tbuckley/cabot-search huggingface dataset:
Effect of a quality program with adverse events identification on airway management during overtube-assisted enteroscopy
Authors: Luis Lara, Andrew Ukleja, Ronnie Pimentel, Roger Charles
Journal: Endoscopy (2014)

<b>Background and study aims:</b> Adverse events associated with overtube-assisted enteroscopy are similar to those with routine endoscopy. Our endoscopy quality program identified a number of respiratory adverse events resulting in emergency resuscitation efforts. The aim is to report all adverse events identified by quality monitoring and outcomes of adverse events associated with overtube-assisted enteroscopy. <b>Methods:</b> A retrospective study used data prospectively obtained from consecutive patients undergoing overtube-assisted enteroscopy between December 2008 and July 2012. Patient characteristics, medical history, procedure indication, and procedure outcomes, including diagnosis, endoscopic therapy, and complications, were obtained. <b>Results:</b> In 432 overtube-assisted enteroscopies, 15 adverse events (most frequently hypoxemia, 9 /15, 60 %) occurred in 14 patients (3.2 % of total cohort; 12 were outpatients) mostly during antegrade enteroscopy. Four patients required endotracheal intubation and 4 /12 outpatients required intensive care. The procedure was aborted in 13 /14 patients, and only 1 of 10 patients scheduled for repeat antegrade enteroscopy returned. There was no mortality. Based on the frequency of adverse events, and in consultation with anesthesia providers, from August 2012 all antegrade overtube-assisted enteroscopies at our institution were done with general anesthesia. From then till September 2013, 145 antegrade and 52 retrograde overtube-assisted enteroscopies have been done, with no adverse events. <b>Conclusions:</b> Monitoring of endoscopy practice identified adverse events associated with overtube-assisted enteroscopy. The peer-review prompted a change in practice: all patients undergoing antegrade overtube-assisted enteroscopy at our institution now have endotracheal intubation which has dramatically decreased the rate of respiratory adverse events. The impact of endoscopic quality measurements on practices, procedures, and outcomes will be of further interest.
Liver Abscess with Septic Pulmonary Emboli
Authors: H L Fred, S Basaria
Journal: New England Journal of Medicine (1997)

Figure 1. A previously healthy 52-year-old man presented with right-sided pleurisy, fever, and shaking chills for three days. On examination he was febrile and had marked tenderness to percussion over the right lower rib cage. A chest radiograph showed an elevated right hemidiaphragm and several lesions characteristic of septic pulmonary emboli in the left lower lobe (Panel A, arrows). Abdominal ultrasonography demonstrated a large, complex, predominantly hypoechoic mass in the posterior segment of the right hepatic lobe (Panel B, arrows). Contrast-enhanced abdominal computed tomography showed involvement of both the hepatic parenchyma (Panel C, arrows) and the right hepatic vein (Panel . . .
Abstract LB-306: Multiplex RT-qPCR study on the expression of stem cell markers CD24, CD44, and ALDH1 in circulating tumor cells of breast cancer patients
Authors: Areti D. Strati, Vassilis Georgoulias, Evi S. Lianidou
Journal: Cancer Research (2012)

Abstract Background: Molecular characterization of Circulating Tumor Cells (CTC) can give important information on their suspected connection to cancer stem cells. In breast cancer, putative cancer stem cells have been identified to have a CD44+CD24-/low and ALDH1+ cell phenotype. Patients and methods: We developed a tetraplex quantitative RT-qPCR assay for CD24, CD44, ALDH1 and HPRT based on the in-silico design of primers and probes with different fluorescence emission spectra. Specificity and sensitivity experiments were performed using the SKBR-3 cancer cell line. We isolated CTC from peripheral blood according to our previously described methodology (Strati et al, BMC cancer 2011) from 40 patients with early breast cancer before the administration of adjuvant chemotherapy, 23 patients with verified metastasis and 18 female healthy volunteers. We evaluated all our data with respect to CD24, CD44, ALDH1 expression of healthy volunteers using the 2βΔΔCt method. Results: In 23 patients with verified metastasis 9.0% were found to have CD44+CD24-/low phenotype and 13% ALDH1high/CD24-/low phenotype. In 40 operable breast cancer patients 8 patients (20.0%) were found to have CD44+CD24-/low phenotype and 12 patients (30.0%) were found to have ALDH1high/CD24-/low phenotype. CK-19, MAGE-A3, HER-2, TWIST1, hTERT α+β+, and mammaglobin gene transcripts were also quantified in the same samples. Discussion: Molecular characterization of CTC has shown that in breast cancer patients CTCs are partly characterized by a putative stem cell phenotype. The clinical significance of these findings in early breast cancer remains to be elucidated when the clinical outcome of these patients is known. 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 LB-306. doi:1538-7445.AM2012-LB-306
OC-084 A Comparative Study of Clinical outcomes after Laparoscopic or Open Restorative Proctocolectomy
Authors: I White, J T Jenkins, R Coomber, S K Clark, R K S Phillips, R H Kennedy
Journal: Gut (2013)

