tbuckley/cabot-search huggingface dataset:
P99 FXR stimulation with INT-747 in a rat biliary drainage model protects from hepatocellular injury after loss of enterohepatic circulation
Authors: R. G. J. Visschers, K. V. K. Koelfat, C. M. Hodin, R. Shiri-Sverdlov, W. A. Buurman, R. Mookerjee, K. Lenaerts, S. W. M. O. Damink
Journal: Gut (2011)

<h3>Introduction</h3> Enterocutaneous fistula are often associated with development of intestinal failure associated liver disease (IFALD), ultimately leading to liver damage. We hypothesise that this is caused by reduced farnosoid X receptor (FXR) stimulation, due to interruption of the enterohepatic circulation and consequent impact on bile acid synthesis. <h3>Aim</h3> We aimed at investigating the effect of specific stimulation of the farnosoid X receptor (FXR) with INT-747, a synthetic agonist, in a rat biliary diversion model. <h3>Methods</h3> Four groups of rats (n=6–8) were studied; two groups underwent bile duct cannulation and externalisation to achieve continuous biliary drainage, daily receiving either vehicle or INT-747 (Intercept Pharm LtD); two groups underwent laparotomy without cannulation also receiving either vehicle or INT-747. Loss of bile was recorded daily. After 7 days, plasma, serum and liver and intestinal tissue were collected. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), γ glutamyl transpeptidase (GGT) and total bilirubin were assessed, together with histological scoring of necrosis, inflammation, bile duct proliferation, fibrosis and steatosis. Expression of genes involved in the FXR pathway, and lipid and cholesterol metabolism were quantified by qPCR. <h3>Results</h3> Loss of bile was significantly reduced in the INT-747 group compared to the vehicle group. Serum levels of ASAT, ALAT, AP, GGT, bilirubin (total and direct) were all significantly increased in the bile drainage group when compared to controls (p&lt;0.05), suggesting hepatocellular damage. Interestingly, all parameters were significantly decreased in the bile drainage group receiving INT-747 (p&lt;0.05). Histological analyses showed normal liver histology in both sham groups. In contrast, large necrotic areas were observed in the biliary diversion group receiving vehicle with a high number of infiltrating inflammatory cells, which decreased significantly in the biliary diversion group receiving INT-747 (p&lt;0.05). Biliary diversion induced hepatic fibrosis and bile duct proliferation, which were both attenuated by INT-747 supplementation (p&lt;0.05). Although genes involved in the FXR pathway (FXR, SHP, CYP7A1 and CYP8B1) were influenced by bile drainage, no significant change was observed when rats received INT-747. <h3>Conclusion</h3> The present data demonstrate that stimulation of FXR with INT-747 can attenuate hepatocellular damage in an experimental model of IFALD. The results suggest a role of FXR in the development of hepatocellular damage, hepatic fibrosis and necrosis during biliary diversion. FXR stimulation has the potential to be a novel therapy for patients with IFALD.
Psychophysical scaling: Judgments of attributes or objects?
Authors: Gregory R. Lockhead
Journal: Behavioral and Brain Sciences (1992)

