tbuckley/cabot-search huggingface dataset:
OC-145 Endoscopic procedure related tolerability: discomfort is worse at colonoscopy by comparison to distress at gastroscopy?
Authors: A J Irvine, M Kurien, A D Hopper, D S Sanders
Journal: Gut (2012)

<h3>Introduction</h3> Patients often find endoscopic procedures difficult to tolerate. This may reflect actual “discomfort” of the procedure (eg, due to abdominal bloating) or distress (eg, related to intubation). While previous studies have identified factors that may influence procedural tolerability, no study has tried to discriminate specifically between discomfort and distress. We sought to prospectively evaluate these outcomes in patients undergoing colonoscopy, flexible sigmoidoscopy and gastroscopy. <h3>Methods</h3> Consecutive patients attending a tertiary referral centre for clinically indicted endoscopic examination were prospectively recruited between August and December 2011. Sex, age, body mass index (BMI) and previous endoscopy experience were recorded. Procedural completion time, quality of bowel preparation and endoscopic findings were also documented. Patients were asked to grade anticipated and actual procedural discomfort and distress scores using a previously validated Numeric Rating Scale ranging form 0-10 as well as being asked to complete a Hospital Anxiety and Depression Scale. Patients also provided qualitative data, providing insights into their perceptions on perceived distress or discomfort. Data were analysed using SPSS version 19 with T-test analysis undertaken. <h3>Results</h3> 271 patients were prospectively recruited (127 male, 144 female; median 56 years, range 17–89 years). Of these, 124 patients had a gastroscopy, 116 underwent colonoscopy and 31 had flexible sigmoidoscopy examinations. 34 patients (12.5%) underwent bi-directional endoscopy. Analysis showed that discomfort scores were significantly higher in patients undergoing colonoscopy compared to gastroscopy (4.65 vs 2.90, p&lt;0.001) and also when comparing flexible sigmoidoscopy to gastroscopy (4.10 vs 2.90, p=0.047). No difference was identified when comparing flexible sigmoidoscopy discomfort levels to colonoscopy (p=0.365). Interestingly, while discomfort scores were significantly lower in the gastroscopy group, overall distress levels were significantly higher in this group compared to the colonoscopy group (3.99 vs 3.16, p=0.049). Data provided from the qualitative analysis would suggest that this is primarily due to the distress caused by oesophageal intubation. <h3>Conclusion</h3> This is the first study to discriminate between distress and discomfort in endoscopic procedures and highlights variations in tolerability dependent on the underlying procedure undertaken. Our observations provides evidence to suggest greater attention should be made by endoscopists during oesophageal intubation during gastroscopy and with regards to gas insufflation during lower gastrointestinal endoscopic examinations. <h3>Competing interests</h3> None declared.
Abstract PL03-03: The clinical significance of intratumor diversity in breast cancer
Authors: Kornelia Polyak
Journal: Cancer Research (2011)

Abstract Intratumor diversity for hereditary traits is the driver of tumor evolution, including disease progression and therapeutic resistance. To investigate the role of intratumor genetic and phenotypic heterogeneity in breast tumor progression and in therapeutic responses, we performed immunoFISH (iFISH) analyses of distant metastases from the same patient and breast tumor biopsies before and after treatment. iFISH allows for the combined analysis of phenotypic markers (e.g., such as CD24 and CD44) and chromosomal copy number gains at the single-cell level. In each tumor we evaluated four distinct tumor cell populations (CD44+/CD24-, CD44-/CD24+, CD44+/CD24+, and CD44-/CD24- cells) for chromosomal gain at 8q24 and other commonly gained chromosomal regions. iFISH data was evaluated using ecological and evolutionary models. We found high degree of genetic heterogeneity within and between the four different cell subpopulations in some tumors, in some patients the distant metastases were highly divergent, and the degree of intratumor diversity was altered by treatment and was associated with clinical characteristics. Our findings demonstrate the power of analyzing tumors as ecosystems and indicate that numerical measures of intratumor diversity can be used as clinically useful biomarkers predicting the risk of progression and therapeutic resistance. 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 PL03-03. doi:10.1158/1538-7445.AM2011-PL03-03
Potentiation of Warfarin-Induced Hypoprothrombinemia by Chloral Hydrate
Authors: Edward M. Sellers, Jan Koch-Weser, M. L. Lang
Journal: New England Journal of Medicine (1970)

