tbuckley/cabot-search huggingface dataset:
PTU-198 Towards objective endoscopic diagnosis of early Barrett's neoplasia using fibre-optic Raman spectroscopy
Authors: M Almond, J Hutchings, C Kendall, N Stone, N Shepherd, H Barr
Journal: Gut (2012)

<h3>Introduction</h3> Raman spectroscopy is a powerful analytical technique that can rapidly and accurately identify biochemical changes in cells that have become neoplastic. We are aiming to translate this laboratory technique into an endoscopic tool that can identify high-grade dysplasia (HGD) and early malignant change (T1a, T1sm1) within Barrett9s oesophagus. Here we aim to demonstrate that a novel fibre-optic Raman probe can correctly classify the pathology of ex vivo oesophageal tissue. <h3>Methods</h3> A custom-built Raman probe, designed to fit through the instrument channel of a standard endoscope, was used to measure Raman spectra from ex vivo oesophageal tissue following oesophagectomy, endoscopic resection, or point biopsy from patients with Barrett9s oesophagus +/- neoplasia. 1s spectra were measured using a monochromatic 830 nm laser for excitation. Multivariate analysis was used to correlate Raman spectra with histopathological diagnosis and calculate probe accuracy. <h3>Results</h3> 348 spectra were measured from ex vivo tissue from 28 patients. Fibre-optic Raman measurements were able to discriminate between HGD/adenocarcinoma and non-dysplastic Barrett9s oesophagus (BO) with a sensitivity of 91% and specificity of 96%. <h3>Conclusion</h3> Fibre-optic Raman Spectroscopy could enable endoscopic targeting of early neoplastic lesions in the oesophagus facilitating potentially curative endoscopic resection. Preparation is underway for an in vivo pilot study. <h3>Competing interests</h3> None declared.
Abstract B85: High malignant prostate cancer cells developed enhanced tumor-initiating/metastatasis-initiating activity and altered the lung microenvironment
Authors: Sheue-Fen Tzeng, Chin-Hsien Tsai, Ming-Shyue Lee, Pei-Wen Hsiao
Journal: Cancer Research (2015)

Abstract Hormone-refractory and metastatic prostate cancer (PCa) both result in therapeutic failure. Developing PCa animal model is critical to understand the cancer progression and to access therapeutic effects. Here, we established the orthotopic xenograft of androgen-independent PCa cell line, 22Rv1, in nude mouse model and cultured the metastatic cancer cells. The same procedure was repeated to evolve highly metastatic cells, 22Rv1-LN3. In experimental metastasis, 22Rv1-LN3 can colonize and grow in the LN, lung and brain through tail vein injection but 22Rv1 cell failed to colonize in these organs. Besides, intracardiac injection of 22Rv1-LN3 also caused bone metastasis. In the model, we found 22Rv1-LN3 cell have higher protease activity (e.g. matriptase and MMP9) along with lower level of protease inhibitors, (e.g. HAI-2, a matriptase inhibitor and TIMP2/TIMP3). Transcriptional level of these genes determined the in vitro invasion activity and in vivo tumorigenicity. Given the differential capacity to seed different tissues, we further analyze the stem cell property by tumorsphere assay and in vivo transplantation with a reduced cell number. Sphere-formation rate in 22Rv1-LN3 cells was 8% compared to only 0.1% in 22Rv1 cells. Tumorigenicity of 22Rv1-LN3 cells in orthotopic transplantation was 100% (8/8) compared to 20% (2/10) in 22Rv1 cells. Moreover, primary tumor of 22Rv1-LN3 cells developed spontaneous metastases in lymph nodes and lung at 8-week, whereas 22Rv1 cells hardly metastasized even at 14-week. As analyzed by qRT-PCR, primary 22Rv1-LN3 tumor vs. 22Rv1-Luc2 induced higher levels of Arginase and iNOS expression in lung tissue, which indicates the proclivity for metastatic niche formation. In conclusion, this PCa progression model not only elevated the malignant properties of cancer cells but also influenced the tumor microenvironment. Citation Format: Sheue-Fen Tzeng, Chin-Hsien Tsai, Ming-Shyue Lee, Pei-Wen Hsiao. High malignant prostate cancer cells developed enhanced tumor-initiating/metastatasis-initiating activity and altered the lung microenvironment. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B85. doi:10.1158/1538-7445.CHTME14-B85
An antiapoptotic role of sorting nexin 7 is required for liver development in zebrafish
Authors: Liangliang Xu, Wenguang Yin, Jianhong Xia, Meixiu Peng, Song Li, Shuo Lin, Duanqing Pei, Xiaodong Shu
Journal: Hepatology (2011)