Abstract Psychophysical scaling models of the form R = f(I), with R the response and I some intensity of an attribute, all assume that people judge the amounts of an attribute. With simple biases excepted, most also assume that judgments are independent of space, time, and features of the situation other than the one being judged. Many data support these ideas: Magnitude estimations of brightness (R) increase with luminance (I). Nevertheless, I argue that the general model is wrong. The stabilized retinal image literature shows that nothing is seen if light does not change over time. The classification literature shows that dimensions often combine to produce emergent properties that cannot be described by the elements in the stimulus. These and other effects cannot be adjusted for by simply adding variables to the general model because some factors do not combine linearly. The proposed alternative is that people initially judge the entire stimulus – the object in terms of its environment. This agrees with the constancy literature that shows that objects and their attributes are identified through their relations to other aspects of the scene. That the environment determines judgments is masked in scaling studies where the standard procedure is to hold context constant. In a typical brightness study (where different lights are presented on the same background on different trials) the essential stimulus might be the intensity of the light or a difference between the light and the background. The two are perfectly confounded. This issue is examined in the case of audition. Judgments of the loudness of a tone depend on how much that tone differs from the previous tone in both pitch and loudness. To judge loudness (and other attributes) people first seem to process the stimulus object in terms of differences between it and other aspects in the situation; only then do they assess the feature of interest. Psychophysical judgments will therefore be better interpreted by theories of attention that are based in biology or psychology than those (following Fechner) that are based in classical physics.
SP0205 Igg4-Related Disease
Authors: J.H. Stone
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> IgG4-related disease (IgG4-RD) is a multi-organ fibroinflammatory condition that has now been described to affect essentially every organ system. Rheumatologists are frequently called upon to evaluate this disease because of its propensity to involve the salivary glands, orbits, lymph nodes, lungs, kidneys, aorta, and retroperitoneum. IgG4-RD often causes mass lesions and is therefore misdiagnosed frequently as a cancer, but it can also closely mimic common rheumatologic disorders such as Sjögren9s syndrome, systemic lupus erythematosus, and granulomatosis with polyangiitis (formerly Wegener9s), and large-vessel vasculitis. Both the diagnosis and treatment of IgG4-RD are challenging. This lecture will emphasize the multiple clinical features of IgG4-RD and its characteristic pathology findings, all in the context of treatment dilemmas. IgG4-RD is an immune-mediated condition that has lent itself well to therapeutic manipulations such as B cell depletion. Treatment efforts to date have yielded much knowledge about the nature of this disease and the larger immune system that drives IgG4-RD. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6350
Case 5-2006
Authors: David S. Walton, Shizuo Mukai, Eric F. Grabowski, John E. Munzenrider, Thaddeus P. Dryja
Journal: New England Journal of Medicine (2006)

An 11-year-old girl noticed a sudden loss of vision in her right eye. An examination disclosed leukokoria; she was sent to the emergency department. A test for visual acuity revealed only light perception in the right eye. Further examination and an ultrasonographic study disclosed a detached retina.
SATISFACCIÓN DE LOS PACIENTES TRAS COLONOSCOPIA AMBULANTE EN UN HOSPITAL TERCIARIO
Authors: A Huerta Madrigal, C González Asanza, B Merino Rodríguez, O Nogales Rincón, P Lastra Andrade, J Garrido Rodríguez, P Daza Toro, R Plá Mestre, E Cos Arregui, P Menchén Fernández Pacheco
Journal: Endoscopy (2010)

Objetivo: Conocer la satisfacción de los pacientes a los que se realizó una colonoscopia en nuestro centro y determinar los principales problemas de calidad percibida mediante un cuestionario.
Clinical and Nutritional Correlates of Survival in Breast Cancer.
Authors: C. Lis, D. Gupta, S. Dahlk, P. Vashi, C. Lammersfeld
Journal: Cancer Research (2009)

Abstract Background: Malnutrition can be a frequent manifestation of breast cancer and its treatment. Several nutritional assessment tools have varying levels of association with survival, and have been tested individually with different patient populations, sometimes making it difficult to assess the impact of one tool relative to the others. We therefore conducted a single-institution multivariate analysis of 3 most commonly used nutritional tools - Body Mass Index (BMI), Subjective Global Assessment (SGA) and bioimpedance-derived phase angle (PA).Material and Methods: A case series of 234 breast cancer patients treated at Cancer Treatment Centers of America. Using SGA, patients were classified as well nourished (SGA A), moderately malnourished (SGA B) or severely malnourished (SGA C). Cox proportional hazard models were used to evaluate the independent prognostic effects of SGA, PA and BMI after controlling for each other, stage at diagnosis and prior treatment history (newly diagnosed versus previously treated).Results: Of 234 patients, 74 were newly diagnosed while 160 had received prior treatment. 159 had early stage (I/II) disease at diagnosis, while 75 had late stage (III/IV). The median age at presentation was 52.8 years (range 25-75 years). The mean PA and BMI scores were 5.5 (std. dev = 1.1) and 28.7 (std. dev = 6.2) respectively. 171 patients were well-nourished (SGA A) while 63 were malnourished (SGA B/C). Multivariate Cox modeling, after adjusting for stage at diagnosis, prior treatment history and other nutritional variables, found that malnourished status (SGA B/C) was associated with a relative risk (RR) of 2.4 (95% CI: 1.5-3.9, p &amp;lt; 0.001). Late stage at diagnosis was associated with a RR of 2.0 (95% CI: 1.3-3.2; p = 0.003) and previously treated category was associated with a RR of 7.9 (95% CI: 3.9-15.8; p &amp;lt; 0.001). PA and BMI were found to be statistically non-significant.Discussion: We found that SGA A (well-nourished status) versus SGA B/C (moderate to severe malnourished status) identified patients with better survival outcomes independent of BMI, PA, stage at diagnosis and prior treatment history. Among the nutritional assessment tools evaluated, SGA emerged as the strongest predictor of survival in breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6048.
Abstract 3108: A novel role for hPygo2 in ribosomal RNA transcription.
Authors: Phillip G. P. Andrews, Kenneth R. Kao
Journal: Cancer Research (2013)

