tbuckley/cabot-search huggingface dataset:
Investigators, Insurers Consider Marrow Transplant Issues
Authors: E. Blume
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Investigators, Insurers Consider Marrow Transplant Issues Get access Elaine Blume Elaine Blume Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 16, 21 August 1991, Pages 1136–1138, https://doi.org/10.1093/jnci/83.16.1136 Published: 21 August 1991
Abstract 3692: Allyl isothiocyanate arrests bladder cancer cells in mitosis, and mitotic arrest in turn leads to apoptosis via Bcl-2 phosphorylation
Authors: Feng Geng, Li Tang, Yuesheng Zhang
Journal: Cancer Research (2011)

Abstract Allyl isothiocyanate (AITC) occurs in many common cruciferous vegetables, and was recently shown to be selectively delivered to bladder cancer tissues through urinary excretion and to inhibit bladder cancer development in an orthotopic rat bladder cancer model. Here, we show that AITC arrests human bladder cancer cells in mitosis and induces apoptosis. Mitotic arrest by AITC was associated with significant down regulation of both α-tubulin and β-tubulin which are essential for mitosis. AITC also induced mitochondria-mediated apoptosis, including cytochrome c release from mitochondria to cytoplasm, cleavage of caspase-9 and caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP) and lamin B1, and formation of TUNEL-positive cells. Both a general caspase inhibitor (Z-VAD-FMK) and a caspase-9 inhibitor (Z-LEHD-FMK) attenuated AITC-induced apoptosis. Moreover, we found that apoptosis induction by AITC resulted from mitotic arrest and was mediated via Bcl-2 phosphorylation at Ser70. Thus, AITC-induced mitotic arrest was accompanied by a strong Bcl-2 phosphorylation, while Bcl-2 expression was not affected. Pre-arresting cells in G1 phase using hydroxyurea abrogated both mitotic arrest and Bcl-2 phosphorylation in cells treated with AITC. Overexpression of a Bcl-2 mutant (loop domain deleted, removing Ser70) prevented AITC from inducing apoptosis. AITC-induced Bcl-2 phosphorylation appears to be mediated by c-Jun N-terminal kinase (JNK), as AITC activated JNK but a JNK inhibitor (SP600125) abolished Bcl-2 phosphorylation in AITC-treated cells. In summary, AITC is a highly promising agent for bladder cancer prevention and treatment, and the present study reveals a novel anticancer mechanism of AITC in human bladder cancer cell. 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 3692. doi:10.1158/1538-7445.AM2011-3692
Ixabepilone and cyclophosphamide as neoadjuvant therapy in HER2-negative breast cancer with exploratory Onco<i>type</i> DX assessments: A Sarah Cannon Research Institute phase II trial.
Authors: N. W. Peacock, D. A. Yardley, C. B. Hendricks, S. Y. Huh, S. L. Ketchum, C. Chao, C. Yoshizawa, M. Shastry, B. Strike, H. A. Burris, J. D. Hainsworth
Journal: Journal of Clinical Oncology (2011)

1066 Background: Ixabepilone (Ixa) is active in taxane-refractory metastatic breast cancer as well as in the neoadjuvant setting where Ixa yielded a pathologic complete response (pCR) rate of 18%. In this study, we evaluated Ixa in combination with cyclophosphamide (Cyc) as neoadjuvant treatment for HER2-negative breast cancer. The primary endpoint was pathologic complete response (pCR) rate, defined as no residual cancer in breast or lymph nodes. Responses were correlated with Oncotype DX recurrence scores. Methods: Eligible women were HER2-negative (IHC 0-1+ or FISH negative), node positive or T > 2 cm with inflammatory and T1N0 tumors excluded. Patients (pts) received Ixa 40mg/m2 with Cyc 600 mg/m2 day 1 of each 21-day cycle. Following 6 cycles, pts went to surgery. Postoperative radiation and hormonal treatments were at discretion of the treating MD. Core biopsies (pretreatment and at surgery) were analyzed using the Oncotype DX RT-PCR assay; the associations between recurrence scores and clinical responses were investigated in an interim analysis. Results: 156 women have been enrolled. Baseline characteristics for the first 78 pts are reported (median age 52 years; 86% invasive ductal; 50%/33% T2/T3; 41% triple negative). 50 pts have undergone surgery. 14 pts discontinued treatment early (disease progression – 6; pt/MD request – 5; toxicity – 3).Grade 3/4 toxicity included: neutropenia (69%), leukopenia (51%), neuropathy (9%), and febrile neutropenia (6%). The pCR rate was 18%. Higher pretreatment recurrence scores (>31) were associated with higher pCR rate (p=0.025) in 38 patients with available data. Non-significant trends were observed for ER and PR by RT-PCR, but not for HER2. None of these measures were predictive of clinical tumor responses after 3 or 6 cycles of therapy, although assessment methods varied across timepoints. Conclusions: Ixabepilone with cyclophosphamide as neaodjuvant therapy is feasible and active. Tumors with higher Oncotype DX recurrence scores at baseline were more likely to achieve pCR.
