tbuckley/cabot-search huggingface dataset:
PTU-178 Pitfalls of Faecal Elastase Estimation
Authors: R Shah, A Varma, S Thomson, N Direkze
Journal: Gut (2013)

<h3>Introduction</h3> The faecal elastase test measures the concentration of the elastase-3B enzyme found in faecal matter with an enzyme-linked immunosorbent assay (ELISA). It is a good indicator of exocrine pancreatic status, and is less invasive and expensive than the secretin-cholecystokinin test, the current gold standard. Levels of faecal elastase lower than 200 μg/g of stool indicate an exocrine pancreatic insufficiency (EPI). <h3>Methods</h3> Aim: Faecal elastase is a marker for EPI particularly in chronic pancreatitis and pancreatic malignancy. Our aim was to outline the value of faecal elastase in patients with obscure diarrhoea. Methods: We retrospectively collected data of patients who had a faecal elastase test from June 2010 to 2012. We correlated the abnormal results with symptoms, findings on imaging and response to treatment. We also stratified these findings in patients with ultra low faecal elastase to assess whether the diagnostic yield was different. Paediatric patients were excluded from the study. <h3>Results</h3> There were a total of 72 abnormal results out of 523 in this 2 year study of which 33 (45%) patients had large volume diarrhoea. Of these, 26 (78%) patients had no therapeutic response to pancreatic enzyme supplements (PES) and had normal imaging, 4 had a response and in 3 we could not establish whether PES was trialled. Of the patients who responded to treatment, 2 had imaging suggestive of chronic pancreatitis. 9 of the patients who were investigated for steatorrhoea were on statins but had normal faecal elastase, normal cross sectional imaging and good response to treatment with PES 41 patients had ultra low faecal elastase levels ( &lt; 50µg/g), of these 32(78%) patients had significant pancreatic pathology whilst only 9(22%) had watery diarrhoea. <h3>Conclusion</h3> 1- A normal faecal elastase does not exclude EPI – as the 9 patients who were on statins had normal faecal elastase and pancreatic imaging and a dramatic response to PES. Other drugs like azathioprine, steroids causing EPI needs further investigation. 2- An ultra-low faecal elastase level (&lt;50 µg/g), is more likely to be related to significant pancreatic pathology with a response to treatment. Patients with watery diarrhoea are less likely to have a level this low. In these patients stool lyophilising or concentration should be performed before faecal elastase estimation. 3- In our patient group conditions like diabetes, coeliac disease, Addisons disease, gastrointestinal fistulas, short bowel syndrome, microscopic colitis, bile salt malabsorption and previous radiation all lead to falsely low levels without clinical correlation or response to treatment. Faecal elastase in this sub group should be interpreted with caution. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> The role of faecal elastase-1 in detecting exocrine pancreatic diseaseJohn S. Leeds, Kofi Oppong &amp; David S. Sanders
Mortality among twins after age 6: fetal origins hypothesis versus twin method
Authors: K. Christensen, J. W Vaupel, N. V Holm, A. I Yashin
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To test the validity of the fetal origins hypothesis and the classic twin method. <b>Design</b>: Follow up study of pairs of same sex twins in which both twins survived to age 6. <b>Setting</b>: Denmark. <b>Subjects</b>: 8495 twin individuals born 1870-1900, followed through to 31 December 1991. <b>Main outcome measures</b>: Mortality calculated on a cohort basis. <b>Results</b>: Mortality among twins and the general population was not significantly different except among females aged 60-89, in whom mortality among twins was 1.14 times (SE 0.03) higher than in the general population. Mortality among female dizygotic twins was 1.77 times (0.18) higher than among monozygotic twins at age 30.59. Otherwise, mortality for monozygotic and dizygotic twins did not consistently differ after age 6. <b>Conclusion</b>: According to the fetal origins hypothesis the risk of adult morbidity and mortality is heightened by retardation in intrauterine growth. Twins, and in particular monozygotic twins, experience growth retardation in utero. The findings in the present study suggest that the fetal origins hypothesis is not true for the retardation in intrauterine growth experienced by twins. Furthermore, the data are inconsistent with the underlying assumption of a recent claim that the classic twin method is invalid for studies of adult diseases. The present study is, however, based on the one third of all pairs of twins in which both twins survived to age 6. The possible impact of this selection can be evaluated in future studies of cohorts of younger twins with lower perinatal and infant mortality. <h3>Key messages</h3> Key messages It has been claimed that twin studies of adult diseases are invalid owing to the link between intrauterine development and adult diseases Contrary to the prediction from the fetal origins hypothesis this study found that mortality among twins and in the general population was similar after age 6 Contrary to the underlying assumption of the claim that the twin method is invalid, this study found that mortality in monozygotic and dizygotic twins was similar after age 6 This study suggests that the fetal origins hypothesis is not true for the retardation in intrauterine growth in these twin cohorts and that the hypothesis is no threat to the validity of the twin method
The relationship between obstructive sleep apnea syndrome and two common urological disorders
Authors: Soner Coban, Ege Gulec Balbay, Kamil Cam, Ali Kayikci, Oner Balbay
Journal: European Respiratory Journal (2012)

