tbuckley/cabot-search huggingface dataset:
P05 * VARIABILITY IN FOLLOW UP IMAGING GUIDELINES AFTER THE COMPLETION OF PRIMARY THERAPY IN GLIOBLASTOMA MULTIFORME
Authors: A. Hamdan, P. Kane
Journal: Neuro-Oncology (2014)

INTRODUCTION: There is no clear definitive follow up surveillance imaging guideline after the completion of primary therapy in glioblastoma multiforme (GBM). Here we provide the first report analysing international, national and local guidelines in GBM imaging surveillance. METHOD: We performed a systematic review of GBM management guidelines indexed in PUBMED and EMBASE databases up until October 2013. We also searched for GBM guidelines on websites of relevant international and national societies. To clarify local recommendations within the UK, we reviewed all guideline documents produced by local neuro-oncology multidisciplinary teams (MDTs; n = 28) in the UK accessed via the Care Quality Improvement Network (CQuIN) database. For all the relevant guidelines identified, we extracted imaging recommendations for the period following completion of primary therapy. RESULTS: Out of the identified guidelines produced by international and national societies, only 6 had follow up imaging guidelines with variability in imaging frequency ranging from 1-2 monthly (1 guideline), 2-4 monthly (1), 2-3 monthly (2), to 3-4 monthly (2). Twenty out of the 28 neuro-oncology MDTs had imaging guidelines. Of these, 18 had guidelines on imaging after completion of primary therapy, with also a wide variability in imaging frequency from 2 monthly (2 guidelines), 2-4 monthly (1), 3 monthly (6), 3-4 monthly (1), 3-6 monthly (2), 6 monthly (4), and yearly (2). CONCLUSION: The guidelines for follow up imaging surveillance after the completion of primary therapy in GBM are variable. Future studies should assess effectiveness of these guidelines in detecting assymptomatic GBM recurrence.
NIR-fluorescence imaging points at a role for matrix-metalloproteinases in causing irreversible cartilage damage during collagen-induced arthritis
Authors: Eline A Vermeij, Marije I Koenders, Onno J Arntz, Miranda B Bennink, Peter L E M van Lent, Wim B van den Berg, Fons A J van de Loo
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> During joint inflammation and destruction, a variety of proteases are upregulated, including different cathepsins and matrix-metalloproteinases (MMP). Enzyme activity and osteoblast activation can be quantitated in vivo by using activatable and targeting near-infrared probes. This also provides us with a tool to non-invasively monitor treatment efficacy on enzyme activity and bone remodelling. The authors investigated the role of MMPs in chondrocyte death and subsequent irreversible cartilage damage, using biophotonic imaging. <h3>Methods</h3> Collagen-induced arthritis was induced in male DBA1/J mice by immunisation with bovine collagen-type II. Mice received either anti-IL-1 sera (200 l intravenously) or normal rabbit serum as a control at day 21. Ten days later, Sense 680 probes (PerkinElmer, Waltham, MA, USA) were injected intravenously and 6 h later mice were imaged using the IVIS Lumina (Caliper Life Sciences, Hopkinton, MA, USA). The ProSense 680 probe becomes activated upon enzymatic cleavage by cathepsins. The MMPSense 680 can be activated by different MMPs. OsteoSense 680 is a fluorescent biphosphonate that binds to hydroxyapetite, a biomarker for osteoblast activation. After imaging the ankle and knee joints were dissected and processed for histology or x-ray. Ankle joints were x-ray photographed and scored for bone destruction. Subsequently, serial sections were made and stained with H&amp;E to study inflammatory cell influx, chondrocyte death, bone loss and cartilage destruction and with Safranin-O to study proteoglycan depletion. Sections were also stained for VDIPEN, a neoepitope of aggrecan cleaved by MMPs. <h3>Results</h3> All the probes showed an increased fluorescent signal intensity during arthritis. Both the ProSense and MMPSense signal was reduced three times by the anti-IL-1 treatment, whereas the OsteoSense signal was reduced 1.5 times. On the other hand, OsteoSense signal was two times higher in mice showing mild bone loss, compared to no bone loss as measured by x-ray, suggesting an increased osteoblast activity to counterbalance bone loss. Correlations were found between MMP activity and chondrocyte death (r=0.77, p&lt;0.0001), proteoglycan depletion (r=0.65, p=0.0002) and VDIPEN staining (r=0.81, p&lt;0.0001), while less correlation was found between cathepsin activity and chondrocyte death (0.39, p=0.0064). <h3>Conclusion</h3> Imaging of these three probes is a sensitive method to measure joint inflammation, connective tissue destruction and repair, and overall is fluorescence imaging a valuable tool to monitor a treatment response. These findings also suggest that irreversible cartilage damage caused by chondrocyte death is a result of enhanced MMP activity rather than cathepsin activity.
Hypertyraminemia in Cirrhotic Patients
Authors: Bahjat A. Faraj, Paul A. Bowen, James W. Isaacs, Daniel Rudman, Vernon M. Camp
Journal: New England Journal of Medicine (1976)