<h3>Introduction</h3> Laparoscopic colorectal surgery confers significant benefits over similar open procedures. A paucity of data exists examining this in restorative proctocolectomy, although recent literature has suggested reduced adhesions and improved fertility. We assessed consecutive patients undergoing laparoscopic ileal pouch anal anastomosis (IPAA), comparing clinical outcomes with those following conventional open surgery. <h3>Methods</h3> 207 consecutive patients undergoing IPAA between November 2006 and November 2011 were assessed [76 (37%) laparoscopic procedures and 131 (67%) open cases were included]. A careful collaborative approach to developing the new technique was undertaken during the first two years in this high volume centre. Data were collected prospectively on a dedicated database. Study endpoints included post-operative length of stay, 30 day morbidity [Clavien-Dindo classification(C-D)], readmission, reoperation, pouch function &amp; failure. <h3>Results</h3> There were no significant differences in patient age, sex, BMI or previous abdominal surgery between the two groups. Conversion rate was 9%; Median operative time was significantly shorter for open surgery – 208 (IQR 178–255) versus 285 minutes (IQR 255–325); p &lt; 0.0005. The duration of laparoscopic surgery decreased significantly during the study period. Laparoscopy significantly reduced length of stay: median 6 days (IQR 4.25–8), v 8 days (IQR 7–12); p &lt; 0.0005. Minor [C-D I/II] complications were significantly reduced with laparoscopy (32.8% v 50.4%: OR 0.48 [95%CI 0.27–0.87]). Complications [all grades] were reduced non-significantly after laparoscopic surgery There were no significant differences in total complications – 51.3% after laparoscopy versus 61.5%: OR 0.66 [95%CI 0.37–1.17], anastomotic leak rate, major morbidity, 30 day readmission, reoperation and stoma closure rates. Pouch failure has occurred in 14 patients (7.7%) overall, however there were 12 (11%) in the open group with only 2 (2.6%) in the laparoscopic group, although this is not statistically significant (P = 0.172). No significant difference was seen in pouch dysfunction rates. <h3>Conclusion</h3> Laparoscopic restorative proctocolectomy significantly reduces length of stay and minor morbidity and can be offered to an increasing proportion of restorative proctocolectomy patients. A careful collaborative developmental process has occurred in a high volume centre to achieve these results. <h3>Disclosure of Interest</h3> I. White: None Declared, J. Jenkins: None Declared, R. Coomber: None Declared, S. Clark: None Declared, R. Phillips: None Declared, R. Kennedy Grant/Research Support from: Ethicon Endosurgery and Olympus UK <h3>Reference</h3> Dindo D., Demartines N., Clavien P.A.; Classification of Surgical Complications. Ann Surg. 2004; 244: 931–937.
Abstract 4252: Activated ALK collaborates with MYCN in neuroblastoma pathogenesis
Authors: Shizhen Zhu, Jeong-Soo Lee, Feng Guo, Jimann Shin, Antonio R. Perez-Atayde, Jeffery L. Kutok, Scott J. Rodig, Donna S. Neuberg, Daniel Helman, Hui Feng, Rodney A. Stewart, Wenchao Wang, Rani E. George, John Kanki, A Thomas Look
Journal: Cancer Research (2012)

