tbuckley/cabot-search huggingface dataset:
PMO-244 Infliximab reduces the need for correction of fistulae and drainage of abscesses: a UK retrospective study of Crohn's disease patients
Authors: C D Wheeler, R Chipperfield, T Orchard, J Lindsay
Journal: Gut (2012)

<h3>Introduction</h3> Crohn9s disease affects 50–100 patients per 100 000 in the population and typically follows a progressive course, with fistulae occurring in 17% to 43% of patients. The most common type of fistulae, perianal, have been shown to decrease quality of life and increase the likelihood of total colectomy. This retrospective study assessed incidence of procedures to correct fistulae and drain abscesses for a UK cohort of patients being treated with infliximab. <h3>Methods</h3> 18 UK centres participated in the study, including data from a total of 380 individuals with Crohn9s disease who had received their first infusion of infliximab after 1 January 2003. Patients were eligible for inclusion with 12 months data prior to, and 24 months data post infliximab initiation, in their clinical record. Data on all investigations, clinic appointments, admissions and operations were extracted from the patient record in a standardised manner by members of the local clinical team. A prespecified statistical analysis plan compared healthcare resource utilisation at 12, 18 and 24 months after the introduction of infliximab with resource utilisation during the 12 months prior to starting treatment. <h3>Results</h3> In the 12 month period before initiation of infliximab therapy there were a total of 32 procedures within the study population to correct fistulae, treat severe anal fistulae or drain abdominal or peri-rectal abscesses. In the 24-month period following initiation of infliximab therapy there were significantly fewer cumulative procedures (13 total). Procedures undertaken for correction of fistulae reduced from 12 (3.2% of patients) in 12 months pre-infliximab to 7 (1.9% of patients) in the 24 months following infliximab initiation (p&lt;0.05). Treatment of severe anal fistulae was reduced from six cases (1.6%) to 2 (0.5%) (p&lt;0.01). Procedures undertaken to drain either abdominal or peri-rectal abscesses reduced from 14 (3.7%) to 4 (1.1%) over the same period (p&lt;0.0001). <h3>Conclusion</h3> In a large UK cohort of Crohn9s disease patients, treatment with infliximab was shown to significantly reduce the need for surgical procedures relating to either fistulae correction or drainage of abscesses <h3>Competing interests</h3> C Wheeler: Employee of: MSD, R Chipperfield Employee of: MSD, T Orchard: Grant/Research Support from: MSD, Warner Chilcott, Johnson and Johnson, Consultant for: Warner Chilcott, Ferring, Shire, Speaker bureau with: Warner Chilcott, Ferring, Shire, J Lindsay: Grant/Research Support from: MSD, Abbott, Shire, Consultant for: MSD, Abbott, Shire, GSK, Ferring, Warner Chilcott, Atlantic Healthcare, Speaker bureau with: MSD, Abbott, Shire, Ferring, Warner Chilcott.
Accumulation of Ga-67 Citrate in a Tuberculous Splenic Abscess
Authors: PAN-FU KAO, KAI-YUAN TZEN, YU-HSIANG CHOU, SZU-YU LU, DONG-LING YOU
Journal: Clinical Nuclear Medicine (1996)

A case of 65-year-old man with tuberculous splenic abscess is presented. The Ga-67 citrate scan revealed three focal areas of increased uptake in the left upper quadrant of the abdomen. The combined Tc-99m SC/Ga-67 scans revealed that these Ga-67 avid lesions localized in the splenic photon-deficit areas found in the Tc-99m SC scan. This case demonstrated the usefulness of Ga-67 imaging in a survey of fever of unknown origin in unsuspected tuberculous splenic abscess.
Blood Coagulation in Thyroid Dysfunction
Authors: Joseph V. Simone, Charles F. Abildgaard, Irving Sghulman
Journal: New England Journal of Medicine (1965)