Erectile dysfunction (ED) and Lower Urinary Tract Symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) usually occur in older men. The aim was to investigate the relationship between Obstructive Sleep Apnea Syndrome (OSAS) and two urological common disorders.  Between January 2007 and April 2010, the men over the age of 50 admitted to the outpatient department of pulmonary diseases with suspected OSAS were selected. All patients had polysomniography analysis. A total of 29 patients having moderate and severe OSAS with apnea-hypopnea index (AHI)=15-30 (11 patients) and AHI>30 (18 patients), respectively were included in the first group.21 patients with AHI  Both groups were comparable with regard to age, PSA, prostate volume, and prostate size by digital rectal examination, IPSS values and uroflovmetry results. On the other hand, nocturia and IIEF results were remarkably different between two groups. The average number of nocturia was 1.47, and the mean score of IIEF was 15.48 in patients with OSAS. Those were 0.88 and 19.90 in the control group, respectively (p   In this study, IPSS and uroflovmetry values showed no difference between patients with and without OSAS. On the other hand, nocturia and IIEF results were both remarkably different in OSAS patients. As a result, OSAS was shown to be associated with nocturia and ED. Therefore, the patients with complaint of either nocturia or ED should be investigated for OSAS.
The expression of anti-poly(LGlu60, LPhe40) idiotypic determinants dictated by the gene products in the major histocompatibility complex.
Authors: U M Babu, P H Maurer
Journal: The Journal of Experimental Medicine (1981)

Antibodies raised in SWR/J mice (H-2q, Igc) to the random copolymer poly(LGlu60, LPhe40) (GPhe) were purified by immunoadsorbent chromatography and used to immunize a New Zealand red rabbit. The rabbit anti-idiotypic antiserum thus produced strongly inhibited the binding of 125I-GPhe by anti-GPhe antisera produced only in mice of H-2q haplotype, and had no effect on the binding of GPhe by anti-GPhe antisera produced in mice of other haplotypes, namely, H-2k and H-2p. The anti-idiotypic antiserum also inhibited the binding of GPhe by anti-GPhe-methylated bovine serum albumin antisera produced only in mice of H-2q haplotype. No linkage to Ig allotype was observed. The anti-GPhe antisera produced in F1 mice the anti-idiotypic antiserum demonstrating the dominant presence in these F1 mice of idiotypic determinants whose expression is dictated by the H-2q major histocompatibility complex (MHC). The anti-idiotypic antiserum also inhibited the binding of 125I-poly)LGlu56, LLys35, LPhe9) and 125I-GPhe antisera produced only in mice of H-2q haplotype. These specificities were also confirmed by the inhibition of the plaque-forming cells. It was concluded that the antibodies produced in mice of H-2q haplotype against GPhe and GLPhe share common idiotypic determinants that are recognized by the anti-idiotypic antiserum. A possible explanation for the unique findings that the expression of anti-GPhe idiotypic determinants in mice of H-2q haplotype are dictated by the gene product in the MHC is that the macrophages in mice of H-2q haplotype present unique determinants of GPhe polymer in the response process to GHphe.
Transplanted endothelial cells repopulate the liver endothelium and correct the phenotype of hemophilia A mice
Authors: Antonia Follenzi, Daniel Benten, Phyllis Novikoff, Louisa Faulkner, Sanj Raut, Sanjeev Gupta
Journal: Journal of Clinical Investigation (2008)

Transplantation of healthy cells to repair organ damage or replace deficient functions constitutes a major goal of cell therapy. However, the mechanisms by which transplanted cells engraft, proliferate, and function remain unknown. To investigate whether host liver sinusoidal endothelium could be replaced with transplanted liver sinusoidal endothelial cells, we developed an animal model of tissue replacement that utilized a genetic system to identify transplanted cells and induced host-cell perturbations to confer a proliferative advantage to transplanted cells. Under these experimental conditions, transplanted cells engrafted efficiently and proliferated to replace substantial portions of the liver endothelium. Tissue studies demonstrated that transplanted cells became integral to the liver structure and reacquired characteristic endothelial morphology. Characterization of transplanted endothelial cells by membrane markers and studies of cellular function, including synthesis and release of coagulation factor VIII, demonstrated that transplanted cells were functionally intact. Further analysis showed that repopulation of the livers of mice that model hemophilia A with healthy endothelial cells restored plasma factor VIII activity and corrected their bleeding phenotype. Our studies therefore suggest that transplantation of healthy endothelial cells should be considered for cell therapy of relevant disorders and that endothelial reconstitution with transplanted cells may offer an excellent paradigm for defining organ-specific pathophysiological mechanisms.
Is the 16S–23S rRNA Internal Transcribed Spacer Region a Good Tool for Use in Molecular Systematics and Population Genetics? A Case Study in Cyanobacteria
Authors: Sarah L. Boyer, Valerie R. Flechtner, Jeffrey R. Johansen
Journal: Molecular Biology and Evolution (2001)