Abstract Neuroblastoma is a developmental tumor that arises in the peripheral sympathetic nervous system and accounts for 10% of all cancer-related deaths in children. The anaplastic lymphoma kinase (ALK) gene is mutationally activated in a subset of primary neuroblastomas, including those with MYCN gene amplification, suggesting pathogenic cooperation. Because the mechanism underlying this cooperation is unclear, we generated a novel transgenic zebrafish model that overexpresses human MYCN and activated ALK in the peripheral sympathetic nervous system to analyze their interaction. The expression of MYCN in this model induces neuroblastomas in the inter-renal gland, the zebrafish analogue of the adrenal medulla, which is the site of origin observed in approximately half of childhood neuroblastomas. Furthermore, the tumors resemble human neuroblastomas histologically, immunohistochemically and ultrastructurally. Concomitant expression of activated ALK with MYCN in this model profoundly accelerates the onset of neuroblastoma and markedly increases disease penetrance. Detailed in vivo analyses show that MYCN overexpression induces adrenal sympathetic neuroblast hyperplasia, blocks chromaffin cell differentiation, and triggers a developmentally-timed apoptotic response in the hyperplastic sympathoadrenal cells. Coexpression of activated ALK with MYCN provides prosurvival signals that block this apoptotic response and allow continued expansion and oncogenic transformation of hyperplastic neuroblasts. Taken together, these findings provide a mechanism for the synergistic interplay of MYCN with activated ALK in neuroblastoma pathogenesis and demonstrate the utility of the zebrafish model in understanding human disease processes that may aid the development of improved therapeutic strategies. 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 4252. doi:1538-7445.AM2012-4252
SEXUAL STERILIZATION
Authors: C. A. Baragar, Geo. A. Davidson, W. J. McAlister, D. L. McCullough
Journal: American Journal of Psychiatry (1935)

1. The Sexual Sterilization Act of Alberta was assented to March 21, 1928. 2. Up to the end of 1933, 288 cases—87 males and 201 females—had been passed by the Eugenics Board, and are dealt with in this report. Of these 206—48 males and 158 females—had at that time been operated on. 3. These operations—a vasectomy or salpingectomy—have been followed by no serious sequelæ. 4. No complaints have been received as to any change in libido or sex satisfaction, and none are expected. 5. Of the 288 cases 156, or 54.2 per cent, were diagnosed as mentally defective; 36, or 12.5 per cent, as mental deficiency with psychosis and 87, or 30.2 per cent, as otherwise psychotic and 9, or 3.1 per cent, as borderline cases including one with an exceedingly bad family history though otherwise normal. 6. Social problems, such as immorality, illegitimacy, delinquency, dependence, partial or complete, were prominent features in many of the histories. 7. Contrary to frequently expressed fears there is at present no evidence that sterilization will lead to promiscuity or a lowering of moral standards. 8. On the other hand, the treatment and training of patients and the maintenance of an adequate follow up system are still essential. 9. Facts indicating an hereditary taint or predisposition, in many cases to a startling extent, were found in 60.8 per cent of cases. 10. Sexual sterilization is undoubtedly a logical and acceptable method of coping with the great problems of mental disease and defect and their associated problems and should in properly selected and safeguarded cases be as readily resorted to as similar operations for physical disease.
Abstract 1491: Tumor-associated stromal cells increase malignancy of human colorectal cancers through epithelial-to-mesenchymal transition
Authors: Valentina Mele, Manuele Giuseppe Muraro, Diego Calabrese, Nunzia Amatruda, Francesca Amicarella, Markus Zuber, Chiara Bocelli-Tyndall, Ivan Martin, Luigi Maria Terracciano, Giulio Cesare Spagnoli, Giandomenica Iezzi
Journal: Cancer Research (2012)

Abstract BACKGROUNDS &amp; AIMS: Exogenously administered mesenchymal stromal cells (MSCs) have been shown to migrate into tumor tissues and contribute to tumor development. Still unclear is however, whether MSCs are actually a component of the stroma associated with primary tumors. The mechanisms underlying this interaction also remain to be characterized. Here we investigated the phenotype and functional properties of tumor-associated stromal cells (TASCs) isolated from human primary colorectal cancers (CRCs) and compared them with those derived from the bone marrow of healthy donors. METHODS: TASCs, isolated from CRC biopsies, and MSCs, derived from the bone marrow of healthy donors, were cultured with CRC cells from established cell lines. Proliferation, expression of epithelial-to-mesenchymal transition (EMT)-related genes and surface markers, and the release of soluble factors were evaluated. Tumorigenicity and invasive potential of CRC cells exposed to stromal cells were also investigated in vivo. RESULTS: TASCs expanded from CRC-associated stroma resembled MSCs in morphology and phenotype. Similar to MSCs, they enhanced tumor cell proliferation through the release of soluble factors, and induced upregulation of EMT-related genes on tumor cells in vitro through the expression of surface-bound TGF-beta. Conditioning by stromal cells resulted in accelerated tumor growth and increased invasiveness of CRC cells in vivo. CONCLUSIONS: The stroma associated to primary CRCs includes MSC-like cells capable of initiating EMT on CRC cells, thus contributing to tumor growth and spreading. 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 1491. doi:1538-7445.AM2012-1491
Abstract 5447: A novel inhibitor of DNA methylation
Authors: Mohammad T. Malik, Francesca M. Rinaldo, Shams Mitra, Lavona K. Casson, Wolfgang Zacharias, Sabine Waigel, Vennila Arumugam, Nazarul Hasan, Chuan Hu, Xu Bo, Gerald B. Hammond, Paula J. Bates
Journal: Cancer Research (2010)

Abstract We previously reported the discovery of XB05, a synthetic small molecule with antiproliferative activity. XB05 was found to be a strong inhibitor of DNMT1 activity in cell-free and cell-based assays. However, screening in the NCI 60 tumor cell lines and analysis using COMPARE indicated a novel mechanism of action for XB05, different from standard demethylating agents such as 5-azacytidine (azaC) and decitabine. Here, we report on new research to further characterize XB05 activity. We have examined the effects of XB05 on clonogenicity, promoter methylation, gene expression, and DNMT1 protein. XB05 was found to inhibit colony formation of HCT116 colon carcinoma cells in a dose-dependent manner with a sub-micromolar IC50. Western blots of nuclear extracts from HCT116 cells treated for 72 h with 100 nM XB05 or 10 µM azaC (as positive control) showed greatly decreased levels of DNMT1, suggesting that binding to XB05 can induce degradation of DNMT1 (previous research indicates direct drug-enzyme binding). Analysis of CDKN2A promoter methylation by bisulfite modification and sequencing demonstrated heavy methylation in untreated HCT116 cells. This was reversed by treatment of with 100 nM XB05 or 10 µM azaC, resulting in re-expression of the gene (which encodes tumor suppressor, p16), as shown by qRT-PCR. Experiments to assess promoter methylation using multiplex arrays and to examine gene expression changes using DNA microarrays were recently completed and data analysis is ongoing. To evaluate in vivo activity, we treated mice bearing subcutaneous HCT116 xenografts by IP injection of XB05 with multiple doses of up to 10 mg/kg. There was no evidence of toxicity as judged by body weights and gross necropsies. The tumors of mice treated with XB05, although not significantly smaller than in control animals, were characterized by extensive necrosis in the center of the tumor, leading to a “hollow” tumor in the majority (12/20) of mice. No similar necrosis was observed in vehicle-treated or azaC-treated mice, suggesting that this effect is treatment related. Because induced necrosis is seen with vascular disrupting agents, we also examined the effect of XB05 on endothelial cells in an in vitro assay, and observed reproducible inhibition of endothelial tube formation at 400 nM or higher. In summary, our new data confirm that XB05 is a potent inhibitor of DNA methylation in cultured cancer cells, and provide the first evidence of in vivo activity, which may involve effects on the tumor vasculature, as well as the tumor itself. 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 5447.
AB0067 Chondroitin sulfate regulates two anti-angiogenic factors in human osteoarthritic synovial fibroblasts
Authors: J. Martel-Pelletier, F. Mineau, E. Montell, J. Vergés, J.-P. Pelletier
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The symptomatic slow acting drug for osteoarthritis (SYSADOA), chondroitin sulfate, has attracted much interest as a biological agent for its use in the effective relief of disease symptoms. This is likely due to its capacity for reducing joint swelling and effusion which may be explained by its anti-inflammatory effects. However, the factors involved in this latter effect are yet to be fully identified. Angiogenesis is an important event of synovial inflammation and it is suggested to contribute to the joint symptoms in OA. <h3>Objectives</h3> We thus elected to determine the effect of chondroitin sulfate on the levels of two well-known anti-angiogenic factors previously demonstrated to be involved in OA: the vascular endothelial growth inhibitor (VEGI) and thrombospondin-1 (TSP-1). Furthermore, we explored the signaling pathways by which chondroitin sulfate exerts its effects on these factors. <h3>Methods</h3> Human OA synovial fibroblasts were obtained from sequential enzymatic digestion. Cells were pre-incubated for 18 hours with chondroitin sulfate (200 µg/ml; CS<i>b</i>Bio-<i>Active<sup>®</sup></i>, Bioibérica, Spain) and then incubated with IL-1ß (10 and 100 pg/ml) in the absence or presence of chondroitin sulfate for increasing periods of time. Cells were processed for protein expression determination using quantitative PCR, protein production using ELISAs, and for signaling pathways using Western blotting. <h3>Results</h3> Both VEGI and TSP-1 expression were dose-dependently decreased by IL-1ß at both concentrations tested. Chondroitin sulfate significantly increased the expression and synthesis levels of the two anti-angiogenic factors VEGI and TSP-1 under basal conditions as well as under IL-1ß treatment. The signaling pathways through which chondroitin sulfate increased the levels of VEGI and TSP-1 in the presence of IL-1ß were further investigated by measuring the phosphorylated levels of three MAP kinases, namely ERK1/2, p38, and JNK, and other cascades including NF-κB, Akt, and STAT-3. Data revealed that the effects occurred through two main pathways, Akt and STAT-3. Additional experiments with specific inhibitors of Akt phosphorylation (SH-6, Santa Cruz) and STAT-3 translocation (Stat3 inhibitor VIII, 5,15-DPP, Santa Cruz) confirmed these data. <h3>Conclusions</h3> This study showed that chondroitin sulfate increased the levels of two important anti-angiogenic factors, which could provide a possible new mechanism of action of this SYSADOA. These findings may explain, in part, how chondroitin sulfate reduces the severity of synovitis in knee OA. In addition, these data bring to light that anti-angiogenic factors could be targeted as a specific therapeutic approach in disease modifying OA drug development. <h3>Disclosure of Interest</h3> None Declared
Abstract 1400: Mouse models for detection of circulating tumor cells from breast cancer
Authors: Arunasalam Navaraj, David T. Dicker, Wafik S. El-Deiry
Journal: Cancer Research (2012)

