tbuckley/cabot-search huggingface dataset:
False-Negative Bromsulfalein Tests
Authors: Charles L. Mendenhall, Carroll M. Leevy
Journal: New England Journal of Medicine (1961)

ALTHOUGH it is widely used in evaluation of hepatic function, the validity of the bromsulfalein test has been questioned since with the standard clinical procedure1 results are occasionally negative in the presence of established liver disease. Normal values in these cases could be due to errors in dosage, improper sampling time, extrahepatic removal of the dye or preservation of bromsulfalein removal capacity despite other evidence of hepatic dysfunction. The present study was undertaken to investigate further the reason the bromsulfalein test may fail to indicate active liver disease in certain patients. Bromsulfalein and indocyanine green plasma-decay patterns, hepatic extraction, muscle . . .
Abstract 235: Beyond <i>KRAS</i> mutation status: Influence of <i>KRAS</i> copy number alteration and microRNAs in response to cetuximab in metastatic colorectal cancer patients
Authors: Leonie J.M Mekenkamp, Jolien Tol, Jeroen Dijkstra, Inge De Krijger, M Elisa Vink-Borger, Steven Teerenstra, Eugene Verwiel, Miriam Koopman, Gerrit A. Meijer, J. Han J.M. van Krieken, Roland Kuiper, Cornelis J.A. Punt, Iris D. Nagtegaal
Journal: Cancer Research (2011)

Abstract Introduction: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor (EGFR) antibodies in metastatic colorectal cancer (mCRC). Novel predictive markers are required to further improve the selection of patients for this treatment. We assessed the influence of modification of KRAS by gene copy number aberration (CNA) and microRNAs (miRNAs) in correlation to clinical outcome in mCRC patients treated with cetuximab in combination with chemotherapy and bevacizumab. Patients and methods: Formalin-fixed paraffin-embedded primary tumor tissue was used of 34 mCRC patients from a phase III trial (CAIRO2), who were selected based upon their good (n=17) and poor (n=17) progression-free survival (PFS) upon treatment with cetuximab in combination with capecitabine, oxaliplatin, and bevacizumab. Gene CNA at the KRAS locus was assessed using a high resolution genome-wide array CGH and the expression levels of 17 miRNAs targeting KRAS were determined by real-time PCR. Results: Copy number loss of the KRAS locus was observed in the tumor of 5 patients who were all good responders including patients with a KRAS mutation. Copy number gains in two wild type-KRAS tumors were associated with a poor PFS. Increased expression of several miRNAs (presented at the meeting) targeting KRAS correlated with PFS of patients treated with cetuximab, bevacizumab and chemotherapy. Conclusion: Our results indicate that the assessment of KRAS CNA and miRNAs targeting KRAS further optimize the selection of mCRC eligible for anti-EGFR therapy, in addition to KRAS mutation status. 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 235. doi:10.1158/1538-7445.AM2011-235
DIAGNOSTIC ACCURACY OF ASLA SCORE (A NOVEL CT ANGIOGRAPHIC INDEX) AND AGGREGATE PLAQUE VOLUME IN THE ASSESSMENT OF FUNCTIONAL SIGNIFICANCE OF CORONARY STENOSIS
Authors: Ravi Kiran Munnur, Liam McCormick, Brian Ko, Peter Psaltis, James Cameron, Ian Meredith, Sujith Seneviratne, Dennis Wong
Journal: Journal of the American College of Cardiology (2016)
PTU-069 Detection of cystic duct stones during laparoscopic cholecystectomy
Authors: A Kambal, T Richards, H Jayman, Z Alsallami, T Lazim
Journal: Gut (2012)