Endoscopic intraductal radiofrequency ablation of remnant intrapapillary mucinous neoplasm with acute hemorrhage after incomplete surgical resection
Authors: Jochen Weigt, Ane Kandulski, Peter Malfertheiner
Journal: Endoscopy (2014)

An 83-year-old woman presented with recurrent hemosuccus pancreaticus. The patient had previously undergone a distal pancreatic resection due to intrapapillary mucinous neoplasm, with main duct involvement of the tail. Upper endoscopy revealed active bleeding through the ampulla of Vater. During a previous episode of pancreatic bleeding, intraductal injection of fibrin glue had been performed.
FRI0085 Prediciting rheumatoid arthritis by autoantibody testing (PRERA): Preliminary results of a community-based investigation
Authors: M.E. Jimenez Boj, R. Bauer, M. Gaertner, V.P. Nell-Duxneuner, T.A. Stamm, O. Wagner, K.P. Machold, J.S. Smolen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A characteristic feature of RA is the presence of autoantibodies (AAB) such as rheumatoid factor (RF), anti-RA33, and antibodies to citrullinated peptides (ACPA) in a majority of patients. RF and ACPA are not only diagnostically helpful but are also prognostic indicators for progression of joint destruction. Over the past years, health care research has increasingly focused on early diagnosis and even prevention. Since RA is a disease of significant morbidity, affecting app. 0,5 - 1% of the population and leading to progressive disability as well as individual and societal costs, pre-emptive recognition of the disease or at least of a high risk to develop RA could help for planning optimal therapeutic measures. <h3>Objectives</h3> Given that certain AAB are highly specific for RA and may precede the disease by many years, antibody testing in healthy individuals could prove helpful for evaluation of the risk to develop RA and for designing innovative therapeutic strategies that attempt to interfere with the disease process at a very early time point. In this prospective study we determined AAB in healthy individuals presenting to community health centres for pre-emptive health screening to investigate the prevalence of ACPA, RF, and anti-RA33 in the population and to subsequently determine the incidence of RA in AAB-positive individuals compared to AAB-negative persons over a period of five years. <h3>Methods</h3> Blood drawn at the time of the screening examination was anonymously analyzed for the presence of AAB. All AAB positive individuals as well as age and sex matched AAB negative persons were invited to attend the outpatient clinic for a thorough rheumatological examination and follow-up. <h3>Results</h3> 3059 Sera were obtained over a period of 22 months; 178 (5,8%) were positive: 95 (3,1%) for RF, 82 (2,6%) for ACPA, and 4 (0.1%) were positive for both AAB; among the RF positive individuals, almost 21% (0,6% of the total population) had high titer RF (&gt;50IU/ml). Among the patients who subsequently attended a rheumatological examination, none had signs of inflammatory joint disease; however, none of the participants of this ongoing study has been followed for more than 18 months. <h3>Conclusions</h3> Among healthy individuals, there is a prevalence of AAB of 5,8%. 0,6% of the total population with high titer RF and 0.8% ACPA with little overlap of RF and ACPA. None of these persons had evidence of an inflammatory joint disease. Follow up examinations will reveal the potential of these AAB to reverse to negative or persist, and/or the potential of AAB positive patients to develop RA. Acknowledgement. This study was supported by a grant from the National Bank (OENB). <h3>Disclosure of Interest</h3> None Declared
Superior Imaging Qualities of Tc-99m MAG-3 in Captopril Renal Scintigraphy Contributing to the Detection of Branch Artery Stenosis
Authors: DONALD W. TREPASHKO, DAN G. PAVEL, JOHN D. PORT
Journal: Clinical Nuclear Medicine (1996)

The use of captopril renal scintigraphy for the detection of renovascular hypertension secondary to branch renal artery stenosis and renal interlobar arterial diseases is well documented when using Tc-99m DTPA and I-131 Hippuran. The advent of Tc-99m MAG-3 has improved significantly the image quality, enabling the unequivocal detection of a branch renal artery stenosis in the case of a 34-year-old woman with acute onset of hypertension. The Tc-99m MAG-3 captopril study demonstrated striking retention of radiopharmaceutical exclusively in the superior pole of the left kidney, which was not identified on time-activity curve. The single branch artery stenosis was confirmed by renal angiography. This example reinforces the necessity to consider both images and curves, and emphasizes the significant benefit of MAG-3 in detecting branch abnormalities.