To evaluate the role of tyramine in hepatic disorders, we used a radioimmunoassay to study plasma concentration of tyramine in eight healthy subjects, 20 hospitalized patients without liver disease, and 13 cirrhotic patients of whom seven had hepatic encephalopathy. The effect of increasing dietary protein on tyramine level of cirrhotic patients was also assessed. No significant difference in plasma tyramine concentration was seen between normal subjects, 1.3 +/- 0.1 ng per milliliter (average +/- S.E.), hospitalized patients without hepatic disease (1.4 +/- 0.1 ng per milliliter) and cirrhotic patients without encephalopathy (2.7 +/- 0.5 ng per milliliter). However, the tyramine level in cirrhotic patients with encephalopathy, 6.4 +/- 0.1 ng per milliliter, was significantly (P less than 0.001) higher than in normal subjects or in cirrhotic patients without encephalopathy. Increasing dietary protein from 40 to 80 g per day raised fasting tyramine concentration by 30 to 70 per cent within three days in both encephalopathic and non-encephalopathic cirrhotic patients. Concentration of plasma tyramine in cirrhotic subjects was significantly correlated with that of plasma tyrosine (P less than 0.001).
Changes in the Treatment Landscape for Chronic Lymphoid Leukemia
Authors: Robin Foà
Journal: New England Journal of Medicine (2014)

After decades during which the treatment of patients with chronic lymphoid leukemia (CLL) was based on chemotherapy and more recently on chemoimmunotherapy, we are witnessing a new mechanism-driven era with the development of compounds capable of targeting the B-cell receptor signaling pathway. In this issue of the Journal, after an earlier phase 2 study,1 Byrd et al.2 present the results of the first randomized trial comparing the effect of ibrutinib, an inhibitor of Bruton's tyrosine kinase, with that of the anti-CD20 antibody ofatumumab, both used alone, for patients with relapsed or refractory CLL or small lymphocytic lymphoma. The results indicate . . .
Book: Health Impact Assessment
Authors: Anna García-Altés
Journal: BMJ (2005)

Those of us working in the healthcare sector sometimes tend to forget the big picture. When thinking about what influences health we usually think of health related services and individual choices and lifestyles. Although these are important, other issues have more influence on the health of individuals and communities, such as education, employment and working conditions, sanitation, housing, and income.​income.




Figure 1



Eds John Kemm, Jayne Parry, Stephen Palmer

Oxford University Press, £34.50, pp 450 ISBN 0 19 852629 6

Rating: ★★★




Health impact assessment is an emerging tool in the field of public health, the principal aim of which is to help planners and policy makers. It is used to assess the health consequences for a population of a policy, project, or programme that does not necessarily have health as its primary objective. It is a combination of procedures, methods, and tools by which to judge the potential effects of a policy, project, or programme on a population's health and how those effects will be distributed in the population. It provides a practical and evidence based way to consider the influence of those other determinants of health and to help in making decisions. The general objectives are to improve knowledge about the potential effects on health, to inform decision makers and affected people, and to help adjust proposed policies to mitigate the negative health effects and enhance the positive effects. As such health impact assessment can contribute to transparency in policies, as well as to reduction of health inequities.

