tbuckley/cabot-search huggingface dataset:
PWE-058 Tissue Acquisition from Solid Pancreatic Lesions – Endoscopy or Surgery
Authors: M Nayar, D Tai Kung, B Haugk, S White, D Manas, B Jaques, G Sen, J French, R Charnley, K Oppong
Journal: Gut (2013)

<h3>Introduction</h3> The accurate diagnosis of solid pancreatic masses is important in directing appropriate management of patients. The methods commonly used are percutaneous, laparoscopic and EUS guided biopsy of these lesions. Laparoscopic guided biopsy consumes theatre time and space and can be more expensive than the alternatives. In our unit; laparoscopic guided biopsy is reserved for patients who have an inconclusive result from an EUS guided biopsy or are considered for trial resection. The aim of this study was to look at the diagnostic performance of endoscopic ultrasound (EUS) guided biopsy (fine needle aspiration (FNA) or pro-core biopsy) and laparoscopic (lap) guided biopsy of solid pancreatic masses in a large HPB referral centre. <h3>Methods</h3> Retrospective review of patients undergoing EUS or laparoscopic guided biopsy for solid lesions between January 2011 and March 2012. Data was obtained from a dedicated prospectively maintained database in the histopathology department. Final diagnosis was based on positive histology/cytology of pancreatic adenocarcinoma. Benign cases were followed up for a period of at least six months. <h3>Results</h3> 464 specimens from the pancreas (histology + cytology including pancreatic resections) were received by the histopathology department during this period. Of these 275/464 (59%) patients had tissue biopsy of solid lesions. These included: EUS guided biopsy = 253 and Laparoscopic guided biopsy = 22. In the latter group; 10/22(45%) had a previous EUS of which 8/10 had an accurate diagnosis. 12/22(54%) patients went straight for laparoscopic guided biopsy. For the purposes of this study; highly suspicious and malignant samples were categorised as malignant. The accuracy, sensitivity and negative predictive value for EUS guided biopsy and laparoscopic guided biopsy were 92%/96%; 90%/94% and 74%/89% respectively. The inadequate aspirate rate was 5% and 0% respectively. There was no significant difference between the two groups. The cost of performing these procedures in our trust were: EUS guided biopsy £1094 and lap guided biopsy £ 2164. <h3>Conclusion</h3> In our unit;EUS guided biopsy of solid pancreaticobiliary lesions provides high diagnostic accuracy with a low inadequate aspirate rate. Our data supports the role of EUS guided FNA as the first modality of tissue acquisition from the pancreas. Though this data also shows the cost effectiveness of EUS guided biopsy over lap guide biopsy; in units with lower diagnostic accuracy of EUS guided biopsy the cost benefit may not be realised. <h3>Disclosure of Interest</h3> None Declared.
Effect of ulcer healing on the prognosis of chronic gastric ulcer: Four-year follow-up
Authors: D. W. Piper, J. Shinners, M. Greig, J. Thomas, S. L. Waller
Journal: Gut (1978)

Eighty three patients were followed-up for four years after an admission to hospital with a chronic gastric ulcer proven by radiology (index ulcer). The index ulcer healed completely in 50 patients, but was unhealed at the time of discharge in the other 33. Significantly fewer patients whose index ulcer was healed compared with those whose ulcer was unhealed at discharge had had a recurrence by one (p &lt; 0·05), two, three and four years9 (p &lt; 0·01) follow-up. Moreover, the rate of recurrence was significantly greater for those patients with unhealed, compared with those with a healed index ulcer (p &lt; 0·05) and by the end of the four-year period 61% of patients with unhealed, compared with 26% of those with healed index ulcers had had a recurrence. Patients over the age of 60 years with unhealed index ulcers had a significantly poorer prognosis than those of similar age whose index ulcer was healed at discharge (p &lt; 0·025). The sex of the ulcer patient did not significantly influence ulcer recurrence. Large ulcers (&gt; 57 mm<sup>2</sup>) were less often healed on initial discharge and were more frequently associated with recurrence at one (p &lt; 0·05), two (p &lt; 0·025), three and four years (p &lt; 0·01) than smaller ulcers ([unk]57 mm<sup>2</sup>). Heavy intake of analgesics adversely influenced the course of patients whose ulcer was unhealed (p &lt; 0·05), but did not alter the recurrence rate in those whose ulcer was healed. Ulcer recurrence was not influenced by smoking habits or by alcohol consumption.
Peginterferon alfa-2a for hepatitis C after liver transplantation: Two randomized, controlled trials
Authors: Naga Chalasani, Cosme Manzarbeitia, Peter Ferenci, Wolfgang Vogel, Robert J. Fontana, Michael Voigt, Caroline Riely, Paul Martin, Lewis Teperman, James Jiao, Juan Carlos Lopez‐Talavera
Journal: Hepatology (2005)

There is currently no effective treatment for recurrent hepatitis C after orthotopic liver transplantation (OLT). We therefore performed two randomized, controlled trials--a prophylaxis trial and a treatment trial--to evaluate the safety and efficacy of peginterferon alfa-2a in patients who had undergone OLT. The prophylaxis trial enrolled 54 patients within 3 weeks after OLT, and the treatment trial enrolled 67 patients 6 to 60 months after OLT. In each trial, patients were randomized to treatment with once weekly injections of 180 microg peginterferon alfa-2a or no antiviral treatment for 48 weeks and were followed up for 24 weeks thereafter. Peginterferon alfa-2a treated patients had significantly lower hepatitis C virus RNA levels and more favorable changes in hepatic histological features compared with untreated controls. However, only 2 treated patients in the prophylaxis trial (8%) and 3 in the treatment trial (12%) achieved a sustained virological response. In the prophylaxis trial, 8 patients (31%) in the peginterferon alfa-2a group and 9 (32%) in the untreated group were withdrawn prematurely; whereas in the treatment trial, 10 patients (30%) in the peginterferon alfa-2a group and 6 (19%) in the untreated group were withdrawn prematurely. The incidence of acute rejection was similar in the treated and untreated groups in both the prophylaxis (12% vs. 21%; P = .5) and treatment (12% vs. 0%; P = .1) trials. In conclusion, peginterferon alfa-2a treatment for 48 weeks is safe and tolerable and offers some efficacy in the post-OLT setting. Randomized controlled studies are needed to establish the efficacy of pegylated interferon and ribavirin in patients who have undergone OLT.
598 The IL6 high producer (HP) genotype (IL6 +174G/G, and +174G/C) is associated with treatment-induced recovery from acute hepatitis C infection in HIV-infected patients
Authors: J. Nattermann, M. Vogel, G. Ahlenstiel, M. Schulz, T. Sauerbruch, J.K. Rockstroh, U. Spengler
Journal: Journal of Hepatology (2006)
Hepatitis B virus genomes of patients with fulminant hepatitis do not share a specific mutation
Authors: M Sterneck, S Gunther, T Santantonio, L Fischer, C E Broelsch, H Greten, H Will
Journal: Hepatology (1996)

The pathogenesis of fulminant hepatitis B virus (HBV) infection is not well understood. The aim of this study was to investigate whether there is an association between specific viral variants and a fulminant disease course. The entire HBV genomes from the serum of eight patients with fulminant HBV infection and one patient with fulminant hepatitis during reinfection after liver transplantation were investigated. After isolation and amplification of viral DNA by polymerase chain reaction (PCR), plus and minus strands were directly sequenced. Sequence data were analyzed by comparative sequence alignments with 35 and 2 complete HBV genome sequences from patients without and with fulminant hepatitis, respectively. Several point mutations were present in all regions of the genomes. Many nucleotide changes had never or rarely been found in the reported HBV isolates from patients without fulminant hepatitis. A distinct mutation present in all genomes was not identified. Clusters of rare and unique mutations were observed in the enhancer II core promoter region. Mutations previously suggested to be associated with fulminant HBV infection were not consistently found. A precore stop codon mutation at nucleotide position 1896 or an A-to-T mutation at nucleotide position 1762 and a G-to-A mutation at nucleotide position 1764 in the core promoter region were present in four and three cases, respectively. Fulminant HBV infection does not appear to be caused by a specific genomic mutation. However, various mutations clustering in the enhancer II core promoter region may contribute to a fulminant disease course.
Eating, Loving and Dying: A Psychology of Appetites
Authors: Marshall F. Gilula
Journal: JAMA (1974)

Physicians who truly understand obesity will find Daniel Cappon's pithy monograph conservative, well written, and accurate, but narrow in scope. The author's chief point is that overweight is caused by a combination of overeating and insufficient exercise. Although the thesis is hardly original, it can be scathingly effective when applied. Dr. Cappon's psychoanalytic background and extensive experience in treating both obesity and cachexia make for an interesting and well-crafted approach to a familiar problem. One current research trend is to lump total drug and food abuse into the category of<i>substance abuse</i>. This concept can give the physician options of perceiving important similarities between obesity, alcoholism, and heroin addiction. All forms of substance abuse have in common two features: (1) an imbalance in the metabolism or utilization of the substance, and (2) lack of proper exercise and mind-body balance that choice forms of corrective exercise may help to induce. <i>Eating,</i>
Imaging T-tubules: dynamic membrane structures for deep functions
Authors: Tobias Kohl, Stephan E. Lehnart
Journal: Cardiovascular Research (2013)

This editorial refers to ‘Emerging mechanisms of T-tubule remodelling in heart failure’ by A. Guo et al ., pp. 204–215, this issue and ‘Ultrastructural uncoupling between T-tubules and sarcoplasmic reticulum in human heart failure’ by H.-B. Zhang, et al ., pp. 269–276, this issue. 

Extensive intracellular contacts of the endo/sarcoplasmic reticulum (ER/SR) with transverse tubules (TTs) are fundamental for intracellular Ca2+ cycling in cardiac muscle. For this, TTs extend from the cytoplasmic surface deep into the cell, setting up a complex three-dimensional (3D) membrane network, referred to as ‘transverse axial tubular system’ (TATS) ( Figure 1 A ). The TATS extends over several orders of magnitude in size, e.g. from local TT diameters <100 nm to cell-wide continuous networks expanding over 100 μm, in order to provide thousands of subcellular TT contacts with the ER organelle via junctional SR (jSR) contacts in a typical ventricular myocyte (VM). Not surprisingly, approaches to study the TT membrane structures and properties of the TATS network encompass different imaging and physiological methods. However, until recently ultrastructural TT resolution vs. continuous representation of TATS regions had to be traded against each other. Just imagine representative EM studies (smallest field of view, possible resolution ≤1 nm) when compared with confocal fluorescence microscopy of histological samples (field of view of ∼150 × 150 µm at ∼250 nm resolution using ×63 objectives). Meanwhile this methodological gap is addressed by recent super-resolution fluorescence microscopy approaches (see below).1 Despite apparent gaps between imaging resolution and the nanometric nature of subcellular membrane compartments, conventional fluorescence microscopy is essential to characterize TATS membranes in living samples. In particular, functional imaging studies of isolated cells and two-photon imaging of intact heart tissue have related typical TATS architectures to subcellular functions like Ca2+ release events (sparks) in resting cells (for diastole) or Ca2+ transients …
Health in Africa: International experience may provoke animosity towards those returning home
Authors: Andrew C Don-Wauchope
Journal: BMJ (2005)

Adjuvant trastuzumab for breast cancer Assessing HER2/neu status incurs more costs for treatmentEditor-The results of recent trials are likely to continue to fuel the demand for trastuzumab in the adjuvant setting of early breast cancer, 1 as well as a possible neoadjuvant treatment in the near future.However, Dent and Clemons did not discuss the difficulty in obtaining accurate and reproducible assessment of HER2/neu gene overexpression.Immunohistochemical testing measures HER2/neu protein expression whereas in situ hybridisation measures gene amplification.Patients with equivocal immunohistochemical results require in situ hybridisation to determine definitive status because interobserver variability using immunohistochemical testing is appreciable.At least 20% of patients with positive immunohistochemical results will be truly negative for HER2/neu gene amplification; these patients would not benefit from trastuzumab. 2 These difficulties in assessing HER2/ neu status have been encountered in studies testing trastuzumab, and in situ hybridisation testing has been used as the gold standard. 3 As the clinical utility of trastuzumab widens guidelines on HER2/neu testing must be clear to ensure appropriate use of trastuzumab.Clearly this testing will incur additional costs to trastuzumab treatment.
522. Enhanced Repair of Articular Cartilage Defects in Rabbits by Overexpression of Human FGF-2 Via rAAV-Mediated Gene Transfer
Authors: Magali Cucchiarini, Henning Madry, Chunyan Ma, Tanja Thurn, David Zurakowski, Dieter Kohn, Michael D. Menger, Stephen B. Trippel, Ernest F. Terwilliger
Journal: Molecular Therapy (2005)
A novel Rag2−/−γc−/−-xenograft model of human CLL
Authors: Maria Teresa Sabrina Bertilaccio, Cristina Scielzo, Giorgia Simonetti, Maurilio Ponzoni, Benedetta Apollonio, Claudia Fazi, Lydia Scarfò, Martina Rocchi, Marta Muzio, Federico Caligaris-Cappio, Paolo Ghia
Journal: Blood (2009)
Abstract 1020: Trefoil factor 3 promotes angiogenesis in mammary carcinoma
Authors: Wai-Hoe Lau, Vijay Pandey, Xiangjun Kong, Arindam Banerjee, Tao Zhu, Peter E. Lobie
Journal: Cancer Research (2014)

Abstract Mammary carcinoma cells produce various growth factors that stimulate endothelial cells to promote angiogenesis in mammary carcinoma. Trefoil Factor 3 (TFF3) is a small secreted protein which is involved in protection of the gastrointestinal tract against mucosal damage. Our laboratory has also previously identified TFF3 as an orthotopically expressed oncogene in mammary carcinoma and observed that TFF3 stimulated oncogenicity and invasiveness of mammary carcinoma cells. Several studies have reported a significant positive association between TFF3 protein expression and microvessel density. However, the potential functional role of TFF3 in mammary carcinoma angiogenesis has not been determined. Herein, we defined the functional effect of TFF3 secreted by mammary carcinoma cells on the behavior of endothelial cells in de novo tumor angiogenesis. We utilized MCF-7 and T47D cells as our in vitro models by stable forced expression of TFF3 or siRNA mediated depletion of TFF3 in these cell lines. The effect of TFF3 secreted from mammary carcinoma cells on human umbilical vein endothelial cells (HUVEC) was determined by using a co-culture transwell system, whereby HUVEC cells were co-cultured with mammary carcinoma cells. We demonstrated that TFF3 secreted from mammary carcinoma cells promoted HUVEC cells monolayer cell cycle progression and proliferation, survival, migration, invasion, and in vitro tubule formation. In a xenograft model, mammary carcinoma cells with forced expression of TFF3 produced tumors with increased microvessel density (CD31 and CD34) compared to tumors formed by control cells. Depletion of TFF3 in mammary carcinoma cells by siRNA or inhibition with anti-TFF3 polyclonal antibody significantly decreased HUVEC cells monolayer cell cycle progression and proliferation, migration, invasion, and in vitro tubule formation. Mechanistically, we observed that TFF3 increased IL-8 expression in mammary carcinoma cells with forced expression of TFF3. Depletion of IL-8 in mammary carcinoma cells by siRNA or inhibition with anti-IL8 monoclonal antibody significantly decreased migration, invasion, and in vitro tubule formation of HUVEC cells promoted by TFF3. Hence, TFF3 is a promoter of tumor angiogenesis, which may co-coordinate with the growth promoting and metastatic actions of TFF3 in mammary carcinoma to enhance tumor progression. Citation Format: Wai-Hoe Lau, Vijay Pandey, Xiangjun Kong, Arindam Banerjee, Tao Zhu, Peter E. Lobie. Trefoil factor 3 promotes angiogenesis in mammary carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1020. doi:10.1158/1538-7445.AM2014-1020
ERBB2 Inhibition and Heart Failure
Authors: Gregory M. Cote, Douglas B. Sawyer, Bruce A. Chabner
Journal: New England Journal of Medicine (2012)

The anti-ERBB2 antibody, trastuzumab, was developed to treat ERBB2-positive breast cancer. The cardiac toxicity it produced was unexpected but led to new insights about a role for ERBB2 in the response of the heart to stress.
Driving with Sleep Apnea
Authors: Paul M. Suratt, Larry J. Findley
Journal: New England Journal of Medicine (1999)

Snoring used to be a laughing matter. We now know that it can be a sign of obstructive sleep apnea, a serious condition characterized by repeated collapse of the pharynx during sleep, leading to periods in which breathing stops (apnea) or hypoventilation occurs (hypopnea). These episodes are usually terminated by brief periods of arousal,1 which disturb sleep and lead to excessive daytime sleepiness. People with sleep apnea are typically obese, have loud, irregular snoring, and have hypersomnia or fatigue during the day. Many people do not have all these characteristics, and the condition is most reliably diagnosed by overnight polysomnography . . .
AN EPIDEMIC DIARRHEAL DISEASE OF SUCKLING MICE
Authors: Alwin M. Pappenheimer, John F. Enders
Journal: The Journal of Experimental Medicine (1947)

Intranuclear inclusions were found in 75 per cent of young mice suffering from a spontaneous diarrheal disease. They were confined to the epithelial cells of the small intestine, and to the intestinal and mesenteric lymphadenoid tissue. They were seen only between the 10th and 15th days after birth, in apparently healthy control mice of the same age group, they were found in only two of thirty-six animals (5.5 per cent) and these were in mice from the same room and stock as the diseased animals. Nursing mice experimentally infected by feeding unfiltered diarrheal feces, also showed inclusion bodies from the 10th to the 14th day inclusive. The inclusions were not present during a corresponding age period, in the healthy stock used for these experiments. Inclusions have also been found in the cytoplasm of the intestinal epithelial cells of young mice but without any significant relation to the disease under study. No conclusions as to their nature are warranted at this time.
Intracapillary leucocyte accumulation as a novel antihaemorrhagic mechanism in acute pancreatitis in mice
Authors: E Ryschich, V Kerkadze, O Deduchovas, O Salnikova, A Parseliunas, A Marten, W Hartwig, M Sperandio, J Schmidt
Journal: Gut (2009)