FRI0026 Interleuikin-32 induces tnfalpha and type i interferon via proteinase 3 - protease activated receptor 2-tir-domain-containing adapter-inducing interferon-beta axis
Authors: M. Nakayama, Y. Niki, T. Kawasaki, Y. Takeda, Y. Toyama, T. Miyamoto
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Interleukin (IL)-32 is known to exert adujvant effects on innate immune response and has an important role in inflammatory disease, such as rheumatoid arthritis [1]. However, receptors and downstream signaling pathways remain to be clarified, except for a role of proteinase 3 (PR3)-binding protein [2]. Although it was also speculated that protease activated receptor-2 (PAR2) mediated the activity of IL-32 through PR3 [3], there is a paucity of reports dealing with the relationship between IL-32 and PAR2. <h3>Objectives</h3> We have investigated about the potential signaling pathway of IL-32-TNFα or type I interferon axis was analyzed <i>in vitro</i>. <h3>Methods</h3> Using THP-1 cells, <i>in vitro</i> effect of exogenous IL-32γ on TNFα or IFN-β, one of the type I interferon, production was assessed with or without PMSF, inhibitor for serine proteases. And it was also assessed with or without siRNA against PR3 or PAR2. In another experiments, siRNA against TIR-domain-containing adapter-inducing interferon-beta (TRIF), downstream signaling of PAR2 [4], or TRIF-related adaptor molecule (TRAM), which was the molecule recruited by TLR4 to bind TRIF [5], was administered to THP-1 with IL-32γ and TNFα or IFN-β production was assessed. <h3>Results</h3> In human monocyte cell line, THP-1 cells, exogenous IL-32γ alone was capable of stimulating TNFα and IFN-β production, which was markedly diminished by either addition of PMSF or siRNA against PR3 or PAR2. Furthermore, siRNA against TRIF, but not TRAM, also hampered IL-32γ-induced TNFα or IFN-β production. Collectively, IL-32-PR3 interaction may be profoundly bound to PAR2-TRIF axis, not TLR4-TRAM-TRIF axis, followed by robust TNFα and IFN-β production, since PAR2 reportedly sensed serine proteases such as PR3. <h3>Conclusions</h3> IL-32 induces TNFα and type I interferon via PR3-PAR2-TRIF axis and may play an important role in inflammatory disease. <h3>References</h3> Kim SH, et al. Interleukin-32: a cytokine and inducer of TNF-alpha. <i>Immunity</i>, 22, 131-142 (2005). Novick D, et al. Proteinase 3 is an IL-32 binding protein. <i>Proc Natl Acad Sci U S A</i>, 103, 3316-3321 (2006). Dinarello CA, et al. IL-32, a novel cytokine with a possible role in disease. <i>Ann Rheum Dis.</i> 65 Suppl 3:iii61- iii64 (2006). Rallabhandi P, et al. Analysis of proteinase-activated receptor 2 and TLR4 signal transduction: a novel paradigm for receptor cooperativity. J Biol Chem 283:24314-24325 (2008). Yamamoto M, et al. TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat Immunol 4: 1144-1150 (2003). <h3>Disclosure of Interest</h3> None Declared
PTH-148 Does Glasgow Blatchford Score or Pre-Endoscopy Rockall Score Identify Low Risk Patients following upper Gastrointestinal Haemorrhage? a New Zealand Perspective: Abstract PTH-148 Table 1
Authors: I A Murray, M R Johnston, H Leung, H Norton, J-Y Park, T Fesaitu, C Baines, E Fawcett, A Salleh, P McLeod, N R O’Donnell, W Zhang, J A García, M Schultz
Journal: Gut (2013)

<h3>Introduction</h3> Upper gastrointestinal haemorrhage (UGIH) is a common medical emergency worldwide. The Glasgow Blatchford (GBS) and pre-endoscopy Rockall (PERS) scores are used to predict outcome and need for intervention. This retrospective study aims to determine their value in a mixed rural and urban population in New Zealand. <h3>Methods</h3> GBS and PERS were determined for all adult patients admitted with UGIH to our teaching hospital between January 2007 and November 2011. Need for therapy (endoscopic, blood transfusion or surgery), 30-day mortality and 14-day re-bleed rate were recorded and the optimum scoring system for predicting low risk patients determined by logistic regression. The Lower South Regional Ethics Committee approved the study. <h3>Results</h3> There were 424 admissions with UGIH: data was complete for 388 admissions to enable PERS and GBS calculation. Median age was 74.3 years, 55.1% were male and the majority were New Zealand European (85.8%). Commonest findings were oesophagitis, gastritis, duodenitis (43%), peptic ulcer (35.3%), hiatus hernia (16.8%), normal (11.9%), varices (4.8%) and malignancy (3.1%). 181 cases (46.6%) received an intervention, of which 75 (19.3%) had an endoscopic intervention, 147 (37.9%) a blood transfusion, 8 (2.1%) surgery and 7 (1.8%) an iron infusion. 30-day mortality was 4.6% (18 patients) and 14-day re-bleed rate was 6.0% (23 patients). GBS &lt; 1 predicted low risk (no intervention, re-bleed or mortality), accounting for only 3.1% of all admissions (14 patients). 42 (10.8%) had a PERS of 0 but intervention was required in 15 (35.7%). A further 193 patients had outpatient gastroscopy for UGIH and 113 had inpatient bleeds during the study period. <h3>Conclusion</h3> GBS (of &lt; 1) is superior to PERS in identifying low risk patients who could be safely managed as outpatients following UGIH saving health resources. Despite having less patients with varices we had fewer low risk patients than British studies. Low risk patients may have been triaged to outpatient endoscopy by Primary Care. <h3>Disclosure of Interest</h3> None Declared.
SP0164 Mechanical strain and arthritis: Lesson from an animal model of spondyloarthritis
Authors: D. Elewaut
Journal: Annals of the Rheumatic Diseases (2013)

Over the past years, it has become clear that Tumor Necrosis Factor (TNF) is a key player in the pathogenesis of spondyloarthritis, a disease leading to joint inflammation of axial skeleton and peripheral joints, but the mechanisms by which this occurs are only partially known. Particularly, the cellular targets sufficient to mediate the articular and extra-articular manifestations (gut and skin inflammation) of spondyloarthritis remained to be defined, as well as the cellular constituents capable of modulating this TNF driven inflammation. Recently, mesenchymal cells were found to be principle targets for TNF in a mouse model of spondyloarthritis, characterized by enhanced TNF mRNA stability, resulting in Crohn's like ileitis as well as peripheral arthritis. Hence, TNF-R1 expression on mesenchymal cells was sufficient to mediate combined gut and joint pathologies in this model of murine spondyloarthritis. Strikingly, in the earliest phase of disease, inflammation was found to be restricted to enthesial sites. Using a variety of strategies we found that mechanical strain is an important contributor to the disease pathogenesis in this model. Overall, the data suggest an essential role of mechanotransduction in the onset of spondyloarthritides. <h3>Disclosure of Interest</h3> None Declared
FRI0135 Is statin use in patients with rheumatoid arthritis consistent with EULAR recommendations?
