tbuckley/cabot-search huggingface dataset:
OC-155 No way back—irrevocable alteration of the gastric and oesophageal micro-environment following cholecystectomy
Authors: S N S Gilani, G Bass, T N Walsh
Journal: Gut (2012)

<h3>Introduction</h3> <b>Background:</b> Loss of the gallbladder reservoir function at cholecystectomy may critically alter the dynamics of bile storage and release. Consequent iatrogenic duodeno-gastro-esophageal reflux (DGER) may be associated with oesophago-gastric adenocarcinoma. <h3>Aims</h3> To examine the histological and molecular effects of cholecystectomy-induced DGER on gastric and oesophageal mucosae. <h3>Methods</h3> <b>Patients and Methods:</b> In a retrospective study we compared 26 gallstone-free controls with 25 patients pre-cholecystectomy and 29 patients post-cholecystectomy for one or more years. In a prospective study we compared 26 controls with 25 patients before and within 1 year of cholecystectomy. All underwent oesophago-gastro-duodenoscopy (EGD) with biopsies from the antrum, esophagogastric junction (EGJ) and 5 cm above the EGJ. A histochemical bile reflux index (BRI) was calculated and immunohistochemistry was performed for p53 and Ki67. <h3>Results</h3> <b>Results:</b> In the retrospective study antral BRI positivity was 11% in controls vs 69% in cholecystectomy patients (p=0.001); at the EGJ BRI positivity was 19% in controls vs 41% in cholecystectomy patients (p=0.032). p53 was expressed at the antrum in 4% of controls vs 52% cholecystectomy patients(p=0.001) and in 19% vs 66% at the EGJ (p=0.001). Ki67 was expressed at the antrum in 23% vs 59% (p=0.001) and at the EGJ in 19% vs 62% (p=0.001). Prospectively, BRI positivity increased from 11% to 36% (p=0.04) at the antrum within 1 year of cholecystectomy. Ki67 expression increased from 19% to 48% (p=0.044) at EGJ in patients within 1 year of cholecystectomy while p53 remained unchanged. <h3>Conclusion</h3> Changes attributable to DGER occur early in the gastric and LES mucosae of patients following cholecystectomy. Ki67 and p53 over-expression suggests that these changes may be precursors of malignant transformation. Such concerning changes suggest that options other than cholecystectomy be considered for patients with gallstones in a functioning gallbladder. <h3>Competing interests</h3> None declared.
AB0147 A study of adipokines’ level in patients affected by systemic sclerosis
Authors: M. Vasile, E. Neumann, U. Mueller-Ladner, K. Stefanantoni, D. D’Aluisio, G. Valesini, V. Riccieri
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Systemic sclerosis (SSc) is a connective tissue disorder characterized by progressive fibrosis of the skin and remodeling of the microvasculature. Increased extracellular matrix deposition by fibroblasts affects most internal organs. Adipokines such as adiponectin, resistin and leptin are immunomodulatory cytokine-like mediators (1). They seem to be able to contribute to the tissue damage in some connective tissue diseases but little is known about their role in SSc (2). <h3>Objectives</h3> The present study analyzed adipokines' levels in the sera of SSc patients and their possible correlations with clinical parameters <h3>Methods</h3> Blood samples of 59 SSc patients and 23 healthy controls were collected. Adiponectin and resistin were measured by commercially available ELISA kits, while leptin was measured by a Bioplex Pro Assay kit. In all patients modified Rodnan Skin score (mRSS), nailfold capillaroscopy, number of digital ulcers, cardiac, lung, articular and gastrointestinal involvements were evaluated. <h3>Results</h3> We found a trend to lower adiponectin levels in SSc patients in comparison to healthy controls (13.577 mg/ml vs 15.31 mg/ml; p&lt;0.07) whereas resistin levels were significantly lower (12.88 pg/ml vs 16.02 pg/ml; p&lt; 0.03) while leptin levels were significantly higher (57.88 ng/ml vs 17.63 ng/ml; p&lt;0.004). Moreover we found significantly lower adiponectin levels in those patients with a higher skin score (14.651 mg/ml vs 11.316 mg/ml; p&lt;0.05). A trend to decreased levels of adiponectin was also observed in patients with digital ulcers and with articular involvement (10.912 mg/ml vs 1.5 mg/ml, p&lt;0.07; 11.653 mg/ml vs 15.414 mg/ml, p&lt;0.07 respectively). <h3>Conclusions</h3> In SSc patients adipokines serum levels differ from those of healthy subjects. Adiponectin and resistin seem to be down-regulated, as if they could have a protective role, as confirmed by a higher skin score in those cases with lower adiponectin levels. Besides leptin is up-regulated, confirming its role as a potentially pro-inflammatory cytokine in many connective tissue diseases (3). However their different behavior deserve deeper investigations to better understand their role in SSc <h3>References</h3> Lago F, Dieguez C et al 2007<b>:</b> Adipokines as emerging mediators of immune response and inflammation. <i>Nature Clinical Practice Rheumatology 2007, vol. 3: 716-24.</i> Lakota K, Jun W et al 2012: Levels of adiponectin, a marker for PPAR-g activity, correlate with skin fibrosis in sistemi sclerosis: potential utility as biomarker? <i>Arthritis Research&amp;Therapy 14:R102</i> Vadacca M, Margiotta D et al 2008. Adipokines and Systemic Lupus Erythematosus: Relationship with Metabolic Sindrome and Cardiovascular Disease Risk Factors<i>. J Rheumatol 36:295-7.</i> <h3>Disclosure of Interest</h3> None Declared
Hydroxyurea for Patients with Essential Thrombocythemia and a High Risk of Thrombosis
Authors: Sergio Cortelazzo, Guido Finazzi, Marco Ruggeri, Oscar Vestri, Monica Galli, Francesco Rodeghiero, Tiziano Barbui
Journal: New England Journal of Medicine (1995)