Abstract Breast cancer is the most frequent malignancy among women, causing at least 373,000 deaths per year worldwide, and in United States alone an estimated 208,000 women were diagnosed with breast cancer in 2010. Recent studies indicate that breast cancer is initiated by breast cancer stem cells (BCSCs) that express CD44+/high CD24-/low surface markers. Mammospheres are non-adherent spherical cell clusters grown in selective culture conditions. Our experimental results using mammosphere cultures of different breast cancer cells such as MDA-MB-231 show drastic enrichment of breast cancer stem-like cells with the phenotype of CD44+/high CD24-/low by flow cytometry analysis. We have implanted mammosphere-derived cells into mammary fat pads of nude mice and sampled blood from such tumor-bearing animals to look for the presence of unique breast cancer cells with metastatic potential {circulating tumor cells (CTCs)}, by scoring for Epcam+/cytokeratin+/CD45- tumor cells using the FDA-approved Veridex CellSearch Sysytem. As these metastatic breast cancer cells stably express ZS-Green protein, isolated ZS-Green positive CTCs are being further subjected to breast cancer-specific multiplexed molecular marker analysis. When a mouse with the metastatic breast cancer cell line - 4T1, stained with the CellVue dye is implanted in mammary fat pads, high levels of metastasis are detected with the CellVue marker in different internal organs such as the lungs, liver, heart and lymph nodes. Fluorescence microscopy analysis of blood withdrawn from animals bearing orthotopic 4T1 breast xenograft tumors, could detect ZS-Green positive mouse breast cancer CTCs. These mouse animal models bearing xenograft tumors are facilitating our understanding of CTC detection as well as analysis methods and also in understanding of human breast cancer metastasis. Open questions we are addressing include heterogeneity of CTCs, relationships in stem cell markers and prognostic markers when CTCs are compared with the primary tumors, relationships between tumor burden and tumor aggressiveness with CTC numbers in this mouse model. In addition the model provides an opportunity for testing candidate therapeutic agents and drug combinations. 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 1400. doi:1538-7445.AM2012-1400