Abstract Background: Several ribosomes are required for each translated messenger RNA. During cell growth and division, a significant proportion of cellular resources are devoted to the production of ribosomes, but the epigenetic mechanisms by which cells adjust to this requirement are not fully understood. We have previously demonstrated that human Pygopus 2 (hPygo2) is highly expressed in, and required for the growth of a number of different cancers. hPygo2 functions as a chromatin remodeling protein through direct association with trimethylated Histone H3 at lysine4 (H3K4me3). It is here that hPygo2 likely serves as an adapter to which histone acetyltransferases can bind and promote further chromatin remodeling events required for transcription. We now present evidence that hPygo2 is involved in chromatin remodeling at the ribosomal (r)RNA promoter during proliferative growth of cancer cells. Methods: Immunoprecipitation (IP) and immunofluorescence (IF) was performed in breast (MCF7), ovarian (SKOV3) and cervical (HeLa) cancer cells. siRNAs were designed to specifically deplete hPygo2. For hPygo2 binding to the ribosomal gene promoter, chromatin IPs were used and analyzed by conventional or quantitative (q) PCR. 47S rRNA expression was measured by qPCR or by pulse-chase with either Br-UTP or 3H-uridine. Cell cycle analysis was performed by flow cytometry. Results: We found that hPygo2 interacted with UBF-1 and Treacle, two nucleolar proteins involved in 47S rRNA transcription. hPygo2 co-localized with UBF-1 and Treacle along with newly synthesized de novo rRNA in the nucleoli of cancer cells. hPygo2 was further detected at the ribosomal gene promoter along with core components of the rDNA transcription complex, including RNA polymerase I. Furthermore, hPygo2 was required for Histone H4 acetylation at the rRNA promoter and for transcription of the 47S pre-rRNA. Depletion of hPygo2 was accompanied by activation of the ribosomal stress response, detected by the binding of ribosomal protein L11 to hdm2, thereby inhibiting its E3 ubiquitin ligase activity resulting in p53 dependent growth arrest. Conclusion: Our results suggest that chromatin remodeling function of hPygo2 may serve to augment or maintain 47S pre-rRNA transcription required for ribosome biogenesis in cancer. Citation Format: Phillip G. P. Andrews, Kenneth R. Kao. A novel role for hPygo2 in ribosomal RNA transcription. [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 3108. doi:10.1158/1538-7445.AM2013-3108
Mutations in Sarcomere Protein Genes as a Cause of Dilated Cardiomyopathy
Authors: Mitsuhiro Kamisago, Sapna D. Sharma, Steven R. DePalma, Scott Solomon, Pankaj Sharma, Barbara McDonough, Leslie Smoot, Mary P. Mullen, Paul K. Woolf, E. Douglas Wigle, J.G. Seidman, John Jarcho, Lawrence R. Shapiro, Christine E. Seidman
Journal: New England Journal of Medicine (2000)

The molecular basis of idiopathic dilated cardiomyopathy, a primary myocardial disorder that results in reduced contractile function, is largely unknown. Some cases of familial dilated cardiomyopathy are caused by mutations in cardiac cytoskeletal proteins; this finding implicates defects in contractile-force transmission as one mechanism underlying this disorder. To elucidate this important cause of heart failure, we investigated other genetic causes of dilated cardiomyopathy.
PTH-133 Electronic Personal Health Records For Patients On Home Parenteral Nutrition: A Patient Satisfaction Survey
Authors: T Ambrose, R Topan, M Small, JM Nightingale, SM Gabe
Journal: Gut (2014)