We amplified, TA-cloned, and sequenced the 16S–23S internal transcribed spacer (ITS) regions from single isolates of several cyanobacterial species, Calothrix parietina, Scytonema hyalinum, Coelodesmium wrangelii, Tolypothrix distorta, and a putative new genus (isolates SRS6 and SRS70), to investigate the potential of this DNA sequence for phylogenetic and population genetic studies. All isolates carried ITS regions containing the sequences coding for two tRNA molecules (tRNA and tRNA). We retrieved additional sequences without tRNA features from both C. parietina and S. hyalinum. Furthermore, in S. hyalinum, we found two of these non-tRNA-encoding regions to be identical in length but different in sequence. This is the first report of ITS regions from a single cyanobacterial isolate not only different in configuration, but also, within one configuration, different in sequence. The potential of the ITS region as a tool for studying molecular systematics and population genetics is significant, but the presence of multiple nonidentical rRNA operons poses problems. Multiple nonidentical rRNA operons may impact both studies that depend on comparisons of phylogenetically homologous sequences and those that employ restriction enzyme digests of PCR products. We review current knowledge of the numbers and kinds of 16S–23S ITS regions present across bacterial groups and plastids, and we discuss broad patterns congruent with higher-level systematics of prokaryotes.
Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function
Authors: María Soler Artigas, Daan W Loth, Louise V Wain, Sina A Gharib, Ma'en Obeidat, Wenbo Tang, Guangju Zhai, Jing Hua Zhao, Albert Vernon Smith, Jennifer E Huffman, Eva Albrecht, Catherine M Jackson, David M Evans, Gemma Cadby, Myriam Fornage, Ani Manichaikul, Lorna M Lopez, Toby Johnson, Melinda C Aldrich, Thor Aspelund, Inês Barroso, Harry Campbell, Patricia A Cassano, David J Couper, Gudny Eiriksdottir, Nora Franceschini, Melissa Garcia, Christian Gieger, Gauti Kjartan Gislason, Ivica Grkovic, Christopher J Hammond, Dana B Hancock, Tamara B Harris, Adaikalavan Ramasamy, Susan R Heckbert, Markku Heliövaara, Georg Homuth, Pirro G Hysi, Alan L James, Stipan Jankovic, Bonnie R Joubert, Stefan Karrasch, Norman Klopp, Beate Koch, Stephen B Kritchevsky, Lenore J Launer, Yongmei Liu, Laura R Loehr, Kurt Lohman, Ruth J F Loos, Thomas Lumley, Khalid A Al Balushi, Wei Q Ang, R Graham Barr, John Beilby, John D Blakey, Mladen Boban, Vesna Boraska, Jonas Brisman, John R Britton, Guy G Brusselle, Cyrus Cooper, Ivan Curjuric, Santosh Dahgam, Ian J Deary, Shah Ebrahim, Mark Eijgelsheim, Clyde Francks, Darya Gaysina, Raquel Granell, Xiangjun Gu, John L Hankinson, Rebecca Hardy, Sarah E Harris, John Henderson, Amanda Henry, Aroon D Hingorani, Albert Hofman, Patrick G Holt, Jennie Hui, Michael L Hunter, Medea Imboden, Karen A Jameson, Shona M Kerr, Ivana Kolcic, Florian Kronenberg, Jason Z Liu, Jonathan Marchini, Tricia McKeever, Andrew D Morris, Anna-Carin Olin, David J Porteous, Dirkje S Postma, Stephen S Rich, Susan M Ring, Fernando Rivadeneira, Thierry Rochat, Avan Aihie Sayer, Ian Sayers, Peter D Sly, George Davey Smith, Akshay Sood, John M Starr, André G Uitterlinden, Judith M Vonk, S Goya Wannamethee, Peter H Whincup, Cisca Wijmenga, O Dale Williams, Andrew Wong, Massimo Mangino, Kristin D Marciante, Wendy L McArdle, Bernd Meibohm, Alanna C Morrison, Kari E North, Ernst Omenaas, Lyle J Palmer, Kirsi H Pietiläinen, Isabelle Pin, Ozren Polas̆ek, Anneli Pouta, Bruce M Psaty, Anna-Liisa Hartikainen, Taina Rantanen, Samuli Ripatti, Jerome I Rotter, Igor Rudan, Alicja R Rudnicka, Holger Schulz, So-Youn Shin, Tim D Spector, Ida Surakka, