>Nat. Rev. Rheumatol</i>. <b>8</b>, 469-79 (2012). Koenig, M, et al. Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. <i>Arthritis Rheum</i>. <b>58</b>, 3902-3912 (2008). Ingegnoli, F. et al. Improving outcome prediction of systemic sclerosis from isolated Raynaud's phenomenon: role of autoantibodies and nail-fold capillaroscopy. <i>Rheumatol.</i><b>49</b>, 797-805 (2010). Matucci-Cerinic, M. et al. The challenge of early systemic sclerosis for the EULAR Scleroderma Trial and Research Group (EUSTAR) community. It is time to cut the Gordian knot and develop a prevention or rescue strategy. <i>Ann. Rheum. Dis.</i><b>68</b>, 1377-1380 (2009). Avouac, J. et al Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group. <i>Ann. Rheum. Dis.</i><b>70,</b> 476-481 (2011). <h3>Disclosure of Interest</h3> None Declared
Reduced 123I Ioflupane Binding in Bilateral Diabetic Chorea
Authors: Kenichiro Sato, Ayumi Hida, Masashi Kameyama, Miyako Morooka, Sousuke Takeuchi
Journal: Clinical Nuclear Medicine (2016)

We report a 64-year-old man with diabetic chorea whom we investigated with dopamine transporter SPECT, F FDG PET, Tc ethylcysteinate dimer (ECD) SPECT, and I metaiodobenzylguanidine (MIBG) scintigraphy. Dopamine transporter SPECT revealed reduced I ioflupane binding in the bilateral striatum. F FDG PET showed metabolic dysfunction in the bilateral striatum, as shown in earlier studies. Tc ECD SPECT revealed reduced brain perfusion in the bilateral caudate nucleus and putamen. I MIBG scintigraphy revealed no cardiac sympathetic nerve dysfunction. Our case suggests a possible nigrostriatal presynaptic dopaminergic involvement in diabetic chorea.
Clinical, Basic Researchers Find Common Ground in San Diego
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Clinical, Basic Researchers Find Common Ground in San Diego Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 12, 17 June 1992, Pages 922–924, https://doi.org/10.1093/jnci/84.12.922 Published: 17 June 1992
Cytokine and Chemokine Analysis in Bronchoalveolar Lavage Fluid of Acute Eosinophilic Pneumonia
Authors: Kazuyuki Nakagome, Takehito Kobayashi, Tomoyuki Soma, Makoto Nagata
Journal: Journal of Allergy and Clinical Immunology (2015)

Acute eosinophilic pneumonia (AEP) is characterized by a massive pulmonary infiltration of eosinophils. Mechanisms regulating the selective accumulation of eosinophils in AEP have not been fully established.The objective of this study was to analyze cytokine and chemokine responses to evaluate the mechanisms of eosinophil accumulation in alveolar spaces. We measured cytokine and chemokine concentrations in bronchoalveolar lavage fluid (BALF) of AEP (n = 10), sarcoidosis (n = 8), or hypersensitivity pneumonitis (n = 10) using ELISA. The concentrations of IL-5, thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and monocyte chemotactic protein (MCP)-4 were elevated in BALF of AEP. The concentrations of GM-CSF, eotaxin, regulated upon activation, normal T expressed and secreted (RANTES), MCP-2, MCP-3, IFN-γ-inducible protein of 10 kDa (IP-10), monokine induced by IFN-γ (Mig) and IFN-inducible T cell α chemoattractant (I-TAC) were slightly increased in AEP, however, they were not significant. These findings suggest that IL-5, TARC, MDC, and MCP-4 may play an important role in the accumulation of eosinophils in AEP.
Increase in Glomerular Filtration Rate in Patients with Insulin-Dependent Diabetes and Elevated Erythrocyte Sodium–Lithium Countertransport
Authors: Susan Carr, Jean-Claude Mbanya, Trevor Thomas, Pauline Keavey, Roy Taylor, K. George M.M. Alberti, Robert Wilkinson
Journal: New England Journal of Medicine (1990)

Increased sodium–lithium countertransport in erythrocytes is found in patients with insulin-dependent diabetes mellitus (IDDM) and nephropathy. To determine whether such an increase precedes the onset of nephropathy and, if so, whether it is associated with changes in renal function, we measured erythrocyte sodium–lithium countertransport in 52 patients with IDDM but not nephropathy or hypertension and in 32 control subjects.
Abstract 1627: Requirement for the Src family kinase, Fyn, in proliferation of BCR-ABL1 transduced bone marrow and aneuploidy in CML
Authors: Xiaolin Lu, Adrienne Howard, Yin Gao, Melissa Singh, Joya Chandra
Journal: Cancer Research (2010)