Sorting nexin (SNX) family proteins are best characterized for their abilities to regulate protein trafficking during processes such as endocytosis of membrane receptors, endosomal sorting, and protein degradation, but their in vivo functions remain largely unknown. We started to investigate the biological functions of SNXs using the zebrafish model. In this study, we demonstrated that SNX7 was essential for embryonic liver development. Hepatoblasts were specified normally, and the proliferation of these cells was not affected when SNX7 was knocked down by gene-specific morpholinos; however, they underwent massive apoptosis during the early budding stage. SNX7 mainly regulated the survival of cells in the embryonic liver and did not affect the viability of cells in other endoderm-derived organs. We further demonstrated that down-regulation of SNX7 by short interfering RNAs induced apoptosis in cell culture. At the molecular level, the cellular FLICE-like inhibitory protein (c-FLIP)/caspase 8 pathway was activated when SNX7 was down-regulated. Furthermore, overexpression of c-FLIP(S) was able to rescue the SNX7 knockdown-induced liver defect.SNX7 is a liver-enriched antiapoptotic protein that is indispensable for the survival of hepatoblasts during zebrafish early embryogenesis.
Lymphoblastoid interferon alfa-n1 improves the long-term response to a 6-month course of treatment in chronic hepatitis C compared with recombinant interferon alfa-2b: Results of an international randomized controlled trial
Authors: Geoffrey C. Farrell, Bruce R. Bacon, Robert D. Goldin
Journal: Hepatology (1998)

The aim of this study was to compare the short-term and long-term efficacy and safety of lymphoblastoid interferon with a recombinant interferon alfa (IFN-α) in a 24-week treatment course for chronic hepatitis C. One thousand seventy-one patients with chronic hepatitis C were randomized to receive lymphoblastoid IFN-αn1 or recombinant IFN-α2b at the same dosing regimen, 3 million units administered subcutaneously three times a week for 24 weeks. Hepatitis C viral (HCV) genotype (by line probe assay) was determined at baseline, and serum HCV RNA level (by quantitative reverse-transcriptase polymerase chain reaction) was measured at baseline and weeks 24, 48, and 72. Primary end points were normalization of serum alanine aminotransferase (ALT) levels at end of therapy (week 24) and sustained ALT normalization at weeks 48 and 72. Secondary end points were nondetectability of serum HCV RNA at 24, 48, and 72 weeks, and histological improvement at weeks 24 and 72. The two treatment groups were similar with respect to demographic, clinical, and histological variables (10% had cirrhosis at entry), baseline serum HCV RNA levels, and distribution of HCV genotypes. Intent-to-treat analysis showed that ALT response at end of treatment was 35.3% for IFN-αn1 and 37.9% for IFN-α2b ( P = .38). Histological improvement and nondetectability of HCV RNA were also similar between the two treatment groups at the end of treatment, as were the type and frequency of reported adverse experiences. Among treatment responders, post-treatment relapse was significantly less frequent with IFN-αn1 than with IFN-α2b. Thus, sustained ALT responses (SR) to IFN-αn1 were significantly more frequent than SR to IFN-α2b (12.0% vs. 7.6% at 48 weeks, P = .02; 10.3% vs. 6.7% at 72 weeks, P equals; .04). SR were associated with viral loss and histological improvement, and more patients treated with IFN-αn1 were HCV RNA negative at week 72 compared with patients treated with IFN-α2b ( P = .03). SR at week 72 were two- to sixfold better with other HCV genotypes relative to type 1, but the improved long-term efficacy of IFN-αn1 compared with IFN-α2b was evident for all major HCV genotypes. It is concluded that IFN-αn1 and IFN-α2b have similar end-of-treatment response rates and safety profiles but the sustained response rate is higher with IFN-αn1. SR to IFN-α treatment are associated with clearance of HCV RNA, and histological improvement was maximal in patients who exhibited sustained ALT normalization and clearance of HCV RNA.
Combined Hormone Replacement Therapy Does Not Protect Women Against the Age-Related Decline in Endothelium-Dependent Vasomotor Function
Authors: Keld E. Sorensen, Inge Dorup, Anne P. Hermann, Leif Mosekilde
Journal: Circulation (1998)