Authors: T. Eidner, T. Neumann, G. Wolf, P. Oelzner
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> According to the EULAR recommendations for cardiovascular (CV) risk management in patients with rheumatoid arthritis (RA), statins belong to the preferred treatment options. <h3>Objectives</h3> To evaluate statin use in RA patients in daily practice in comparison to EULAR recommendations according to individual cardiovascular risk. <h3>Methods</h3> We studied 245 consecutive patients with rheumatoid arthritis from our university rheumatological outpatient department. The following data were collected: age (&gt;40 years), gender, duration of disease, RF/CCP-antibody-status, lipid-status, blood pressure/use of antihypertensive drugs, comorbidities (diabetes mellitus – Dm, cardiovascular diseases), smoking history, use of statins. For RA patients with Dm or established cardiovascular disease (Coronary heart disease, peripheral or cerebrovascular arterial occlusive disease) an indication for statin use was postulated. In patient without these comorbidities, an indication for statin use was supposed in case of a 10-year-risk for cardiovascular events of at least 10% according to the SCORE-algorithm [1] and the EULAR-recommendations [2]. <h3>Results</h3> Diabetes mellitus and/or a cardiovascular disease were comorbidities in 62 of 245 RA patients (25,3%; f/m 35/27); 37 of them were treated with statins (59,7%). In 183 patients without these comorbidities the assumed 10-year-risk for severe cardiovascular events according to the SCORE-algorithm accounted for: –at least 15% in 16 pts. (8,7%), –between 10 and 15% in 30 pts. (16,4%), –between 5 and 10% in 59 pts. (32,3%) and –under 5% in 78 pts. (42,6%). From 46 pts. with a risk-score of at least 10% only 7 pts. (15,2%) were treated with statins. <h3>Conclusions</h3> In RA patients with diabetes mellitus or established cardiovascular disease, statins are a common comedication. In contrast, in patients without these comorbidities but with high cardiovascular risk statins are only rarely used. In consideration of the increased cardiovascular risk of RA patients and the current treatment recommendations, every patient should be examined for the individual cardiovascular risk including reassessing the indication for statin use at least yearly. Therefore, a tight cooperation between rheumatologist and general practitioner is required. <h3>References</h3> Conroy et al.; Eur Heart J 2003;24:987–1003. Peters et al.; Ann Rheum Dis 2010 69: 325-331. <h3>Disclosure of Interest</h3> None Declared
PTU-072 A UK standardised cystic duct identification technique will help to mitigate the effect of human error and improve systematic training
Authors: C Brown, R Radwan, A Rasheed
Journal: Gut (2012)

<h3>Introduction</h3> Laparoscopic cholecystectomy is a visual discipline and biliary tract anatomy is deduced by visual clues from a displayed image on a TV Screen where errors stemming from visual illusions and misperceptions are possible and even when irregularities were identified, corrective feedback does seem to occur, which is characteristic of human thinking under firmly held assumptions lead to misidentification of the bile duct as a cystic duct and consequent misadventure. Our aim was to survey descriptive terms of cystic duct identification and compare them against the Society of the American Gastrointestinal and Endoscopic Surgeons recommendations being the only written guidance in the literature. <h3>Methods</h3> Welsh trainees and ALS members were invited to complete a online survey to select the descriptive terms that best fit their method of cystic duct identification including Calot9s triangle Identified”, “Calot9s triangle Demonstrated”, “Infundibular technique utilized” and “Critical View of safety demonstrated”. <h3>Results</h3> 133 surveys were completed by six clinical fellows (4.5%), 28 ST/SpRs (21.2%) and 98 consultants (74.2%). The most common descriptive terms used was “Calot9s triangle demonstrated” (38.3%), followed by “Calot9s triangle identified” (32.5%), “critical view of safety demonstrated” (24.2%) and lastly “infundibular technique utilized” (5%). The majority of surgeons in this survey do not seem to select the terms that are perceived to reflect “best practice” for the method of cystic duct identification during LC. It is possible that these surgeons are utilising “best practice” but did not recognise the provided terms or selected the incorrect term or used other terms that were not provided in this survey. <h3>Conclusion</h3> The survey highlights the need for standardisation of image-guided surgical procedures to mitigate the effect of human error and take the outcome of such surgery a new height that was never reached in the open era. Standardisation will also permit systematic training and streamline competency testing paving the way for the transition from apprenticeship-based training to a systematic time-efficient training. In the aviation industry the initial study into human factors was controversial but is now a mandatory and cornerstone process for achieving best air transport safety. We feel there is potential for adopting a similar approach in the rapid and technologically advancing era of surgery based on “visual disciplines” to help reduce human error and thus leading to improved patient safety. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Sockeel P</b>, Chatelain E, Massoure MP, <i>et al.</i> Surgeons can learn from pilots. <i>J Chir (Paris)</i> 2009;<b>146</b>:250–5.