Abnormalities in the number and function of platelets may contribute to thromboembolic complications in patients with essential thrombocythemia. We assessed whether maintaining the platelet count below 600,000 per cubic millimeter with hydroxyurea reduces the incidence of thrombosis in patients with essential thrombocythemia and a high risk of thrombosis.
Pylephlebitis as a Complication of Diverticulitis
Authors: Fernando Bazan, Marcos Busto
Journal: New England Journal of Medicine (2015)

A 45-year-old man presented with fever and jaundice. A CT scan showed acute perforated sigmoid diverticulitis; in addition, there was gas in the inferior mesenteric vein extending to the splenic vein up to the origin of the portal vein, a finding consistent with pylephlebitis.
Abstract 1746: Expression of the translation regulatory protein RBM3 is associated with a favourable prognosis in epithelial ovarian cancer
Authors: Ehlén Åsa, Donal J Brennan, María Alvarado-Kristensson, Björn Nodin, Darran J O'Connor, Mathias Uhlén, Fredrik Pontén, Karin Jirström
Journal: Cancer Research (2010)

Abstract Background: RNA binding proteins are important regulators of gene expression involved in various post-transcriptional processes like mRNA stability and translation. We have recently demonstrated that high expression of RBM3 is associated with a favourable prognosis in breast cancer. Aims and Methods: The aim of the present investigation was to examine the prognostic value of RBM3 in epithelial ovarian cancer (EOC). For this purpose, protein expression of RBM3 was examined by immunohistochemistry in tumour samples from 154 prospectively collected EOC cases (Cohort I). In addition, RBM3 gene expression was examined in an independent cohort with 282 EOC cases (Cohort II). Results: No significant correlation was seen between RBM3 protein expression and any established prognostic clinicopathological parameters. However, survival analysis revealed a significant association between RBM3 nuclear expression and prolonged survival (HR=0.633, 95% CI=0.421-0.952, p=0.028) in cohort I. This association did not remain significant in multivariate analysis. In line with the IHC data, high RBM3 mRNA levels were associated with prolonged survival in Cohort II in both univariate (HR=0.671, 95% CI=0.504-0.894, p=0.006) and multivariate (HR=0.751, 95% CI=0.562-1.004, p=0.053) analysis. Conclusion: In accordance with our previously studies of breast and colon cancer, high nuclear expression of RBM3 was associated with improved survival in patients with ovarian cancer. Further investigations are needed in order to understand the role of RBM3 in tumour progression and to confirm the utility of RBM3 as a prognostic biomarker in various cancer forms. We are currently investigating the role of RBM3 in cisplatin response in ovarian cancer cell lines. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 1746.
Contribution of immature muscle precursors to myositis pathogenesis: a source of type I interferon and a possible target of the immune attack
Authors: A Tournadre, V Lenief, A M Beaufrére, Assia Eljaafari-Dany, P Miossec
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To investigate the contribution of immature muscle precursors to the adaptive and innate immune responses in inflammatory myopathy. <h3>Method</h3> Muscle biopsies from eight patients with polymyositis and dermatomyositis were investigated for the expression of CD56, a marker of immature muscle precursors, HLA class I, known to be overexpressed in myositis, and interferon β (IFNβ), a type I IFN, inducer of HLA class I and possibly involved in the pathogenesis of myositis. Muscle inflammatory infiltrates were further characterised for the presence of myeloid dendritic cells (mDCs) and their associated C type lectin receptors (CLRs), which play a critical role in initiating adaptive immune response, and for the products of activated DCs, IL12 and IL23. In vitro, the production of IFNβ by human myoblasts was assessed after stimulation with the TLR3 agonist Poly(I:C), IFNγ and IL17. The expression of HLA class I by myoblasts was determined by FACS after TLR3 stimulation and IFNβ neutralisation. <h3>Results</h3> Positive IFNβ staining was detected in seven of the eight myositis patients whereas no positive staining was detected in the five controls. Although rare IFNβ expression was observed in mononuclear cells, a strong staining was observed in muscle fibers with a perifascicular pattern in DM and an intrafascicular pattern in PM. Staining of serial PM and DM sections identified IFNβ-positive muscle fibers as immature muscle precursors expressing CD56 and HLA class I. In contrast to controls, expression of DC-SIGN, MMR, ASGPR, the main CLRs associated with DCs, was broadly observed in myositis with an endomysial pattern in PM and a perivascular pattern in DM. Overexpression of CLRs was associated with the presence of CD11c+mDCs and with the presence of IL12 and IL23 cytokines. Serial immunostaining performed in five patients showed that inflammatory infiltrates with CD11c-positive DCs expressing CLRs were associated with the presence of CD56- and HLA class I-positive muscle fibers. In vitro, IFNβ production was induced when TLR3 activation was combined with IFNγ stimulation. TLR3 activation up-regulated HLA class I expression which was decreased after IFNβ neutralisation. <h3>Conclusion</h3> In myositis muscle tissue, immature muscle precursors were identified as a local source of type I IFN. In turn, such a local production of IFNβ could be implicated in HLA class I overexpression on muscle cells. Moreover, immature muscle precursors may represent the target of an immune response involving activated DCs, with expression of CLRs and production of IL12 and IL23 cytokines implicated in the Th1 and Th17 polarisation.
Midazolam with meperidine and dexmedetomidine vs. midazolam with meperidine for sedation during ERCP
Authors: Zhenzhen Xu, Yaqi Zhai, Dongxin Wang
Journal: Endoscopy (2014)

We read with interest the prospective, double-blind, randomized study by Lee et al. [1], on comparing the sedative effect and adverse events of midazolam + meperidine + dexmedetomidine with those of midazolam + meperidine during endoscopic retrograde cholangiopancreatography (ERCP). The authors’ conclusion that the addition of dexmedetomidine to the midazolam + meperidine regimen provided better sedative efficacy during ERCP is significant to clinical practice for painless choledochoscopy procedures. However, we would like to make the following comments on the study.
Hepatitis B Vaccine in Medical Staff of Hemodialysis Units
Authors: Wolf Szmuness, Cladd E. Stevens, Edward J. Harley, Edith A. Zang, Harvey J. Alter, Patricia E. Taylor, Anita DE Vera, George T. S. Chen, Aaron Kellner
Journal: New England Journal of Medicine (1982)

We evaluated the efficacy of hepatitis B vaccine (Heptavax-B) containing only the ad subtype in a randomized, placebo-controlled, double-blind trial among 865 staff members of 43 hemodialysis units in the United States. Surface antibody developed in 92.6 per cent of the subjects after two doses of vaccine and in 96 per cent after the six-month booster. The incidence of infections with hepatitis B virus (with or without hepatitis) was 9.9 per cent in placebo recipients and 2.2 per cent in vaccine recipients (P less than 0.01). The two cases of hepatitis B among vaccine recipients did not occur in subjects in whom antibody had developed. In 81 per cent of the hepatitis events, the virus was of the ay subtype. The indicence of ay virus was 8.2 per cent among placebo recipients and 1.2 per cent among vaccine recipients (P less than 0.005). We conclude that these data confirm the efficacy of the vaccine and demonstrate subtype cross-protection.
Abstract 843: Inhibition of AKT signaling promotes FOXO3a-dependent apoptosis in castration-resistant prostate cancer cells.
Authors: Trinath P. Das, Chendil Damodaran
Journal: Cancer Research (2013)