<h3>Introduction</h3> With the advent of the Laparoscopic Cholecystectomy (LC) era, the loss of tactile element hindered the detection of cystic duct stones (CDS) during surgery. These stones are implicated in the post cholecystectomy pain syndrome, failure of the insertion of intra-operative cholangiogram (IOC) catheter and the subsequent development of common bile duct (CBD) stones. The aim of this analysis is to quantify the frequency of the incidental finding of CDS during LC. <h3>Methods</h3> A cohort of consecutive patients undergoing LC during the period from November 2006 to May 2010 were included. Data were prospectively collected. Their liver function tests were documented in the preoperative period. The procedure entailed careful dissection of the cystic duct (CD) to the proximity of common bile duct. A clip was then placed at the gall bladder to CD junction. If an IOC was required, the CD was opened in the routine fashion. A partially closed endoclip was then used to milk the CD towards the gallbladder; any CDS encountered were retrieved and documented. If IOC was not indicated, the CD was milked prior to the application of gallbladder/CD clip. <h3>Results</h3> The study included 330 patients; 80 male and 250 females. Age ranged between 16 and 88 years (Median 50, IQR: 36–62). In 266 patients no CDS were detected. However, in 64 (19%) patients CDS were identified using the above technique; with 28 (45%) having a single stone. The remaining 36 (55%) patients had more than one stone with a maximum detected number of seven stones. Preoperative imaging failed to detect any CDS. Of those 64 patients with CDS, 47 (75%) showed deranged liver function tests at some stage of their disease prior to surgery. In comparison, of the 266 patients with no CDS, 152 (57%) also demonstrated abnormal liver function tests. <h3>Conclusion</h3> The results demonstrate the fact pre-operative investigations are not helpful in diagnosing CDS. Their occurrence is common. In order to detect CDS, specific intra-operative awareness and vigilance are needed. Careful upward milking of the cystic duct before applying clips is a simple, safe and effective way of detecting and extracting these stones. This study changed our practice as this procedure is now included in all our Laparoscopic chlecystectomies. <h3>Competing interests</h3> None declared.
An often forgotten cause of chest pain
Authors: Sanjin Bajgoric, William Boyd-Carson, Christopher Day, Sriram Rajagopalan
Journal: BMJ (2016)

A 66 year old white woman presented to the emergency department of a district general hospital with shortness of breath and chest pain, which radiated to her back. She had previously received antibiotics from her general practitioner for a presumed chest infection. Comorbidities included drug controlled hypertension. On examination she was tachypnoeic and hypertensive with a blood pressure of 170/90 mm Hg. No disparity in blood pressure was seen between her arms. Because clinical signs and plain chest radiography were suggestive of a left sided basal pneumonia with associated parapneumonic effusion (fig 1⇓), she received intravenous antibiotics.



Fig 1  Left pleural effusion on computed tomography (white asterisk)



Poor clinical response prompted further imaging to rule out pulmonary embolism. This identified a large distal thoracic penetrating aortic ulcer (PAU) at the level T11-12 with associated intramural haematoma (IMH) and a left sided pleural effusion (fig 2⇓). She was transferred urgently to a regional tertiary vascular centre for further management and later discharged with appropriate follow-up.



Fig 2  Axial computed tomography at different levels of the thoracic aorta (A) before and (B) after intravenous administration of iodinated contrast. (C) Sagittal multiplanar reformatted image (MPR) after iodinated contrast administration. Intramural haematoma is seen as a crescent of high attenuation within the wall of the aorta best identified before contrast administration (A; white arrows) but also seen on the MPR (C; white arrows). A large penetrating ulcer is seen in the distal descending thoracic aorta (B and C; black asterisk). A large pleural effusion is seen on the left side (A and B; white asterisk)



1.  To what group of conditions do penetrating aortic ulcers and intramural haematomas belong?

2.  What are the risk factors for these conditions?

3.  What is the most common presenting problem?

4.  What is the most appropriate diagnostic investigation?

5.  How are …
Pituitary FDG Uptake in a Patient of Lung Cancer With Bilateral Adrenal Metastases Causing Adrenal Cortical Insufficiency
Authors: Jui-Hung Weng, Jong-Kang Lee, Ming-Fang Wu, Chao-Yu Shen, Pan-Fu Kao
Journal: Clinical Nuclear Medicine (2011)

A 64-year-old woman with history of lung cancer and left adrenal gland metastasis was referred for FDG PET/CT to assess the response to target therapy and local radiotherapy treatment. In addition to bilateral adrenal gland FDG uptake lesions, the PET/CT also showed focal FDG uptake in pituitary gland with standardized uptake value of 3.9. Adrenocorticotropic hormone serum level was 439 pg/mL (normal <46 pg/mL), and serum cortisol level was 6 μg/dL (normal range, 5-25 μg/dL). The image and serum test results suggested the diagnosis of lung cancer, with bilateral adrenal metastases causing adrenal cortical insufficiency with secondary pituitary gland hyperplasia.
Evaluation de la performance et de la reproductibilité de l'endomicroscopie confocale pour la caractérisation des polypes coliques
Authors: D Le Mée, J Le Meur, J Jezequel, F Cholet, A Huguen, P Saliou, O Pennec, M Robaszkiewicz
Journal: Endoscopy (2012)

L'endomicroscopie confocale (EMC) a été conçue pour analyser in vivo et à l'échelle microscopique la muqueuse digestive au cours d'un examen endoscopique et permettre un diagnostic instantané. L'objectif principal de l'étude était d'évaluer la performance de l'EMC dans la caractérisation des polypes colorectaux par rapport au gold standard qui est l'examen anatomopathologique. Les objectifs secondaires étaient d'évaluer la reproductibilité de cette technique et la correspondance entre des caractéristiques décrites à l'examen endomicroscopique et les diagnostics histologiques.
Abstract 3279: Enhanced <i>in vivo</i> inhibition of neuropeptide-mediated castration resistant prostate cancer progression by combination therapy with enzalutamide and saracatinib.
Authors: Joy C. Yang, Hao G. Ngyuen, Allen C. Gao, Christopher P. Evans
Journal: Cancer Research (2013)

Abstract Introduction: It has been shown that overexpression of the neuropeptides gastrin-releasing peptide (GRP) in LNCaP cells renders the cells castration-resistant through both androgen receptor (AR) activation and intracrine androgen biosynthesis. Aberrant activation of AR by GRP is mediated through Src kinase activation, which may be inhibited by the specific SFK inhibitor saracatinib. Inhibition of cognate AR activation requires anti-androgen. We hypothesize that treatment of this kind of CRPC demands the combination of saracatinib and new generation anti-androgen enzalutamide (MDV-3100). Materials and methods: LNCaP GRP-Pro cells grown in CS medium were treated with control, saracatinib (2 μM), enzalutamide (10 μM) or the combination. Cell proliferation over 7 days was monitored by MTT assays. Cell cycle distributions over 72 hours of treatment were analyzed by flow cytometry. Cells were collected to prepare nuclear and cytosolic lysates respectively and examined by Western Blotting analysis for AR, pSrc, pAkt, LC-3 and β-actin. Expression of full-length AR and variants were compared by RT-qPCR. Orthotopic injection of GRP-Pro cells into castrated SCID male mice was used as the animal model for drug treatment studies. Results: Enzalutamide or saracatinib alone only slightly inhibited CR cell growth but the combination brought it down to 27% of the control. Apoptosis was also enhanced with the combination. Enzalutamide only inhibited AR nuclear translocation in regular serum-kept GRP-Pro cells, while saracatinib inhibited the translocation in CS conditions. In the orthotopic model, neither treatments with saracatinib (25 mg/kg/daily) or enzalutamide (10 mg/kg/daily) alone showed any effect on tumor take, tumor weight or serum PSA levels. However, the combination treatment drastically reduced the tumor weights (0.66±0.13 g for controls vs. 0.24±0.07 g for the combo) and serum PSA levels (120.79±27.87 ng/ml vs. 19.19±7.45 ng/ml). Conclusions: For GRP mediated CRPC growth, neither saracatinib or enzalutamide alone is sufficient to inhibit AR translocation and tumor progression. Combination of the two significantly improved the treatment for the CRPC orthotopic tumor model. Citation Format: Joy C. Yang, Hao G. Ngyuen, Allen C. Gao, Christopher P. Evans. Enhanced in vivo inhibition of neuropeptide-mediated castration resistant prostate cancer progression by combination therapy with enzalutamide and saracatinib. [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 3279. doi:10.1158/1538-7445.AM2013-3279
Laboratory-confirmed invasive meningococcal disease: effect of the Hajj vaccination policy, Saudi Arabia, 1995 to 2011
Authors: Z Memish, R Al Hakeem, O Al Neel, K Danis, A Jasir, D Eibach
Journal: Eurosurveillance (2013)