Background —Improvement in endothelial function may be an important mechanism by which estrogen replacement therapy protects postmenopausal women against coronary artery disease. However, combined hormone replacement therapy is more frequently used owing to the risk of uterine cancer with estrogen-only therapy. Concurrent progesterone treatment may attenuate the beneficial effects of estrogens not only on the lipid profile but also on the endothelium. Methods and Results —We studied endothelial vasomotor function in 100 healthy postmenopausal women aged 53.3±2.9 years randomized to either combined hormone replacement therapy (n=46) or no substitution (n=54) 2.9±0.5 years earlier. In addition, 30 healthy premenopausal women aged 30.3±4.2 years were studied. With external ultrasound, brachial artery diameter was measured at rest, during reactive hyperemia (with increased flow causing endothelium-dependent dilation), and after sublingual nitroglycerin (causing endothelium-independent dilation). Compared with premenopausal women, flow-mediated dilation was significantly reduced in both postmenopausal groups. In the postmenopausal women, total cholesterol was lower in the treated women (5.66±0.83 versus 6.13±0.92 mmol/L; P =.025), whereas HDL cholesterol was similar (1.91±0.53 versus 1.85±0.46 mmol/L; P =NS). Dilation to flow and to nitroglycerin was similar in the two postmenopausal groups (flow: 2.5±2.9% versus 2.2±2.2%, P =NS; nitrate: 18.7±5.9% versus 17.2±6.2%, P =NS). Conclusions —Long-term combined oral hormone replacement therapy is without beneficial effects on endothelial vasomotor function in healthy postmenopausal women. This supports the view that progesterone may attenuate the beneficial effects of unopposed estrogen replacement.
A lipidomic analysis of nonalcoholic fatty liver disease
Authors: Puneet Puri, Rebecca A. Baillie, Michelle M. Wiest, Faridoddin Mirshahi, Jayanta Choudhury, Onpan Cheung, Carol Sargeant, Melissa J. Contos, Arun J. Sanyal
Journal: Hepatology (2007)

Abstract The spectrum of nonalcoholic fatty liver disease (NAFLD) includes a nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The specific types and amounts of lipids that accumulate in NAFLD are not fully defined. The free fatty acid (FFA), diacylglycerol (DAG), triacylglycerol (TAG), free cholesterol (FC), cholesterol ester, and phospholipid contents in normal livers were quantified and compared to those of NAFL and NASH, and the distribution of fatty acids within these classes was compared across these groups. Hepatic lipids were quantified by capillary gas chromatography. The mean (nmol/g of tissue) DAG (normal/NAFL/NASH: 1922 versus 4947 versus 3304) and TAG (13,609 versus 128,585 versus 104,036) increased significantly in NAFLD, but FFA remained unaltered (5533 versus 5929 versus 6115). There was a stepwise increase in the mean TAG/DAG ratio from normal livers to NAFL to NASH (7 versus 26 versus 31, P &lt; 0.001). There was also a similar stepwise increment in hepatic FC (7539 versus 10,383 versus 12,863, P &lt; 0.05 for NASH). The total phosphatidylcholine (PC) decreased in both NAFL and NASH. The FC/PC ratio increased progressively (0.34 versus 0.69 versus 0.71, P &lt; 0.008 for both). Although the levels for linoleic acid (18:2n-6) and α-linolenic acid (18:3n-3) remained unaltered, there was a decrease in arachidonic acid (20:4n-6) in FFA, TAG, and PC ( P &lt; 0.05 for all) in NASH. Eicosapentanoic acid (20:5n-3) and docosahexanoic acid (22:6n-3) were decreased in TAG in NASH. The n-6:n-3 FFA ratio increased in NASH ( P &lt; 0.05). Conclusions: NAFLD is associated with numerous changes in the lipid composition of the liver. The potential implications are discussed. (HEPATOLOGY 2007.)
Hepatitis B virus DNA prediction rules for hepatitis B e antigen–negative chronic hepatitis B
Authors: Jordan J. Feld, Melissa Ayers, Dahlia El-Ashry, Tony Mazzulli, Raymond Tellier, Jenny E. Heathcote
Journal: Hepatology (2007)