Abstract Oncogenic signals stemming from the BCR/ABL kinase drive the development and progression of chronic myeloid leukemia (CML). Hence, therapies blocking kinase activity have proven extremely successful at managing this hematological malignancy. However, treatment of the terminal and progressed state of CML, blast crisis, remains difficult. Previous work from our group has identified the Src family kinase, Fyn, as being upregulated in blast crisis CML. We also reported that knockdown of Fyn slowed CML growth in vitro and in vivo and sensitized cells to BCR-ABL1 kinase inhibition with imatinib. Recent work using microarray profiling of kinase inhibitor resistant cells from a separate group has shown that imatinib resistance is associated with Fyn expression. In the current study, we utilized bone marrow cells from Fyn deficient mice to test the requirement for Fyn in p210 BCR-ABL1 mediated survival. Bone marrow cells from Fyn knockout and Fyn wildtype mice were harvested and transduced with a GFP expressing retroviral construct (MigR1) or MigR1-p210 BCR-ABL1. Cells were sorted for GFP expression and BCR-ABL1 expression was confirmed by Western blotting. Cell growth in culture was monitored over the course of three weeks in Fyn deficient and wildtype cells expressing BCR-ABL1. Fourteen days post sorting, the number of cells lacking Fyn were more than 50% lower than Fyn wildtype cells transduced with BCR-ABL1. Clonogenic assays further indicated that Fyn significantly promotes BCR-ABL1 induced bone marrow cell growth. Colony numbers in Fyn deficient cells expressing BCR-ABL1 were less than half that seen in Fyn wildtype cells. To address the role for Fyn kinase activity in these effects, constitutively active and dominant negative Fyn constructs have been transduced into BCR-ABL1 expressing cells. Constitutively active Fyn caused a high degree of chromosomal aberrations, fusions and aneuploidy suggestive of genomic instability. Taken together, these data highlight a significant role for Fyn in BCR-ABL1 mediated proliferation and secondary chromosomal aberrations, which are both features characteristic of blast crisis CML. Our results indicate that strategies to inhibit Fyn expression and kinase activity will be therapeutically relevant for progressed and/or refractory CML patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1627.
Abstract 5294: The difference of serum RNA profile: RNA extraction and detection method.
Authors: Satoko Takizawa, Hideo Akiyama, Satoshi Kondo, Nobuyoshi Kosaka, Takahiro Ochiya
Journal: Cancer Research (2013)

Abstract Serum miRNA profiles are widely reported by many .research groups, but they do not always coincide well. The reason of this difference is suggested to be, at least in some cases, due to a difference in the RNA extraction or detection method. In this report, we compare the miRNA expression profiles of RNAs extracted from (1) extracellular vesicles precipitated by ultra-centrifuging (2) precipitation of ExoQuick (3) whole serum by QIAGEN miRNeasy (4) whole serum by Toray "3D-Gene" RNA extraction reagent from liquid sample kit. In addition to this, the comparison of data obtained by different detection tools will be also shown. In these days, the whole miRNA expression profiling can be done by multiple qRT-PCR, microarrays, and Next Generation Sequencing. However, the feature of each method will reflect to the obtained data and it is no surprise that data obtained by different tools do not match perfectly. We will compare the serum miRNA expression profiles detected by (1) “TaqMan” Array MicroRNA Card (2) QIAGEN miScript miRNA PCR Array (3) “3D-Gene” Human miRNA oligo chip, and discuss the base of method for serum miRNA profiling. Citation Format: Satoko Takizawa, Hideo Akiyama, Satoshi Kondo, Nobuyoshi Kosaka, Takahiro Ochiya. The difference of serum RNA profile: RNA extraction and detection method. [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 5294. doi:10.1158/1538-7445.AM2013-5294
"Overly prescriptive" targets pose threat to clinical commissioning groups
Authors: G. Iacobucci
Journal: BMJ (2013)

England’s new clinical commissioning groups could be placed at “serious financial risk” if asked to meet tough new government targets without additional funding, a representative body has warned.

NHS Clinical Commissioners warned that the Department of Health’s updated mandate to NHS England1 could lead to CCGs becoming unsustainable, because the revised plans had not been fully costed.

The warning came as one of the largest commissioning groups in England said that it was facing a deficit of £11m (€13m; $18m) this year because of a surge in activity in urgent …
PWE-151 Cell-Mediated Immune Recognition of Cea Is Associated with Early Tumour Recurrence Following Resection of Colorectal Cancer
Authors: C Brown, M Scurr, G Betts, A Gallimore, A Godkin
Journal: Gut (2013)

<h3>Introduction</h3> Colorectal cancer (CRC) is one of the commonest malignancies in men and women. Clinical staging is used to predict prognosis after resection. The interaction of the cancer with the adaptive cellular immune response plays an important role in disease pathogenesis, but this relationship may be compromised by a population of regulatory Foxp3<sup>+</sup> CD4<sup>+</sup> T cells (Tregs). Here, the 5 year post-operative clinical outcome was correlated with pre-operatively measured anti-tumour immune responses. <h3>Methods</h3> Eighty patients with non-metastatic CRC, undergoing a resection with curative intent, were recruited over 24 months. CD4+ T cell responses to tumour associated antigens (CEA and 5T4) were compared to control antigens (PPD and HA). The influence of immune regulation was measured by repeating the assays after <i>in vitro</i> depletion of Tregs. Clinical databases were interrogated for details, including morbidity and mortality data, and the five year overall survival (OS), time to progression (TTP), and progression free survival (PFS) was calculated. These parameters were compared to the original details of pre-operative anti-tumour immune responses. <h3>Results</h3> The most important clinical factor influencing patient outcome was the colorectal cancer itself, and hence there was no significant difference between five year OS (55%), TTP (62%) and PFS (52%). As expected the disease was most likely to recur in subjects with more advanced tumours (Duke’s C p = 0.04) and male sex. However, irrespective of the tumour stages Duke’s A-C, the most significant risk factor for tumour recurrence was the presence of anti-CEA CD4+ T cell responses, the majority of which were suppressed by Tregs (p = 0.002). The magnitude of these responses was greater in the group with disease recurrence (p = 0.004). Pre-operative responses to other antigens, including the tumour antigen 5T4, did not reflect outcome. <h3>Conclusion</h3> The presence of pre-operative anti-CEA immune responses identifies patients most likely to experience CRC recurrence during the 5 year follow-up period. This relationship holds true irrespective of the tumour stage. This information might be used to direct adjuvant treatment strategies. <h3>Disclosure of Interest</h3> None Declared.
AB1410 Questionnaire survey for disease-related knowledge level in 149 gout patients in south china
Authors: Z.X. Li, C.J. Zou, Q.H. Li, X. Ou-Yang, Y.Q. Mo, H.R. Schumacher, L. Dai
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> The prevalence of gout in China has been increasing to as high as 15% in some reports in the past 2 decades. Optimal management including patient education has been emphasized in clinics, but few reports on patient knowledge about gout have been published. <h3>Objectives</h3> To investigate the disease-related knowledge level of patients with gout in South China in order to identify important targets for patient education. <h3>Methods</h3> A survey of 154 patients with gout was conducted using a questionnaire in Chinese modified from Zhang et al.<sup>[1]</sup> This had 10-items concerning essential areas of knowledge of gout. Data were analyzed by multiple logistic regressions to identify factors associated with gout awareness. <h3>Results</h3> 5 patients could not finish the questionnaire because of communication problems or low education so 149 patients were recruited for statistical analysis. 133 (89.3%) patients were male and 16 (10.7%) female. The mean age was 54.9±15.8 (range 19∼94) years. The mean duration of gout was 3.8±3.2 years, and varied from 3 days to 24 years. Education levels were stratified as a) primary school or lower (20.1%), b) junior high school (2.1%), c) high school (39.6%) and d) college or above (18.1%). The mean of correct answers was 6.6±2.2, with a median of 7(5-8). The following were numbers of correct answers (%): 133 (89.3%) patients knew that too much uric acid causes gout, with 64 (43%) patients knowing that crystals inside the joint cause attacks of gout. 138 (92.6%) patients recognized acute attacks by painful swollen joints, and 105(70.5%) patients knew NSAIDs or colchicine as effective drugs for acute attacks. 90(60.4%) patients recognized that colchicine can prevent attacks induced by urate -lowering therapy (ULT). 83 (55.7%) patients knew allopurinol as a kind of urate-lowering drug. Only 72(48.3%) patients knew the optimal SUA level is ≤6mg/dl and 44 (29.5%) patients knew that urate-lowering drugs should be taken lifelong. Logistic regression showed that high education significantly predicated the awareness of gout-related knowledge. The other factors including age, sex, disease duration, annual income, the number of affected joints, frequency of acute attacks, tophus formation and frequency of doctor visits were not predicators. <h3>Conclusions</h3> Gout patients in South China were familiar with the characteristics and management of acute attacks, but had poor knowledge on ULT. Patient education for our population should be focused on the use of urate-lowering drugs, treatment duration, optimal target SUA level and prevention of attacks, especially for patients with low education. <h3>References</h3> Zhang LY, et al. Development and evaluation of a survey of gout patients concerning their knowledge about gout.J Clin Rheumatol, 2011;17: 242-248 <h3>Disclosure of Interest</h3> None Declared