Saudi Arabia (SA) experienced two large invasive meningococcal disease (IMD) outbreaks during the 2000 and 2001 Hajj pilgrimages. In 2002, polysaccharide quadrivalent ACWY vaccines became mandatory for Mecca and Medina pilgrims/residents older than two years. This study aimed to analyse IMD surveillance data among citizens, residents and pilgrims in SA from 1995 to 2011, focusing on changes before and after the new vaccination policy. For all laboratory-confirmed IMD cases in the national surveillance database from 1995 to 2011, serogroup and age were retrieved. The cases' seasonal distribution as well as the case fatality ratios (CFR) were obtained. For Saudi citizens/residents and Hajj pilgrims, annual rates were calculated using mid-year population estimates. The Student's t-test was used to compare means between the pre-epidemic (1995-1999) and post-epidemic (2002-2011) periods, excluding outbreak years. From 1995 to 2011, laboratories notified 1,103 cases. Between the pre- and post-epidemic periods, mean annual IMD rates decreased from 0.20 (standard deviation (SD): 0.1) to 0.06 cases/100,000 (SD: 0.06; p=0.02), mean numbers of Hajj-related cases from 13 (SD: 9.3) to 2 cases/year (SD: 2.3; p=0.02) and the mean age from 31 (SD: 1.3) to 18 years (SD: 1.4; p<0.01). The CFR in Saudi citizens (10.4) was lower than among foreign pilgrims (28.9) and decreased from 19.3% (SD: 1.8) in the pre-epidemic to 11.4% (SD: 7.0; p=0.04) in the post-epidemic phase. The decrease of annual IMD rates, CFR and Hajj-related cases between the pre- and post- vaccine era suggests a possible positive effect of the mandatory ACWY vaccination for pilgrims/residents in Mecca and Medina. Regular surveillance with an annual data analysis is necessary to monitor trends and circulating serotypes and to implement appropriate public health measures to avoid new IMD epidemics during upcoming Hajj seasons.
Abstract 4345: AZD8055, a combined TORC1/TORC2 inhibitor regulates Mycn protein expression and prevents neuroblastoma growth in vitro and in vivo
Authors: Lynsey S. Vaughan, Karen Barker, Hannah Webber, Yann Jamin, Simon Robinson, Sylvie Guichard, Louis Chesler
Journal: Cancer Research (2011)