The authors make an excellent effort to present the topic. They cover a wide range of topics: from methodological issues (both quantitative and qualitative) to practical considerations whenever undertaking an assessment (from planning to decision making), as well as some thoughts about the state of the art of health impact assessment in the international arena (presenting the most relevant experiences) and some actual examples in quite different applications (such as waste disposal, crime prevention, and agricultural policies).

Especially interesting is the use of the tool to assess the effects of a proposal on health equity in a given population—one of the fields where the tool is more extensively used. Also interesting are community involvement in the assessment process and even community development as a result of participation in an assessment process.

For me the three main points of interest in health impact assessment are that it takes into account the effects on health of policies not directly related to health; the mix of professionals (from epidemiologists to economists and engineers) and techniques involved in the assessments; and that it is a process that is based on decision making. The topics and examples in this book reflect these points well. However, the book could have benefited by giving a selection of good websites from the plethora of sites addressing health impact assessment.
Abstract 4956: Regulation of anoikis by DBC1 (Deleted-In-Breast Cancer 1) through NF-kB
Authors: Sun Park, Philip A. Riley, Benjamin Cieply, Steven M. Frisch
Journal: Cancer Research (2012)

Abstract Cancer cells that undergo epithelial-to-mesenchymal transition (EMT) evade anoikis, apoptosis induced by detachment from extracellular matrix. The mechanism of anoikis-resistance is an area of ongoing research. The gene Deleted in Breast Cancer 1, DBC1, is found in chromosomal region 8p21, which is deleted in some breast cancers, while several other cancers show DBC1 overexpression. DBC1 interacts with various proteins, such as SIRT1, ERα, RARα and SUV39H1 in a cancer context dependent manner. We found that depletion of DBC1 sensitized MCF10-A mammary epithelial cells to anoikis both in two-dimensional and three dimensional culture models. This effect was also observed in several breast cancer cell lines. Microarray analysis showed that DBC1 regulates the level of the c-FLIP in MCF10a cells, which was confirmed by RT-PCR. In addition, real time PCR studies showed that DBC1 induces other NF-kB transcription factor target genes such as Bcl2 and XIAP, some of which are known suppressors of anoikis. Luciferase assays demonstrated that DBC1 induces NF-kB transcriptional activity. NF-KB is a transcription factor that regulates genes involved in inflammatory response, cell survival and death. We found, through the use of the NF-kB inhibitors BAY 117082 and curcumin, that NF-kB suppressed anoikis. Conversely, SIRT1 –a deacetylase that inhibits NF-kB and that is itself inhibited by DBC1– promoted anoikis. The pathway in which DBC1 regulates anoikis through NF-κB will be further investigated in the future, with a view toward understanding the role of DBC1 in modulating the inflammatory signaling pathways that control anoikis. 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 4956. doi:1538-7445.AM2012-4956
PMO-117 Perturbation of the mitochondrial network architecture in an in vitro model of alcohol-induced liver toxicity
Authors: E Palma, D Clemens, R Williams, S Chokshi
Journal: Gut (2012)