During therapy with chloral hydrate one of its major metabolites, trichloroacetic acid, accumulates in plasma to more than 80 mg per liter. Trichloroacetic acid is highly protein-bound and displaces warfarin from binding sites on plasma albumin at 3 and 37°C. The resulting increase in the concentration of free plasma warfarin leads to a 25 per cent shortening of the biologic half-life of warfarin. During chronic warfarin therapy the trichloroacetic acid-induced increase in free plasma warfarin also potentiates the depression of vitamin-K-sensitive clotting-factor synthesis in the liver. Administration of 1 g of chloral hydrate daily for one week increases the hypoprothrombinemic effect of warfarin by 40 to 80 per cent. Chloral hydrate must be used with caution in patients receiving oral anticoagulants. To prevent excessive hypoprothrombinemia a reduction in warfarin requirement should be anticipated when chloral hydrate therapy is begun.
PD02-03: The Effect of Breast Conservation Therapy vs Mastectomy on Symptoms, Physical Impairments, and Function.
Authors: AH Kesarwala, LA Pfalzer, WP O'Meara, NL Stout
Journal: Cancer Research (2011)

Abstract Background: Early-stage breast cancer (BC) patients choose between breast conservation therapy (BCT) and mastectomy based on comparable recurrence rates and overall survival. In the absence of mortality benefit, consideration of anticipated functional impairments could guide decision making. Although BCT offers less extensive surgery, the administration of radiation therapy (RT) may adversely impact upper extremity (UE) function. The purpose of this analysis is to investigate the effect of BCT vs modified radical mastectomy (MRM) without RT on functional impairments among BC survivors. Materials and Methods: 196 women diagnosed with BC between 200105 were enrolled and treated in a prospective surveillance physical therapy program. 115 received either BCT, including lumpectomy and whole breast RT, or MRM without RT and were analyzed for this report. Participants’ UE range of motion (ROM), strength, and limb volume were assessed pre-operatively and at 1, 3, 6, 9, and 12+ months post-operatively by a physical therapist. Limb volume was assessed using infrared optoelectronic perometry. At 12+ months, overall health status, UE symptoms and function, and physical activity levels were reported using standardized questionnaires. Analysis of variance estimated differences in impairments and self-reported symptoms and function. One-way ANOVA analysis was used to determine significance between groups (p ≤ 0.05). Results: 65 women (57.5%) received BCT and 50 women (42.5%) received MRM. No significant differences in age, BMI, stage, ER/PR status, and number of dissected lymph nodes were found between groups. At 1 month post-operatively, shoulder internal rotation (p=0.03), abduction (p=0.01), and flexion (p=0.004) were worse in post-MRM patients, with a trend towards worse external rotation (p=0.06). A higher rate of axillary cording was seen in patients post-MRM (p=0.02). By 12+ months post-operatively, there were no differences in any of the shoulder ROM variables. BCT patients reported, however, greater weakness (p=0.03) and diminished ability to perform heavy household tasks (p=0.03). There was no significant difference between BCT vs. MRM in rates of early lymphedema (40% vs 38%) or seroma (14% vs 22%). Conclusion: Functional impairments represent an important category of morbidity for BC survivors and should be considered in pre-treatment decision making. Post-operative RT as part of BCT may not contribute significantly to impairment over the first year of treatment. The presence of self-reported weakness and difficulty performing heavy household tasks at 12+ months suggest possible future functional deficits, especially considering the potentially progressive nature of RT-associated tissue changes. Additional research is needed to assess longer-term changes and the impact of RT in the context of aggregate effects of other BC treatment modalities. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD02-03.
Surgery of the Thoracic Aorta
Authors: Nicholas T. Kouchoukos, Dimitrios Dougenis
Journal: New England Journal of Medicine (1997)

The modern surgical treatment of disorders of the thoracic aorta began in the early 1950s when Gross, Swan, Lam, and DeBakey and their associates14 reported successful treatment of coarctation and aneurysms of the descending thoracic aorta using segmental resection and replacement with several types of grafts. In 1956, Cooley and DeBakey5 reported the first successful operation for resection and graft replacement of the ascending aorta using cardiopulmonary bypass. In 1957, DeBakey and colleagues,6 also using cardiopulmonary bypass, reported the first successful resection and graft replacement of an aneurysm of the aortic arch. Since then, important advances in the diagnosis . . .
Amyloid A4 Protein and Its Precursor in Down's Syndrome and Alzheimer's Disease
Authors: Baden Rumble, Robert Retallack, Caroline Hilbich, Gail Simms, Gerd Multhaup, Ralph Martins, Athel Hockey, Philip Montgomery, Konrad Beyreuther, Colin L. Masters
Journal: New England Journal of Medicine (1989)

In patients with Alzheimer's disease, amyloid fibrils that are aggregates of A4 protein subunits are deposited in the brain. A similar process occurs at an earlier age in persons with Down's syndrome. To investigate the deposition of amyloid in these diseases, we used a radioimmunoassay to measure levels of the amyloid precursor (PreA4) in the serum of 17 patients with Down's syndrome, 15 patients with Alzheimer's disease, and 33 normal elderly controls. The mean (±SD) concentration of serum PreA4 was increased 1.5-fold in patients with Down's syndrome (2.49±1.13 nmol per liter) as compared with that in controls (1.68±0.49 nmol per liter; P<0.007); the levels in patients with Alzheimer's disease were similar to those in controls (1.83±0.78; P<0.98). We also found that the concentration of PreA4 in the brain tissue of two adults with Down's syndrome (100 and 190 pmol per gram) was higher than that in the brain tissue of either 26 patients with Alzheimer's disease (64.4± 17.3 pmol per gram) or 17 elderly controls with neurologic disease (68.5±26.3 pmol per gram). Immunocytochemical studies of brain tissue from 26 patients with Down's syndrome showed that the deposition of A4 protein amyloid began in these patients approximately 50 years earlier than it began in 127 normal aging subjects studied previously, although the rate of deposition was the same. We conclude that, since the gene for PreA4 is on the long arm of chromosome 21, which is present in triplicate in Down's syndrome, overexpression of this gene may lead to increased levels of PreA4 and amyloid deposition in Down's syndrome. However, since increased levels of PreA4 are not present in Alzheimer's disease, additional factors must account for the amyloid deposition in that disorder. (N Engl J Med 1989; 320:1446–52.)
P16.06 * EARLY PERFUSION CHANGES IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMAS TREATED WITH BEVACIZUMAB: PRELIMINARY EVALUATION BY THE PARAMETRIC RESPONSE MAP DERIVED FROM DYNAMIC CONTRAST-ENHANCED MRI
Authors: A. Vidiri, S. Marzi, F. Piludu, V. Villani, A. Antenucci, I. Terrenato, A. Fabi, A. Pace, C. M. Carapella
Journal: Neuro-Oncology (2014)

OBJECTIVE: To determine whether early monitoring of the effects of bevacizumab in patients with recurrent high-grade gliomas, by the Parametric Response Map derived from Dynamic Contrast-Enhanced MRI (DCE-MRI), may be a predictor of the response to treatment assessed through conventional MRI follow-up. METHODS: 20 patients have been enrolled in the present study. For each patient two DCE-MRI examinations, before and after the first dose of bevacizumab, were acquired. The region of interest was defined on the IAUGC (Initial Area Under Gadolinium Concentration) maps, using co-registered T1-weighted contrast-enhanced images as a guide to the tumour location. For both perfusion parameters, the parametric response map (PRM) (1) was calculated. The PRM is a voxel-wise analytic method allowing to identify and quantify the regions wherein the parameter value increased, decreased or remained stable, during or after therapy. The modifications of hyper and hypo-perfused sub-volumes, including tumour necrosis, was assessed within the lesion using a volumetric histogram analysis. The significance of changes in the different perfusion metrics, observed at baseline and during treatment, was established. The relationships between changes in perfusion and morphological MRI modifications at first follow-up were investigated. On the same patients, serial evaluations of plasma and serum VEGF levels and Von Willebrand factor (vWF) antigen were performed at the same time points. RESULTS: Early significant reductions in both IAUGC and Ktrans values, after a single dose of bevacizumab, were observed. Both the PRMs and the histogram modifications indicated the normalizing effect of bevacizumab on tumour pathological vasculature. An improvement in hypoxia after a single dose of bevacizumab seems to be predictive of a greater reduction in T1-weighted contrast-enhanced volumes at first follow-up and a better response to treatment. Circulating plasma levels of VEGF and vWF antigen significantly increased in all patients after a single dose of bevacizumab. Preliminary results showed a tendency to a significant relationship between changes in median IAUGC and in levels of vWF antigen, while no correlation was found between changes in tumour size and circulating parameters. CONCLUSIONS: Early monitoring of the modifications induced on perfusion maps, derived from DCE-MRI, as well as the variations of vWF antigen, may provide useful information to document and predict the effect of anti-angiogenic agents. REFERENCE: 1. Galbán, C.J. et al. Prospective analysis of parametric response map-derived MRI biomarkers: identification of early and distinct glioma response patterns not predicted by standard radiographic assessment. CLIN CANCER RES. 2011 Jul 15;17(14):4751-4760.
Abstract 2667: L1CAM neural adhesion molecule is overexpressed in human brain metastases of breast cancer and contributes to colony formation efficiency
Authors: Lynda M. Evans, Stephan Woditschka, Daniel P. Fitzgerald, Diane Palmieri, Sunil Badve, George W. Sledge, Patricia S. Steeg
Journal: Cancer Research (2011)

Abstract To investigate the molecular mechanisms responsible for breast cancer metastasis to the brain, a gene expression analysis was performed using formalin-fixed, paraffin embedded sections of matched primary breast tumors and resected brain metastases. The neuronal cell adhesion molecule L1CAM was upregulated by approximately 1.57 fold in the brain metastases relative to the primary tumors (p=0.037). This trend was most apparent in Her-2+ tumors (p=0.044) and did not extend to ER+ patients (p=0.42). L1CAM has been correlated to decreased patient survival in breast cancer. MDA-MB-231 breast cancer cells selected to grow in the brain (231-BR) expressed 6.4 fold greater L1CAM on western blots than the parental cell line (231-P). Using three shRNA constructs, L1CAM expression was decreased by 1.76, 3.82, and 63.3 fold in the 231-BR cell line. Decreased L1CAM expression inhibited the clonogenic formation of 231-BR cells by 40-50% (p&amp;lt;0.002); however, increased proliferation by MTT assay by 30-60% (p&amp;lt;0.002). The most efficient L1CAM knockdown also showed a 30% decrease in migration via scratch assay relative to the non-targeting control, suggesting that L1CAM may be involved in 231-BR cell migration (p&amp;lt;0.03). Studies are underway to determine the effect of L1CAM down-regulation on the development of breast cancer brain metastases. These results suggest L1CAM may be a potential novel therapeutic target for metastatic breast cancer in the brain. 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 2667. doi:10.1158/1538-7445.AM2011-2667
Service in Vietnam and Risk of Testicular Cancer
Authors: R. E. Tarone, H. M. Hayes, R. N. Hoover, J. F. Rosenthal, L. M. Brown, L. M. Pottern, N. Javadpour, K. J. O'Connell, R. E. Stutzman
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Service in Vietnam and Risk of Testicular Cancer Get access Robert E. Tarone, Robert E. Tarone * Epidemiology and Bio-statistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md. * Correspondence to: Robert E. Tarone, Ph.D., National Institutes of Health, Executive Plaza North, Rm. 407, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar Howard M. Hayes, Howard M. Hayes Epidemiology and Bio-statistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert N. Hoover, Robert N. Hoover Epidemiology and Bio-statistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jeanne F. Rosenthal, Jeanne F. Rosenthal Westat Inc.Rockville, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Linda M. Brown, Linda M. Brown Epidemiology and Bio-statistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Linda M. Pottern, Linda M. Pottern Epidemiology and Bio-statistics Program, Division of Cancer Etiology, National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Nasser Javadpour, Nasser Javadpour Surgery Branch, Division of Cancer Treatment, National Cancer InstituteBethesda, Md. Present address: N. Javadpour, 15431 Seneca Rd., Germantown, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Kevin J. O'Connell, Kevin J. O'Connell Department of Urology, National Naval Medical CenterBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ray E. Stutzman Ray E. Stutzman Present address: N. Javadpour, 15431 Seneca Rd., Germantown, Md. Present address: R. E. Stutzman, Francis Scott Key Medical Center, Baltimore, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 20, 16 October 1991, Pages 1497–1499, https://doi.org/10.1093/jnci/83.20.1497 Published: 16 October 1991 Article history Received: 13 June 1991 Revision received: 15 July 1991 Accepted: 16 July 1991 Published: 16 October 1991
Elevated F-18 FDG Uptake in the Thymus in Graves’ Disease
Authors: Yen-Kung Chen, Yen-Ling Chen
Journal: Clinical Nuclear Medicine (2003)