Abstract After hepatitis B e antigen (HBeAg) seroconversion, hepatitis B may become inactive or progress to HBeAg-negative hepatitis with persistent or intermittent alanine aminotransferase (ALT) elevation. The aim of this study was to prospectively identify factors predictive of the clinical course in HBeAg-negative chronic hepatitis B (CHB). Patients were stratified by ALT and HBeAg status and followed every 3 months for up to 5 years. Kaplan-Meier and Cox regression analysis using the change from normal ALT to elevated ALT as endpoints were performed to determine factors associated with ALT elevation/normalization. Seventy-four HBeAg-negative and 32 HBeAg-positive patients were prospectively evaluated. For HBeAg-negative patients, hepatitis B virus (HBV) DNA was predictive of future ALT. Only 1 patient with normal ALT and an HBV DNA value lower than 10,000 copies/mL developed an elevated ALT within the subsequent year, whereas 67% with an HBV DNA value greater than 100,000 copies/mL had a rise in ALT above normal within 1 year. Patients with a previous history of ALT elevation and longer follow-up at all levels of HBV DNA were more likely to experience ALT elevations. For HBeAg-negative patients with elevated ALT and all HBeAg-positive patients, HBV DNA did not predict future ALT. Other viral and host factors were not predictive of future ALT. Conclusion: HBeAg-negative CHB has a fluctuating course. HBV DNA values lower than 10,000 copies/mL predict persistently normal ALT for at least 1 year. Patients with HBV DNA values between 10,000 and 100,000 copies/mL can safely be followed at 6 monthly intervals, whereas HBV DNA values greater than 100,000 copies/mL are highly predictive of future ALT elevation and should prompt regular follow-up. (HEPATOLOGY 2007.)
Book: Difficult Diabetes
Authors: K. Baynes
Journal: BMJ (2001)

Eds Geoff Gill, John Pickup, Gareth Williams Blackwell Science, £59.50, pp 320 ISBN 0 632 05324 0 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Diabetes has scandalised me, scandalised and seduced in equal measure. The scandals have been the past lack of clinical trials with sensible outcome measures and the discrimination felt by people with diabetes from insurers, the Driver and Vehicle Licensing Authority, and employers. The seductions have been the nefarious clinical manifestations of diabetes and the complexity of understanding its pathophysiologies. Since the publication of the Diabetes Control and Complication Trial and the United Kingdom Prospective Diabetes Study, we all feel more justified in chasing the holy grail of a low HbA1c—some patients more assiduously and more obsessively than their doctors. Can we do this more effectively and … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Effects of a Low-Molecular-Weight Heparin on Thrombus Regression and Recurrent Thromboembolism in Patients with Deep-Vein Thrombosis
Authors: Hans Klaus Breddin, Viola Hach-Wunderle, Roumen Nakov, Vijay V. Kakkar
Journal: New England Journal of Medicine (2001)

Low-molecular-weight heparins are frequently used to treat venous thromboembolism, but optimal dosing regimens and clinical outcomes need further definition.In this multicenter, open-label study with blinded adjudication of end points, we randomly assigned patients with acute deep-vein thrombosis to one of three treatment regimens: intravenous administration of unfractionated heparin; subcutaneous administration of a low-molecular-weight heparin, reviparin, twice a day for one week; or subcutaneous administration of reviparin once a day for four weeks. The primary end point was evidence of regression of the thrombus on venography on day 21; secondary end points were recurrent venous thromboembolism, major bleeding within 90 days after enrollment, and death.Of the patients receiving unfractionated heparin, 40.2 percent (129 of 321) had thrombus regression, as compared with 53.4 percent (175 of 328) of patients receiving reviparin twice daily and 53.5 percent (167 of 312) of the patients receiving reviparin once daily. With regard to thrombus regression, reviparin administered twice daily was significantly more effective than unfractionated heparin (relative likelihood of thrombus regression, 1.28; 97.5 percent confidence interval, 1.08 to 1.52), as was reviparin administered once daily (relative likelihood, 1.29; 97.5 percent confidence interval, 1.08 to 1.53). Mortality and the frequency of episodes of major bleeding were similar in the three groups.In acute deep-vein thrombosis, reviparin regimens are more effective than unfractionated heparin in reducing the size of the thrombus. Reviparin is also more effective than unfractionated heparin for the prevention of recurrent thromboembolism and equally safe.
Complications of Fiberoptic Gastrointestinal Endoscopy - Five Years' Experience in a Central Hospital
Authors: O. Reiertsen, J. Skjøtø, C. D. Jacobsen, A. R. Rosseland
Journal: Endoscopy (1987)