Abstract Treatment for aggressive prostate cancers involves hormonal ablation therapy, radical prostatectomy, radiation therapy, chemotherapy or in combination. Despite their initial sensitivity to these treatments, prostate cancer eventually progresses to castration -resistant prostate cancer (CRPC), which is both aggressive and refractory to current therapeutic modalities. Hence, CRPC demands the identification of novel targeted therapies with minimal side effects. We identified Withaferin-A (WA) a major bioactive compound derived from the medicinal plant, Withania somnifera, is extensively used in Asian herbal medicines to treat a variety of ailments, including cancer. Earlier, we reported that WA induced the pro-apoptotic gene, prostate apoptosis response-4 (Par-4) and apoptosis in CRPC cells. These results encouraged us to determine the mechanism of action of WA on CRPC cells. It is known that activated AKT negatively regulates forkhead transcription factor class O family protein (FOXO3a) that regulates genes involved with tumorigenesis, cell cycle arrest or apoptosis. In the present study, we found that FOXO3a is an upstream of Par-4 signaling which transactivates Par-4 function in CRPC cells. Inhibition of AKT activation by WA facilitates nuclear translocation of FOXO3a which in turn activates Par-4 mediated apoptosis in CRPC cells. Our confocal and immuno-precipitation studies confirmed that upon activation. FOXO3a and Par-4 were co-localized in the nucleus. Similar results were found with overexpression of FOXO3a showing transactivation of Par-4 and growth arrest in CRPC cells. Treatment of actinomycin-D or cyclohexmide along with WA, confirmed that FOXO3a regulation on Par-4 function in CRPC cells. On contrary, inhibition of FOXO3a by siRNA resulted in down regulation of Par-4 and apoptosis by WA in CRPC cells suggesting FOXO3a activation is necessary for the induction of Par-4 mediated apoptosis. Promoter bashing studies suggest a direct interaction of FOXO3a with Par-4 promoter; a sequential deletion of FOXO3a DNA binding sites in Par-4 promoter fails to induce Par-4 activation upon WA treatment in CRPC cells. Overall, our studies conclude that Par-4 is a target of FOXO3a, and Par-4 activation is required for induction of apoptosis in CRPC cells. Activation of FOXO3a is an attractive target for the treatment of CRPC and molecules such as WA can be explored further for the treatment of CRPC. Citation Format: Trinath P. Das, Chendil Damodaran. Inhibition of AKT signaling promotes FOXO3a-dependent apoptosis in castration-resistant prostate cancer 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 843. doi:10.1158/1538-7445.AM2013-843
Crossed Cerebellar Hypermetabolism Demonstrated by FDG PET
Authors: Ruixue Cui, Na Niu, Fang Li
Journal: Clinical Nuclear Medicine (2014)

Crossed cerebellar hypometabolism on 18F-FDG PET has been well described. However, crossed cerebellar hypermetabolism is rare. We described a case of crossed cerebellar hypermetabolism in a middle-aged woman. The patient underwent FDG PET to assess epileptogenic focus during her subclinical seizure episode, which was shown on video electroencephalography. The crossed cerebellar hypermetabolism was no longer visualized when her subclinical seizure was controlled.
Viable Tissue in an Area of Severely Reduced Perfusion Demonstrated With I-123 Iomazenil Brain SPECT Imaging of Benzodiazepine Receptors
Authors: K Hayashida, K Fukuchi, Y Hasegawa, N Kume, I H Cho, T Nishimura
Journal: Clinical Nuclear Medicine (1999)

A 70-year-old woman who experienced transient left hemiparesis had 90% stenosis of the right internal carotid artery. CT revealed small low-density areas in the subcortical frontal area. Baseline cerebral blood flow was reduced, and vasoreactivity was poor in the right frontoparietal area according to I-123 IMP brain SPECT with acetazolamide. The distribution of I-123 iomazenil was normal on the delayed SPECT image but reduced in the early SPECT image, mimicking baseline cerebral blood flow. The distribution of I-123 iomazenil SPECT on the delayed image reflected the normal binding potential of the benzodiazepine receptor and thus identified viable tissue in an area of severely reduced perfusion. These findings were confirmed by positron emission tomography.
Upper gastrointestinal tumors
Authors: D. O'Toole
Journal: Endoscopy (2011)