<h3>Introduction</h3> The public demand for flexible access to health information and services is growing, encouraged by Intnet trends and policies promoting patient involvement. Patients Know Best® (PKB) is an electronic patient centred system providing a secure forum for patients to interact with healthcare teams. With increasing use of this system by our home parenteral nutrition patients we aimed to assess patient satisfaction with a survey. <h3>Methods</h3> PKB was introduced to patients during routine clinic visits and verbal consent obtained. We recorded the frequency of use, total number of electronic discussions held and the number of additional carers (other healthcare staff or family members) involved in their personal health record. We distributed a 10 question survey to all users. <h3>Results</h3> 119 patients (50 male, 69 female) were registered over a period of 18 months with a median age of 49 years (range 17–85 years, mean 48 years). A total of 5015 unique electronic conversations were recorded. These would usually have occurred via telephone. PKB has been used for 4 patients transitioning from paediatric to adult services and 2 patients from abroad. Other patients invited included 128 outside clinicians (eg local nutrition nurses and dietitians, transplant coordinators) and 29 carers. There were 58/119 (48.7%) responses including 1 incomplete dataset (61% female). 31/57 patients (54.4%) were over 50 years of age. 42/57 (73.7%) received parenteral nutrition and 13/57 (22.8%) fluids and electrolytes. 51/58 (87.9%) patients felt at least “somewhat confident” working online with their healthcare team and the same number felt that having access to the results was at least “somewhat helpful” – 32 (62.7%) of these responding “very/extremely helpful”. 30/58 (51.7%) use PKB a few times a month, 4/58 (6.9%) a few times a week and the remainder less frequently. The more useful features of PKB included Discussions (ie contacting the St Mark’s Nutrition team electronically) and Monitoring (ie test results). Patients use PKB to contact doctors/nutrition nurses more than dietitians/administrators. <h3>Conclusion</h3> Our survey suggests that our patient cohort find this a useful facility to contact us and improve the management of their long-term conditions. Not all patients access PKB regularly and they only had a short period in which to respond to the survey. This may explain the 49% response rate in an otherwise motivated patient population. This is an emerging and effective way for patients to interact with their healthcare teams and we have not found it has increased our workload. The ability to communicate seamlessly between different healthcare professionals reduces the current difficulties which exist when transferring information between multiple care providers (eg HIFNET). <h3>Disclosure of Interest</h3> None Declared.
SINUS NODE DYSFUNCTION IS ASSOCIATED WITH HIGHER LEFT ATRIAL PRESSURE DURING SINUS RHYTHM THAN ATRIAL FIBRILLATION IN PATIENTS WITH ATRIAL FIBRILLATION
Authors: Tae-Hoon Kim, Junbeom Park, Jin-Kyu Park, Jae-Sun Uhm, Boyoung Joung, Moon-Hyoung Lee, Hui-Nam Pak
Journal: Journal of the American College of Cardiology (2015)
Comparison of thromboembolism outcomes in gynecologic oncology patients in two urban hospitals
Authors: S. A. Wagner, R. Gogoi, A. Brusati, M. Liu, J. P. Curtin, B. Pothuri
Journal: Journal of Clinical Oncology (2008)

17562 Background: New York University (NYU), a private university hospital, and Bellevue Hospital (BH), a county hospital, provide services to two uniquely different patient populations. The primary objective of our study was to evaluate whether there was a difference in survival in gynecologic oncology patients (pts) with thromboembolism (TE) treated in the 2 different hospital systems. Methods: A retrospective chart review was performed identifying all pts with gynecologic malignancies and TE (deep venous thrombosis and/or pulmonary embolism) between 2002 and 2006 at the two institutions. Pts were excluded if they had a TE diagnosis more than one year prior to their cancer diagnosis, had thrombophilia or were on anticoagulation for other indications. Unpaired t-test, Chi square and log rank tests were utilized in the statistical analysis. Results: Twenty-four BH and 79 NYU pts were identified. A statistically significant difference in age (p=0.019) was noted with pts at BH presenting at a younger age (mean 55 vs 63 yrs). There was equal representation of Asian, Hispanic and Caucasian ethnicities at BH. However, a majority of pts at NYU were Caucasian (79% vs 30%). No statistically significant differences were noted between the two groups with respect to body mass index, smoking history, site and stage at presentation. Approximately 65% of pts in both hospitals received an IVC filter. Treatment with coumadin or lovenox was not found to be different between the two institutions. There was no significant difference in overall survival following a diagnosis of TE in gynecologic oncology pts treated at these two hospitals (p=0.0417). Conclusions: Despite age and ethnicity differences in pts treated at a private university hospital and a county hospital, no difference in overall survival was seen in gynecologic oncology pts diagnosed with TE. No significant financial relationships to disclose.
Abstract 3142: Hypermethylation of the tissue inhibitor of metalloproteinases-2 gene in multiple myeloma
Authors: Stefan Wilop, Edgar Jost, Claudia Schubert, James G. Herman, Tim H. Brümmendorf, Oliver Galm
Journal: Cancer Research (2012)