Abstract Neuroblastoma is the most common and deadly solid tumour of childhood (Brodeur, 2003). Amplification of the MYCN oncogene occurs in 25% of NBs correlating with poor clinical outcome. High risk neuroblastoma responds to current therapies but rapidly acquires chemoresistance; therefore alternative treatment strategies are required. Because of the importance of MYCN amplification in high risk neuroblastoma and specific expression of Mycn protein in tumour tissue, we have examined indirect methods of destabilising Mycn by targeting key components of upstream signalling pathways, responsible for maintenance of Mycn protein levels. Mycn protein stability is maintained by the RAS (RAF/MEK/ERK) and PI3K (PI3K/AKT/mTOR) pathways. The mammalian target of rapamycin (mTOR) plays an important role in cell proliferation, metabolism and tumourigenesis, and is frequently altered in cancer. Rapamycin and its analogues target the TORC1 complex and are effective against tumour xenografts but are limited by consequent up regulation of PI3K activity. Inhibition of TORC1 alleviates a TORC1 dependent negative feedback loop, with resulting activation of PI3K and AKT-dependent survival pathways. AZD8055 is an mTOR kinase inhibitor that inhibits both TORC complexes with IC50 values in the nanomolar (nM) range. Treatment of N-myc wild-type or phosphomutant expressing neuroblastoma cell lines with AZD8055 inhibited mTOR-dependent phosphorylation of key pathway components, coincident with selective inhibition of wild-type but not phospho-mutated N-myc protein. Cell proliferation was reduced and sensitive cells accumulated in G1 as shown by flow cytometric analysis. Cells expressing N-myc phosphomutant proteins showed less sensitivity to AZD8055, with GI50 values above mechanistic range for targeted effects of this drug. The ability of AZD8055 to inhibit neuroblastoma tumour progression was tested in a transgenic model of neuroblastoma (TH-MYCN) that over expresses Mycn protein and is predisposed to spontaneous tumour formation (Weiss, 97). We present data showing that AZD8055 inhibits tumour progression, reduces tumour cell proliferation and targets the mTOR complex in vivo. In conclusion, inhibition of mTOR signalling is highly effective against MYCN-driven cell lines and tumours, and therefore could be a promising therapeutic strategy for targeted treatment of MYCN-amplified neuroblastoma. 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 4345. doi:10.1158/1538-7445.AM2011-4345
Antiplatelet and Anticoagulant Agents in Hereditary Hemorrhagic Telangiectasia
Authors: Hannah L. Devlin, Anna E. Hosman, Claire L. Shovlin
Journal: New England Journal of Medicine (2013)

Patients with hereditary hemorrhagic telangiectasia are prone to serious nosebleeds, so many physicians withhold therapy that would normally be administered for serious thrombosis. A survey showed that over 40% had received low-dose aspirin without increased bleeding risk.
SAT0154 MRI evaluation of the knees in assessing rhuematoid arthritis patients on etanercept:
Authors: T. Tsuchida
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Biologics improved Rheumatoid Arthritis (RA) treatment dramatically and we have abundant evidence on its high efficacy, especially on preventing joint destruction. However, we do not have enough evidence on its efficacy in halting progression of weight bearing joint destruction. There is a study reporting that biologics can stop joint destruction under Larsen Grade (LG) II, while joint destruction continues for LG III and IV. <sup>1</sup> <h3>Objectives</h3> In our experiences, we have many cases that required total knee arthroplasty (TKA) even when baseline LG was II or lower. X-ray may not be sensitive enough to detect inflammation, but Magnetic Resonance Imaging (MRI) can detect inflammation more accurately and precisely. MRI evaluation is expected to play a role in predicting prognosis early, which may possibly prevent TKA. We therefore hypothesized that the MRI findings on RA knees lower than LG II will give additional prediction on the severity of inflammation and chances of TKA. <h3>Methods</h3> We performed retrospective analysis on RA patients with knee complaints at our institution. Inclusion criteria include patients treated on Etanercept with knee symptoms and underwent MRI evaluation before Etanercept was initiated. We analyzed the relationship between baseline MRI findings (presence of synovitis, T1 low/T2 high) and the chances of having TKA despite Etanercept treatment. <h3>Results</h3> We identified total 116 RA patients on Etanercept, and TKA was performed in total 35 knee joints of 28 patients among them. TKA was performed in 12.3% of the patients in LG 0-II, and 45.5% in LG III, IV, which showed statistically significant difference (p&lt;0.001). Those knee joints in LG0-II with MRI findings suggesting synovitis underwent TKA significantly more often than those without MRI findings (16.4%, 4.9%, p=0.0496). Similarly, baseline LG0-II joints with and without T1 low, T2 high signals showed statistical difference in the frequency of TKA (34.5% vs 0.0%, p&lt;0.001) (Table 1). <h3>Conclusions</h3> Once the knee joint destruction progress to LG III and IV in RA patients with knee complaints, joint destruction continues and more often results in TKA. RA patients with knee complaints would be benefited from MRI evaluation before biologics treatment, even if the knee X-ray suggests LG0-II. If MRI suggests synovitis or T1 low, T2 high findings, the disease may progress to joint destruction. We advocate MRI is a necessary test in order to predict prognosis. We also advocate that Etanercept treatment needs to be initiated in the earliest stage possible, ideally before progression to LG II. <h3>References</h3> Seki E, et al. Clin Rheumatol 2009;28:453-460 <h3>Disclosure of Interest</h3> None Declared
Palpitations after Dinner
Authors: Kazutaka Kurokohchi, Osamu Imataki
Journal: New England Journal of Medicine (2014)