Improvements in both endoscopic detection methods and treatment techniques such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have been readily applied in the treatment of early gastric cancers (EGC), notably in Asia. The risk of lymph node metastases have been largely based on Japanese series. Proposed extended criteria for ESD in treating intestinal-type EGC include [2] [3]:1) differentiated mucosal cancer of any size without ulcer; 2) differentiated mucosal cancer ≤ 3 cm with ulcer; and 3) submucosal cancer ≤ 3 cm (sm1 < 500 µm), without lymphovascular invasion. This large retrospective Korean cohort described by Kang et al. included 478 patients who were naive to endoscopic therapies and who were undergoing gastrectomy and lymph node dissection for EGC (intramucosal 56 %, submucosal 44 %). Risk factors for lymph node invasion were analyzed and also compared with the extended criteria used for ESD of intestinal-type EGC. Similar to previous reports, the incidence of lymph node metastasis (13 %) was higher for submucosal EGCs than for mucosal EGCs (25 % vs. 3 %; P < 0.001), increased size (P < 0.001), depth of invasion (P < 0.001), and lymphovascular invasion (P < 0.001). In contrast to other reports, an elevated morphology (grouping Paris classification types I, IIa, IIa + IIb, IIa + IIc) was strongly associated with the risk for lymph node metastasis for the entire cohort (P < 0.001) and remained significant on multivariate analysis when restricted to intestinal-type lesions (n = 296) (P < 0.006). When the authors compared their results to the established extended criteria permitting ESD, seven patients with intestinal-type EGCs were found to have lymph node metastasis: 2 / 146 patients (1.4 %) with small (≤ 3 cm) non-ulcerated mucosal cancer; 2 / 126 patients (1.6 %) with cancer ≤ 3 cm with no lymphovascular emboli and irrespective of the presence of ulceration; and 3/20 patients (15.0 %) with intestinal-type submucosal cancer (sm1 ≤ 500 mm) without lymphovascular invasion and measuring ≤ 3 cm in size.
Abstract 1434: A mouse model of the most aggressive subgroup of human medulloblastoma
Authors: Daisuke Kawauchi, Giles Robinson, Tamar Uziel, Paul Gibson, Jerold Rehg, Cuilan Gao, David Finkelstein, Chunxu Qu, Stanley Pounds, David W. Ellison, Richard J. Gilbertson, Martine F. Roussel
Journal: Cancer Research (2012)

Abstract Human medulloblastomas are molecularly classified into four major subgroups. Among them, the MYC-subgroup, the most aggressive and the least curable is characterized by amplification or overexpression of the c-MYC gene. While mouse models for the human SHH-subgroup have advanced the development of targeted treatments for this subgroup, the absence of a preclinical model for the MYC-subgroup has severely limited our understanding of its biology and treatment. We have now generated the first mouse model of MYC-subgroup medulloblastoma that faithfully recapitulate the transcriptome, histopathology, and clinical behavior of the human disease. This mouse model was generated by orthotopic transplantation of percoll-purified Myc-transduced cerebellar cells from postnatal day 6-7 Trp53-deficient mice into the cortices or the cerebellum of immunocompromised recipient animals. While &amp;gt;2 x 105 cells from the mouse SHH-tumors are required to induce a tumor, 100 MYC-tumor cells were sufficient, suggesting that most MYC-tumor cells are tumor initiating cells. MYC-tumors can be passaged indefinitely as neurospheres that express markers associated with stem cells, including Prom1, Lgr5, Oct4, Nanog, and Sox2 and induce secondary medulloblastomas with similar characteristics as the primary tumors, after orthotopic transplant into the cortices of recipient mice. This novel medulloblastoma model should significantly advance our efforts to develop new therapeutic modalities and to determine the origin of this deadly childhood cancer. 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 1434. doi:1538-7445.AM2012-1434
Recommandations de la Société Française d'Endoscopie Digestive: Prothèses Biliaires
Authors: J. F. Rey, R. Dumas, J. M. Canard, T. Ponchon, D. Sautereau, T. Helbert, J. Escourrou, G. Gay, M. Giovannini, M. Greff, J. C. Grimaud, J. Lapuelle, B. Marchetti, B. Napoleon, L. Palazzo
Journal: Endoscopy (2002)

Since 1988, the Council of the French Society of Digestive Endoscopy has been publishing standards for good practice in endoscopy. These recommendations appear to us to be the best way of achieving better and more rational practice in medicine at present. Produced by a group of experts, and corrected by an even larger expert group, the guidelines are regularly updated in written form to help physicians in decision-making. Michel Greff, M.D., International Secretary, French Society of Digestive Endoscopy