<h3>Introduction</h3> Mitochondria are central to many cellular processes and are dynamic organelles that exist as a network in the form of elongated filaments and respond to the demands of the cell through cycles of fusion (binding of mitochondria) and fission (mitochondrial-fragmentation) which are driven primarily through multiple mitochondrial shaping proteins. Mitochondrial function is intimately associated with their morphology and while mitochondrial dysfunction has been previously correlated with alcohol consumption, there is a paucity of understanding regarding the impact of alcohol on the dynamic balance between fusion/fission and on mitochondrial morphology. The aim of this study was to investigate the impact of alcohol-induced liver damage on mitochondrial morphology, dynamics and to identify the precise mechanisms driving these changes. <h3>Methods</h3> Ethanol metabolising-human hepatoma cell lines VL-17A (positive for alcohol-dehydrogenase and CYP2E1) were cultured in the presence of increasing doses of ethanol (EtOH), reflecting real-life alcohol consumption. Cells were cultured with EtOH at 10 mM (safe levels), 50 mM, 250 mM (high levels) and 500 mM (highly toxic levels). Cultures were incubated in presence/absence of EtOH for 24, 48, 72 and 96 h. Post-treatment the levels of mitochondrial shaping proteins including Mitofusin-1 (Mfn-1), Mitofusin-2 (Mfn-2) and Dynamin-related protein-1 (Drp-1) were analysed by detecting protein and mRNA levels. Dynamic changes in the morphology of mitochondria were assessed by confocal microscopy. <h3>Results</h3> In the absence of alcohol, we observed no changes in the mitochondrial shaping proteins and no changes in the mitochondrial network over time. At 24 h, cells treated with 50 mM ethanol induced profound modifications in the mitochondrial network with a spot-like presentation which correlated with increased levels of Drp-1. At higher toxic levels of 500 mM, the cells display features of mitochondrial toxicity characterised by fragmentation reflecting the high level of cell death observed with this concentration. This toxicity was associated with reduced expression of Mfn-1 and Mfn-2. <h3>Conclusion</h3> For the first time we show that alcohol can profoundly perturb the equilibrium between fusion and fission which directly affects the mitochondrial morphology. This study reveals a novel finding in the pathogenesis of alcohol-induced liver toxicity. <h3>Competing interests</h3> None declared.
EUS is necessary for differential diagnosis in patients with Suspicious Gallbladder Wall Lesions
Authors: SH Lee, SM Woo, JW Yoo, JK Park, JK Ryu, YT Kim, YB Yoon
Journal: Endoscopy (2006)

Introduction: Differential diagnosis is often difficult for suspicious gallbladder (GB) wall lesions. The purpose of this study was to evaluate the efficacy of endoscopic ultrasonography (EUS) in the differential diagnosis of suspicious GB wall lesions. Methods: Preoperative EUS evaluation with transabdominal ultrasonography and abdominal computed tomography was done in 22 patients who underwent cholecystectomy because neoplastic GB wall lesions could not be ruled out between March 2005 and February 2006 in Seoul National University Hospital. We retrospectively reviewed the medical records. Results: Age of 22 patients was mean 56.5±14.7 years. Among them, 13 were male. The pathologic evaluation revealed cholesterol polyp in 3 patients, adenomyomatosis in 1 patient, adenoma in 2 patients, adenocarcinoma in 7 patients and chronic inflammatory change in 9 patients. Preoperative diagnosis for the GB wall lesions was correct only in 6 of 22 patients (27.2%) without EUS evaluation. However, preoperative evaluation supplemented by EUS more correctly diagnosed the gallbladder wall lesions (59.1%, 13/22) (p<0.05). Furthermore, preoperative evaluation with EUS for differentiation of neoplastic lesions from others was more correct (72.7%, 5/12) than without EUS (45.4%, 10/22) (p<0.01). And, preoperative EUS evaluation correctly diagnosed the GB wall lesions in 5 (71.4%) of 7 patients with gallstones and in 8 (53.3%) of 15 patients without gallstones, however, statistical differences was not significant (p=0.65). In addition, gallstones did not influenced on differentiation neoplastic lesions from others with EUS (p=0.82). Conclusions: EUS was effective in differential diagnosis of suspicious GB wall lesions regardless of the presence of gallstones. So, EUS could be recommended when neoplastic lesions could not be ruled out in patients with suspicious GB wall lesions.
The Role of Lymphoscintigraphy in Diagnosis and Monitor the Response of Physiotherapeutic Technique in Congenital Lymphedema
Authors: Lung Chang, Mei-Fang Cheng, Hsiu-Hao Chang, Yu Hsuan Kao, Yen-Wen Wu
Journal: Clinical Nuclear Medicine (2011)