A 76-year-old woman with rheumatoid arthritis, diabetes, and hypertension presented with palpitations that occurred only after she had eaten dinner. The sensation was felt at the center of the chest and lasted for 10 to 15 minutes after the meal.
1036 A COMPARATIVE STUDY TO DETERMINE THE MOST USEFUL RESPONSE EVALUATION CRITERIA IN HEPATOCELLULAR CARCINOMA PATIENTS TREATED WITH MOLECULAR TARGETED THERAPY
Authors: H. Takeda, Y. Osaki, E. Iguchi, S. Ako, T. Inuzuka, J. Nakajima, F. Matsuda, A. Sakamoto, S. Henmi, K. Hatamaru, S. Saito, A. Nasu, H. Nishikawa, R. Kita, Y. Okabe, T. Kimura
Journal: Journal of Hepatology (2012)
Abstract 5295: Near-infrared fluorescence <i>in vivo</i> tumor imaging using SNAP-tag technology
Authors: Haibiao Gong, Joy Kovar, Aihua Zhang, Ivan R. Correa, Ming-Qun Xu, Michael Olive
Journal: Cancer Research (2011)

Abstract The SNAP-tag is a small protein derived from the human DNA repair protein O6-alkylguanine-DNA-alkyltransferase (hAGT). It reacts with fluorescent dye conjugated benzylguanine (BG) substrate, leading to covalent labeling of the fluorescent dye on the SNAP-tag®. This property makes the SNAP-tag a valuable tool for fluorescence imaging. In this study, we extended the SNAP-tag technology to near-infrared (NIR) fluorescence imaging using IRDye® 800CW conjugated BG substrate (BG-800). Compared to the visible spectrum, fluorescence in the NIR spectrum has the advantage of low light absorption and reduced autofluorescence, which is highly desirable for in vivo imaging. We created HEK293, MDA-MB-231, SK-OV-3 and SK-BR-3 cells stably expressing SNAP-ADRB2 fusion protein. The ADRB2 potion of the protein directs the localization of the protein to the cell membrane. The expression of SNAP-ADRB2 was confirmed by the reaction between BG-800 substrate and the cell lysate. Microscopic examination confirmed that SNAP-ADRB2 was localized on the cell membrane. The signal intensity of the stable cells after reaction with the substrate BG-800 was dependent on the BG-800 concentration. In vivo imaging study showed that BG-800 could visualize xenograft tumors established with SNAP-ADRB2 overexpressing SK-OV-3 cells. These results demonstrated that the application of SNAP-tag technology could be extended to in vivo imaging when combined with NIR fluorescent fluorophores. 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 5295. doi:10.1158/1538-7445.AM2011-5295