Pancreatic infiltration by leucocytes represents a hallmark in acute pancreatitis. Although leucocytes play an active role in the pathophysiology of this disease, the relation between leucocyte activation, microvascular injury and haemorrhage has not been adequately addressed.We investigated intrapancreatic leucocyte migration, leucocyte extravasation and pancreatic microperfusion in different models of oedematous and necrotising acute pancreatitis in lys-EGFP-ki mice using fluorescent imaging and time-lapse intravital microscopy.In contrast to the current paradigm of leucocyte recruitment, the initial event of leucocyte activation in acute pancreatitis was represented through a dose- and time-dependent occlusion of pancreatic capillaries by intraluminally migrating leucocytes. Intracapillary leucocyte accumulation (ILA) resulted in dense filling of almost all capillaries close to the area of inflammation and preceded transvenular leucocyte extravasation. ILA was also initiated by isolated exposure of the pancreas to interleukin 8 or fMLP, demonstrating the causal role of chemotactic stimuli in the induction of ILA. The onset of intracapillary leucocyte accumulation was strongly inhibited in LFA-1(-/-) and ICAM-1(-/-) mice, but not in Mac-1(-/-) mice. Moreover, prevention of intracapillary leucocyte accumulation led to the development of massive capillary haemorrhages and transformed mild pancreatitis into lethal haemorrhagic disease.ILA represents a novel protective and potentially lifesaving mechanism of haemostasis in acute pancreatitis. This process depends on expression of LFA-1 and ICAM-1 and precedes the classical steps of the leucocyte recruitment cascade.
125 DESPITE PERSISTENT HIGH PLASMA LEVELS PEGYLATED INTERFERON-ALPHA ONLY TRANSIENTLY INDUCES INTERFERON STIMULATED GENES IN THE LIVER OF PATIENTS WITH CHRONIC HEPATITIS C
Authors: M.T. Dill, Z. Makowska, J.E. Vogt, M. Filipowicz, L. Terracciano, V. Roth, M.H. Heim
Journal: Journal of Hepatology (2012)
Propofol versus Midazolam Regarding Their Antioxidant Activities
Authors: MASAHIKO TSUCHIYA, AKIRA ASADA, KEIKO MAEDA, YASUYO UEDA, EISUKE F. SATO, MITSUO SHINDO, MASAYASU INOUE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Propofol and midazolam are commonly used as sedatives for critically ill patients. These patients usually suffer from the pathologic effects of oxidative stress, predominantly caused by an imbalance between the generation of reactive oxygen species and the antioxidant defense system. Therefore, the antioxidant activities of propofol and midazolam may be of clinical importance. We investigated the activities of these two sedatives against hydrophilic or lipophilic peroxyl radicals in a homogeneous solution and in the presence of erythrocyte membranes. A chemical analysis of the homogeneous solution revealed that propofol efficiently scavenged hydrophilic peroxyl radicals (50% inhibitory concentration [IC50] = 1.3 × 10− 4 M), whereas midazolam efficiently scavenged lipophilic radicals (IC50 = 1.5 × 10− 5 M). Further, in membrane systems, propofol inhibited the oxidative damage induced by either hydrophilic or lipophilic radicals (IC50 = 1.5 × 10− 5 M for hydrophilic radicals and IC50 = 3.0 × 10− 4 M for lipophilic radicals), whereas midazolam did very little. In previous studies, we demonstrated that antioxidant activity is highly affected by the location and properties of the reaction site. The discrepancy in antioxidant activity between a homogeneous condition and in the presence of membranes can be well explained by this concept, and again emphasizes the importance of membranes in determining antioxidant activity. To further understand the biologic significance of these antioxidant properties, the effect of the two agents on endothelium-dependent relaxation was studied. Application of oxidative stress to aortic rings by treating them with peroxyl radicals led to a significant blockade of acetylcholine-induced relaxation after submaximal contraction with phenylephrine. Propofol pretreatment greatly attenuated the impairment in comparison with midazolam, which agrees with the concept of antioxidant activity in the presence of membranes. The results of the present study suggest that propofol has a greater potential to reduce oxidative stress than midazolam.