SIGNIFICANT elevations of antihemophilic factor (AHF, factor VIII) have been reported to accompany strenuous exercise,1 2 3 epinephrine infusions,3 , 4 fever induction,5 pregnancy,6 intravascular hemolysis,7 treatment with progestational agents,8 renal failure,9 hyperglobulinemia,10 treatment with prednisone11 and, recently, hyperthyroidism.12 It was the purpose of this investigation to study the coagulation mechanism in the hyperthyroid and hypothyroid states and to measure the changes in the levels of coagulation factors in response to specific therapy.Materials and MethodsPatientsCoagulation studies were performed on 32 patients with clinical disorders of thyroid function. Twenty-five patients had hyperthyroidism as documented by clinical manifestations and by elevation of the . . .
P99 Pulmonary Rehabilitation in Interstitial Lung Disease Patients: Effects on Maximum Exercise Capacity, Anxiety and Depression
Authors: MM Peasey, SS Kon, D Dilaver, JL Canavan, MG Ng, SE Jones, AL Clark, MI Polkey, WD-C Man
Journal: Thorax (2012)

<h3>Background</h3> There is increasing evidence to support the use of Pulmonary Rehabilitation (PR) in patients with Interstitial Lung Disease (ILD). Several studies have shown significant improvements in six minute walk distance and health related quality of life measures, such as the Chronic Respiratory Disease Questionnaire (CRQ), following PR <i>(Holland et al; 2008)</i>. However there is a paucity of data surrounding other outcome measures such as maximal walking exercise tests (the incremental shuttle walk: ISW) or anxiety and depression levels. As the ISW and the Hospital Anxiety and Depression scale (HAD) are commonly used outcome measures in UK PR programmes, the aim of the study was to assess the response of these outcomes to PR in the ILD population. <h3>Methods</h3> We analysed outcome data in 62 (30 male:32 female) consecutive ILD patients completing an 8-week outpatient PR programme. Diagnoses were idiopathic pulmonary fibrosis (n=29), connective tissue related ILD (n=8), sarcoidosis (n=14), hypersensitivity pneumonitis (n=3), asbestosis (n=4), drug induced ILD (n=4). Pre- and post-PR data was analysed using either Paired T-Tests or Wilcoxon Tests. <h3>Results</h3> Baseline mean (standard deviation) age was 70(11) years, FVC 69 (22)% predicted and median (25th, 75th centiles) MRC dyspnoea score was 4 (3, 4). There was a significant improvement in ISW (95% confidence intervals 31, 69 metres), HAD-Anxiety (95% CI –0.8, –2.4) and HAD-Depression (95% CI –0.7, –2.3). There were also significant improvements in all domains of the CRQ. <h3>Conclusion</h3> The ISW and HAD scores are responsive to PR in patients with ILD.
Safety and efficacy of endoscopic submucosal dissection of rectal tumors extending to the dentate line
Authors: Kenichiro Imai, Kinichi Hotta, Yuichiro Yamaguchi, Tomoaki Shinohara, Shohei Ooka, Kei Shinoki, Naomi Kakushima, Masaki Tanaka, Kohei Takizawa, Hiroyuki Matsubayashi, Takuma Oishi, Hiroyuki Ono
Journal: Endoscopy (2014)

<b>Background and study aims:</b> Unique anatomical features render endoscopic resection for rectal tumors extending to the dentate line (RTDL) technically challenging. The aim of this study was to evaluate the feasibility of endoscopic submucosal dissection (ESD) for RTDLs. <b>Patients and methods: </b>This retrospective study compared ESD for RTDLs with proximal rectal tumors between September 2002 and June 2012. En bloc resection rate, R0 resection rate, complications, and tumor recurrences were assessed. <b>Results:</b> A total of 45 RTDLs (median age 69 years; 15 males; median lesion size 38.4 mm) and 94 proximal rectal tumors were identified. En bloc resection and R0 resection rates were 95.6 % (43/45) and 53.3 % (24/45), respectively. The perforation rate was 4.4 %. Compared with proximal rectal ESD, ESD for RTDLs showed longer procedure time (104 vs. 60 minutes; <i>P</i> < 0.001), lower R0 resection rate (53.3 % vs. 70.2 %; <i>P</i> = 0.019), and more frequent high grade fever (22.2 % vs. 4.3 %; <i>P</i> = 0.002). No residual adenoma was observed at the first surveillance colonoscopy. Recurrence rate did not differ significantly between the two groups. <b>Conclusions:</b> ESD for RTDLs demonstrated safety and effectiveness comparable to ESD in proximal rectal lesions.
AB0516 An open-label randomized controlled study to evaluate the efficacy of etanercept (ETN) versus rituximab (RTX), in patients with active rheumatoid arthritis previously treated with RTX and TNF blockers:
Authors: B. Combe, M. Dougados, I. Logeart, C. Lukas, X. Mariette, X. Puechal, A. Saraux, T. Schaeverbeke
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In patients with active RA and inadequate response to several lines of biologics including TNF blockers and RTX, there is no recommendation for therapeutic strategy. It has been suggested that the changes in the immune reaction after B-cell depletion may facilitate the efficacy of previous therapies such as TNF blockers. <h3>Objectives</h3> To evaluate efficacy and safety of retreatment with ETN + MTX versus an additional course of RTX + MTX, in RA patients who experienced inadequate response to ETN then RTX. <h3>Methods</h3> This open-label, multicentre, randomized study was designed to include patients with active RA (DAS28&gt;4.4) and previous inadequate response to one or two courses of RTX in the last 6-9 months and to at least one TNF blockers including ETN. Patients received ETN (50 mg/week) + MTX or RTX (1 g x 2) + MTX during 6 months. The sample size calculation was based on 20-30% EULAR responders in the RTX group versus 45-55% in the ETN group which required inclusion of 110 patients. <h3>Results</h3> The study was stopped after one year due to recruitment failure. Twenty patients (10 in each group) were randomised and followed during 6 months. The efficacy results are reported on the table. One severe adverse event related to treatment was reported in the RTX group (severe infusion reaction). <h3>Conclusions</h3> This controlled study confirms preliminary reports of cases and suggests that a retreatment with ETN in RA patients who previously failed TNF blockers then RTX, could be efficient. <h3>Disclosure of Interest</h3> B. COMBE Grant/Research support from: PFIZER, M. DOUGADOS Grant/Research support from: PFIZER, I. LOGEART Employee of: PFIZER, C. LUKAS Grant/Research support from: PFIZER, X. MARIETTE Grant/Research support from: PFIZER, X. PUECHAL Grant/Research support from: PFIZER, A. SARAUX Grant/Research support from: PFIZER, T. SCHAEVERBEKE Grant/Research support from: PFIZER
Abstract 5655: Infectivity selective oncolytic adenovirus for pancreatic cancer by redesigning the AB-loop via adenovirus library screening
Authors: Yoshiaki Miura, Julia Davydova, Masato Yamamoto
Journal: Cancer Research (2012)

Abstract A number of cancers, including pancreatic cancer, are resistant to adenovirus (Ad) infection. Genetically coded viral capsid modification has achieved increased infectivity but not much target specificity. Direct selection of targeted vector from Ad library is a promising approach to overcome this issue. We have established a novel Ad vector generating system enabling a huge-size Ad library. We hypothesize that Ad with redesigned AB-loop isolated by the screening of the new library system would result in a new class of oncolytic adenovirus with selective infectivity for the therapy of pancreatic cancer. Ad AB-loop library was screened with mesothelin-expressing 293 cells (293-MSLN) to target mesothelin (MSLN) which is highly over-expressed in pancreatic cancer, and the clones converged to one dominant clone. The binding of Ad with selected clone was analyzed with 293, Panc-1, MiaPaCa-2, A549 and 293-MSLN. The binding was significantly higher in 293-MSLN than any other cells and corresponded to the order of MSLN-expression by FACS analysis. The anti-MSLN siRNA and antibody significantly reduced the binding to MSLN expressing cells. The binding ability of the virus with this motif in Panc-1 was higher than that of Ad with 5/3 modified fiber which is known to exhibit remarkably enhanced infectivity pancreatic cancer cells. The anti-tumor effect was analyzed in vivo using Panc-1 as a MSLN-positive and MiaPaCa-2 as a MSLN-negative subcutaneous tumors. The injection of the selected clone showed significant anti-tumor effect against Panc-1 tumors, and almost complete regression of some Panc-1 tumors was observed, while it didn't demonstrate anti-tumor effect against MiaPaCa-2 tumors. The hexon immunostaining and the intratumoral viral copy number also indicated that the selected clone replicated in MSLN-positive pancreatic cancer, but not in MSLN-negative cancer. In this study, we selected MSLN targeting Ad vector from the high throughput screening of Ad library by infectivity. The selected clone exhibited significant infectivity to MSLN-positive pancreatic cancer cells in vitro and in vivo. This new genetically modified oncolytic Ad with selective infectivity to pancreatic cancer may embody next generation targeted therapeutics for this devastating disease. 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 5655. doi:1538-7445.AM2012-5655
Case 24-2004
Authors: Myles D. Keroack, Ruben Peralta, Simeon D. Abramson, Joseph Misdraji
Journal: New England Journal of Medicine (2004)

A 48-year-old man had had a 33-month history of intermittent abdominal pain and black stools containing occult blood. Endoscopic and imaging studies of the upper and lower gastrointestinal tract revealed no abnormalities. Video-capsule endoscopy revealed a mucosal lesion in the distal ileum. A diagnostic procedure was performed.
Abstract LB-31: Drug combination studies: theory and analysis
Authors: Mark S. Hixon
Journal: Cancer Research (2010)

Abstract A novel method for the graphical analysis of drug combination studies is presented. This method, Delta Plot Analysis, addresses the shortcomings of Isobolograms and Combination Index determinations. By use of this method, one may choose either a Bliss Independence or Loewe Additivity model and conduct the analysis. The method is comparative in nature, plotted as a function of cell survival (tracking other observables is also possible), and most importantly contains confidence intervals for determining significance above/below an additive effect line. In short, assay data with much scatter require greater differentiation from additivity to be interpreted as anything other than additive while data with less scatter allow one to conclude synergy or antagonism with less deviation from theoretical additive. Notably, the method handles partial response curves and makes use of single agent dose response curves to incorporate experimental uncertainty. A great advantage of the method is that synergistic and antagonistic interactions produce signature patterns in addition to providing data points falling outside of the additive effect confidence interval - something of great utility to the analyst. Also intriguingly, when accounting for experimental uncertainty (through simulations or with empirical data), a synergistic interaction is revealed to be synergistic regardless of the choice of Bliss or Loewe models. Delta Plot Analysis has been validated with published data and confirmed with in-house drug combination studies. The method is robust, requires no specialized software and easily depicts a multidrug combination study. This presentation also includes a look at the theory behind multiple drug interactions from a first principles perspective and provides a useful way of connecting drug action with drug effect. 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-31.
Abstract 3707: Design and characterization of a double packaged system for localized drug delivery for the treatment of cancers
Authors: Eva C. Williams, Ryan Toomey, Marcia Gordon, Donald Williams, Dave Morgan, Norma Alcantar
Journal: Cancer Research (2010)

Abstract This research aims at developing a drug delivery system that will provide a plethora of benefits such as cost effectiveness, reduction of toxicity and a control over the release of chemotherapeutic drugs in brain and ovarian cancer patients. We have designed a model drug delivery system consisting of non-ionic surfactant vesicles (niosomes) packaged within a biodegradable, temperature and pH sensitive hydrogel (chitosan) network. Optimization of the release rates were accomplished by altering the condition of its two components, chitosan and niosomes. Two main cancer drugs, Paclitaxel and Carboplatin, were used for encapsulation. It was found that medium molecular weight chitosan with a crosslinker: chitosan ratio of 4:1, which corresponded to a pH of 7.4, resulted in the finest controlled release. Surface characteristics, such as the interaction between the niosomes and chitosan were determined using Surface Forces Apparatus. The system was also tested in-vivo in mice models, where the success of the drug delivery has been measured by measuring the drug concentrations of the mice blood with respect to time and by analyzing shrinking effects in induced cancer tumors in mice. Xenogen was used to visualize the release of drugs in-vivo. Release rates of this system have been compared with other delivery methods. Our results will help in the development of low cost and improved methods for drug delivery with applications to brain tumors and intracavitary ovarian cancer treatments. 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 3707.
Case 20-2008
Authors: Herbert L. Bonkovsky, Peter Siao, Zulmarie Roig, E. Tessa Hedley-Whyte, Thomas J. Flotte
Journal: New England Journal of Medicine (2008)

A 57-year-old woman was admitted to the hospital because of abdominal pain and weakness, 1 month after gastric bypass surgery. In the month after the operation, episodes of tachycardia, bradycardia, diarrhea, dark urine, and abdominal pain occurred, with urine cultures that were positive for bacteria. After admission, weakness and numbness in the legs and arms developed and progressed to flaccid quadriparesis. A diagnostic test was performed.
P132NFAT3/GATA4 facilitates the NHE1 mediated induction of osteopontin in H9c2 cardiomyoblast
Authors: M Mlih, N Abdulrahman, F Mraiche
Journal: Cardiovascular Research (2014)

Osteopontin (OPN) is a secreted protein involved in cardiac remodeling and hypertrophy induced by the expression of angiotensin 2 (ANG II). Transgenic mice lacking OPN in the heart prevent cardiac hypertrophy and fibrosis mediated by ANG II. ANG II is an activator of the Na+/H+ exchanger isoform 1 (NHE1), a plasma membrane protein that regulates intracellular pH and also implicated in cardiac hypertrophy. Interestingly, transgenic mice expressing active NHE1 developed spontaneous cardiac hypertrophy in association with elevated levels of osteopontin. Whether ANG II induces osteopontin expression via activation of NHE1 remains unknown.

ANG II (100 nM, 16h) induces cardiomyocyte hypertrophy associated with an increased OPN protein expression ( ANG II: 138% ±30%, p<0.05). ANG II stimulated cardiomyocyte hypertrophy and OPN protein expression regressed in the presence of the NHE1 inhibitor, EMD (10μM) and calcineurin inhibitor, FK506 (1μM). H9c2 cells infected with the active form of NHE1 showed that NHE1 activation is enough to induce the hypertrophic pathway NFAT3/GATA4 and OPN expression. These effects were prevent by FK506. Our results demonstrate that NHE1 activation, either using an active NHE1 or through induction with ANG II, induces NFAT3 translocation into the nucleus and also demonstrate a significant activation of the transcription factor GATA-4 (NHE1: 149% ±28%, p<0.05). The activation of GATA-4 and OPN protein expression induced by active NHE1 is inhibited by FK506 treatment.

These results suggest that NFAT3/GATA4 pathway is a critical component of the NHE1 hypertrophic pathways activated by ANG II in cardiomyoblast and plays a key role in the regulation of cardiomyocyte hypertrophy and OPN protein expression.
P2-15-07: The Need for Additional Surgeries to Adequately Excise Early Breast Cancers May Have a Negative Impact on Local Recurrence.
Authors: R Warburton, L Alriyees, DY Wang, SL Wong, W Leong
Journal: Cancer Research (2011)

Abstract Background: Breast conservation surgery (BCS) is considered the standard of care for the treatment of early stage breast cancer (ESBC, AJCC stage 1 and 2). 20 to 50% of patients will require further surgery for positive or close margins. There is recent data suggesting that re-operation can have a negative impact on local and distant recurrences. Our aim is to examine the effects of multiple surgeries to obtain adequate margins on breast cancer recurrence, metastatic disease and survival. Methods: We reviewed a prospectively maintained breast cancer database at the University Health Network and included all women who had BCS for their first diagnosis of ESBC between January 2004 and December 2007. Patients with neoadjuvant chemotherapy were excluded. We collected patient demographics, surgical pathology, adjuvant therapy and follow up outcome data, which included local recurrence, distant recurrence, cancer-specific survival and overall survival. Clinical and pathologic features were compared using chi-square analyses. Patients who had one lumpectomy were compared to those who had multiple surgeries by using Kaplan-Meier survival curves and log rank test. Results: Of a total of 744 patients (8 patients had bilateral cancer) 577 (77.6%) had one lumpectomy only (Group 1). 167 (22.4%) patients required further surgery (group 2 = LR+LM+LRM): 83 (11.1%) had a re-excision (LR), 69 (9.3%) had mastectomy (LM) and 15 (2%) had a re-excision followed by a mastectomy (LRM). Thus, a total of 85 (11.4%) patients had mastectomy to achieve adequate margins. All clinicopathologic factors and adjuvant systemic treatments were similar between the two groups except for age and use of adjuvant radiotherapy, which was related to that fact that many of those in group 2 had mastectomy. We observed a difference in disease-free survival favoring patients with lumpectomy only (group 1–3.4% vs. group 2–8.1%, p= 0.01) but there was no difference in distant metastasis (4.5% vs. 5.6%, p=0.56), cancer-specific survival (97.6% vs. 95.6%, p=0.20) and overall survival (6.9% vs 6.3%, p= 0.76) at a median follow up of 4.54 years. Conclusion: Despite having similar stage, grade, receptor status and adjuvant systemic therapies, having multiple surgeries for primary breast cancer appeared to be associated with decreased disease-free survival but had no difference in rates of distant metastatic disease, cancer-specific survival and overall survival. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-07.