Abstract Multiple myeloma (MM) is a B-cell neoplasm that is characterized by the accumulation of malignant plasma cells in the bone marrow (BM) as well as abundant BM angiogenesis. Aberrant methylation of CpG islands near gene promoter regions is the most widely studied epigenetic abnormality in human malignancies and is associated with loss of gene function. There is increasing evidence for a role of the tissue inhibitor of metalloproteinases 2 (TIMP-2) gene as a tumor suppressor. Overexpression of TIMP-2 may result in decreased invasive potential, suppression of tumor growth and vascularization as well as inhibition of angiogenesis. We could previously show that TIMP-2 may become hypermethylated in association with transcriptional silencing in indolent and aggressive non-Hodgkin's lymphomas. Recently, downregulation of TIMP-2 was also reported in MM, and this is thought to contribute to increased BM angiogenesis. In this study, we determined the methylation status of the promoter-associated CpG island of TIMP-2 in primary MM samples and investigated correlations between TIMP-2 methylation and clinical parameters. Methylation of the promoter-associated CpG island of TIMP-2 was analyzed by methylation-specific polymerase chain reaction (MSP) in samples from 84 MM patients (median age 65 years [range 40-94]; 48 males, 36 females; 79 BM samples, 5 peripheral blood samples). Overall survival curves were plotted according to the method of Kaplan and Meier and compared using the log-rank test. Correlations between variables were analyzed using the Fisher's exact two-sided test and independent t-test, respectively. MSP analysis revealed aberrant methylation of the TIMP-2 promoter region in 4/84 MM patient samples. We found an association of TIMP-2 hypermethylation with plasma cell leukemia (p&amp;lt;0.0001) and decreased platelet counts (111 G/l vs. 258 G/l; p=0.04). There was a trend towards an inferior overall survival in MM patients with a hypermethylated TIMP-2 gene, but this difference was not statistically significant (p=0.09). We conclude that promoter hypermethylation of TIMP-2 is a novel epigenetic event in MM that may contribute to disease progression and could serve as a prognostic biomarker. Further studies are warranted to elucidate the functional consequences of epigenetic dysregulation of TIMP-2 in the pathogenesis of MM. Additionally, the increasing evidence for the role of DNA methylation changes in MM may serve as a basis for the use of epigenetically targeted therapeutic approaches in malignant plasma cell disorders. 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 3142. doi:1538-7445.AM2012-3142
Cerebral Infarction Due to Traumatic Internal Carotid Artery Dissection
Authors: J. BREMERICH, EBERHARD KIRSCH, J. MÜLLER-BRAND
Journal: Clinical Nuclear Medicine (1997)

The authors report a case of a 39-year-old man who had a skiing accident. The following day he continued to ski, but later, while driving home, he lost consciousness and caused an accident. On hospital admission, he had a left hemiparesis. Traumatic dissection of the internal carotid artery with subsequent infarction in the right middle cerebral artery was diagnosed. Treatment with heparin resulted in the almost complete resolution of neurologic deficits.
Serologic and Immunohistochemical Study of Human and Experimental Thyroiditis
Authors: David D. Porter, Robert H. Fennell
Journal: New England Journal of Medicine (1961)

INTEREST in autoimmunity as a factor in the pathogenesis of disease has been stimulated by observations on thyroiditis. Thyroiditis has been produced experimentally in rabbits, guinea pigs and dogs by injection of rabbit thyroid extract,1 , 2 and circulating antibodies have been demonstrated in patients with Hashimoto's thyroiditis.3 Discovery of circulating antithyroid antibodies in patients with myxedema has suggested an autoimmune mechanism in the pathogenesis of such thyroid deficiency.4 Passive transfer of antithyroid antibodies from the mother to the fetus, with resultant damage to the fetal thyroid gland, has been postulated as an explanation for some cases of cretinism.5 , 6 However, circulating antithyroid . . .