Complications in relation to fiberoptic gastrointestinal endoscopy were recorded prospectively during the five-year period 1980-1984. Diagnostic esophago-gastroduodenoscopy (EGD) had non-fatal complications in ten out of 7,314 procedures (0.14%) and three deaths (0.04%). Therapeutic EGD had non-fatal complications in eight out of 440 procedures (1.8%) and two deaths (0.5%). Diagnostic endoscopic retrograde cholangiopancreatography (ERCP) had non-fatal complications in 15 out of 1,930 procedures (0.8%) and one death (0.05%). Therapeutic ERCP had non-fatal complications in 14 out of 554 procedures (2.5%) and six deaths (1.1%). Diagnostic colonoscopy had non-fatal complications in five out of 3,538 procedures (0.14%) and therapeutic colonoscopy in 21 out of 1,055 procedures (2.0%). There were no deaths in connection with diagnostic or therapeutic colonoscopy. The recommendations based on this series are: Put greater emphasis on a proper evaluation of indications and contraindications. Avoid sedation of patients with respiratory failure. If possible, postpone procedures which may cause bleeding in patients with impaired hemostasis until proper correction has been achieved.
Adefovir dipivoxil (ADV) for the treatment of patients with chronic hepatitis B (CHB) failing lamivudine (LAM) therapy
Authors: F. Zoulim, C. Trepo, T. Poynard, S. Pol, J.P. Zarski, P. Marcellin, M. Beaugrand, V. Stitruk, A. Trylesinski, K. Kleber, S. Van Doren, C. Brosgart
Journal: Journal of Hepatology (2003)
Pheochromocytoma, Prazosin, and Hypotension
Authors: ALLAN R. GLASS
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 September 1982Pheochromocytoma, Prazosin, and HypotensionALLAN R. GLASS, M.D., RIPLEY BALLOU, M.D.ALLAN R. GLASS, M.D.Search for more papers by this author, RIPLEY BALLOU, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-3-455_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In his excellent review of prazosin, Colucci (1) indicates that severe hypotension after the initial dose of prazosin ("first-dose phenomenon") is extremely rare if this dose is 1 mg or less. He also points out the usefulness of prazosin in the treatment of pheochromocytoma. However, his reference for this latter point (2) is the report of only one patient, who in fact did have a severe hypotensive response to an initial prazosin dose of only 1 mg. We also saw a patient with pheochromocytoma who developed severe hypotension in response to an initial prazosin dose of 1...References1. COLUCCI W. Alpha-adrenergic receptor blockade with prazosin: consideration of hypertension, heart failure, and potential new applications. Ann Intern Med. 1982;97:67-77. LinkGoogle Scholar2. WALLACEGILL JD. Prazosin in the diagnosis and treatment of pheochromocytoma. JAMA. 1978;240:2752-3. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ALLAN R. GLASS, M.D.; RIPLEY BALLOU, M.D.Affiliations: Walter Reed Army Medical Center Washington, DC 20012. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited by8 PhaeochromocytomaCorrection: Military Rank 1 September 1982Volume 97, Issue 3Page: 455-455KeywordsHypotensionPheochromocytoma ePublished: 1 December 2008 Issue Published: 1 September 1982 PDF downloadLoading ...
Dermatomyositis---how far to go!
Authors: S. H Till, A. C Jones
Journal: Annals of the Rheumatic Diseases (1998)

Case historyA 73 year old lady was referred with a four week history of proximal muscle weakness, myalgia and an erythematous, oedematous rash aVecting her face, upper chest, and back.Systemic enquiry and general examination was otherwise unremarkable.Initial investigations revealed a normal full blood count, erythrocyte sedimentation rate, C reactive protein, urea and electrolytes, liver function test, thyroid function tests, and urine analysis.The creatine kinase (CK) was increased to 3806 (normal range 24-170 U/l).Although Mi-2 antibody testing was not carried out she did have an IgG ANA level of 100.The rest of the autoimmune screen was negative.A needle muscle biopsy showed type 2-fibre atrophy with perivascular inflammatory changes but no direct evidence of myositis.She was given high dose oral prednisolone (60 mg daily) and received two pulses of intravenous methylprednisolone (1 g) and cyclophosphamide (1 g).Although the CK level responded rapidly to this treatment her clinical response was more gradual.Azathioprine was introduced and the prednisolone dose was gradually reduced to 30 mg daily with plans to reduce the dose further by 5 mg/month.She had a normal chest radiograph, sigmoidoscopy, barium enema, and abdominal ultrasound.Three months after the onset of her dermatomyositis she was seen urgently with acute thoracolumbar back pain.Radiographs confirmed slight vertebral wedging of D12.A myeloma screen and biochemical bone profile were normal.An isotope bone scan showed increased activity at D12 but no other areas of abnormality.We concluded that the probable explanation of these results, in a postmenopausal lady who had several other risk factors for osteoporosis (obesity, immobility, and high dose corticosteroids), was one of an osteoporotic fracture rather than an underlying malignant process.The dose of prednisolone was reduced from 10 to 7.5 mg daily and cyclical etidronate started.She had experienced nausea since starting azathioprine, this was withdrawn and her nausea settled.Three months later she was readmitted with a recurrence of her rash and myositis (CK, 666).Systemic enquiry, general examination, and routine investigations were normal.In particular there was neither a history of weight loss (which had actually increased with corticosteroids) nor gastrointestinal symptoms.A repeat