We describe the case of a 4-month-old girl who was admitted for bilateral legs swelling for several weeks. Lymphoscintigraphy revealed the absence of the radiotracer proximal to the ilioinguinal nodes up to 6 hours postinjection. In light of the clinical and image findings, a diagnosis of congenital lymphedema was compatible. Systemic corticosteroid was given, and physical massage was applied at the lower extremities for 3 weeks. Repeat lymphoscintigraphy revealed faster lymphatic flow and liver visualization, demonstrating improvement in lymphatic function. This case illustrates the usefulness of lymphoscintigraphy in diagnosis and evaluating therapy response of lymphedema in children.
Abstract LB-152: Characterization of the first mouse model of anaplastic thyroid carcinoma
Authors: Mariavittoria Dima, Antonio Di Cristofano
Journal: Cancer Research (2010)

Abstract Although anaplastic thyroid carcinoma is a rather uncommon malignancy, it accounts for the vast majority of deaths from thyroid cancer. Despite considerable efforts, its dismal prognosis has not changed in decades. Building on the increasing knowledge of the molecular events involved in anaplastic carcinoma pathogenesis, we have generated a mouse model in which the Pten and p53 tumor suppressor genes have been selectively deleted in the thyroid follicular cells. By six months of age, double mutant mice develop undifferentiated, aggressive thyroid carcinomas arising, like in most human patients, from pre-existing follicular carcinomas. These tumors are invariably locally invasive, and often metastasize to the lungs. Similar to their human counterpart, they display loss of expression of most thyroid differentiation and functional markers, including Thyroid peroxidase (Tpo), Thyroglobulin (Tg), and the therapeutically relevant Sodium-iodide symporter (Nis). A combined approach, using both double mutant mice and several stable cell lines derived from tumors that developed in these mutants, is uncovering the molecular pathways involved in the transformation and dedifferentiation process, as well as pointing to novel potential targets for therapeutic intervention. In conclusion, this compound mouse mutant represents a unique, clinically relevant model of thyroid anaplastic carcinoma, and an invaluable tool for both basic and preclinical studies. 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 LB-152.
THU0533 Pain Intensity and Threshold in Rheumatoid Arthritis, Psoriatic Arthritis and Ankylosing Spondylitis Patients: Correlations with the Hamilton Depression Rating Scale
Authors: G. Bagnato, M. Atteritano, S. Sorbara, I. De Andres, R. Talotta, G. Corallo, E. Verduci, G. Miceli, D. Sangari, E. Visalli, N. Marino, S. Morgante, W. N. Roberts, G. Bagnato
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Individuals suffering from chronic pain are frequently affected by depression, which in turn increases the risk of development of chronic pain complaints over time. <h3>Objectives</h3> This study aims to investigate the relationship between depression and pain intensity and threshold in a cohort of rheumatic patients compared to healthy subjects. <h3>Methods</h3> 124 individuals of whom 50 affected by rheumatoid arthritis (RA), 23 by psoriatic arthritis (PsA), 23 by ankylosing spondylitis (AS) and 28 age-matched controls without chronic pain underwent quantitative sensory testing (QST) to assess pressure pain threshold with an algometer. Pain intensity was evaluated through the Visual Analogue Scale (VAS) and depression through the Hamilton Depression rating Scale (HAMD). <h3>Results</h3> A significant reverse correlation between HAMD values and algometer scores was found in the entire cohort of patients (p&lt;0.0001), in controls (p=0.002) and also in RA (p=0.002), PsA (p&lt;0.0002) and AS (p=0.02) patients when analyzed separately, while no significant correlation was found between HAMD and VAS values or algometer scores and VAS. We found lower pain thresholds in RA and PsA patients while no difference has been evidenced in AS patients compared to healthy controls. HAMD scores were also significantly higher in rheumatic patients than in controls. <h3>Conclusions</h3> The evaluation of chronic pain in patients affected by rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis that display comorbid depression seems more reproducible and reliable with the use of an algometer which, therefore, could be considered an useful instrument in pain/depression overlap management. <h3>Disclosure of Interest</h3> None Declared