From the Departments of Nuclear Medicine* and Endocrinology and Metabolism,† Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan Received for publication July 1, 2002. Accepted August 13, 2002. Correspondence: Yen-Ling Chen, Department of Endocrinology and Metabolism, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wen Chang RD, Shih Lin District, Taipei, Taiwan. E-mail: [email protected]
Abstract 2185: Development and characterization of the fully human chimeric protein GrB-TWEAK targeting Fn14-positive solid tumor cells.
Authors: Hong Zhou, Mary Migliorini, Yu Cao, Lawrence H. Cheung, Walter N. Hittelman, Jeffrey A. Winkles, Michael G. Rosenblum
Journal: Cancer Research (2013)

Abstract The TNFR superfamily member Fn14, the receptor for TNF-like weak inducer of apoptosis (TWEAK), has emerged as a potentially clinically valuable target for cancer therapy. Specifically, Fn14 expression is relatively low in normal tissues but elevated in various human solid tumor types, including brain, breast, lung and melanoma, and can be a negative prognostic indicator. To target Fn14-overexpressing cancer cells, we constructed via PCR a novel chimeric protein designated granzyme B (GrB)-TWEAK, using the human TWEAK receptor-binding domain as the targeting moiety and the human pro-apoptotic serine protease GrB as the cytotoxic agent. The fusion construct was expressed in mammalian cells and purified to homogeneity from conditioned media. BiaCore analysis of TWEAK and GrB-TWEAK binding to the Fn14 extracellular domain indicated that these proteins bound to Fn14 with similar affinity, with Kds of ∼ 3 nM and ∼ 8 nM, respectively. Confocal immunofluoresence studies showed that GrB-TWEAK specifically and rapidly (within 3 hrs) internalized into Fn14-expressing MDA-MB-231 breast cancer and HT-29 colorectal adenocarcinoma cells. GrB-TWEAK activity was assessed using a panel of 26 human cancer cell lines and it demonstrated impressive and selective cytotoxicity to Fn14-expressing cells in the low nanomolar range (IC50 ranged from 0.4 nM-330 nM), which was 6- to 1117-fold more potent than free GrB. Treatment of cells expressing the multidrug resistance protein MDR1 showed no cross-resistance to the fusion construct in vitro. Mechanistic studies demonstrated that GrB-TWEAK activated caspase cascades and cytochrome C-related pro-apoptotic mechanisms consistent with the known intracellular functions of GrB in target cells. Preliminary mouse xenograft tumor model studies are ongoing. This work was conducted, in part, by the Clayton Foundation for Research (MGR) and supported by NIH grant NS055126 (JAW). Citation Format: Hong Zhou, Mary Migliorini, Yu Cao, Lawrence H. Cheung, Walter N. Hittelman, Jeffrey A. Winkles, Michael G. Rosenblum. Development and characterization of the fully human chimeric protein GrB-TWEAK targeting Fn14-positive solid tumor cells. [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 2185. doi:10.1158/1538-7445.AM2013-2185
1152IMPACT OF GENETIC CONCENTRATIVE NUCLEOSIDE TRANSPORTER VARIANTS ON PEG-INTERFERON/RIBAVIRIN THERAPY RESPONSE AND RIBAVIRIN SERUM LEVELS IN HEPATITIS C PATIENTS
Authors: M. Rau, M. Weisskopf, F. Stickel, J. Schmitt, S. Russmann, M.T. Dill, J.-F. Dufour, D. Moradpou, F. Negro, D. Semela, B. Müllhaupt, A. Geier
Journal: Journal of Hepatology (2012)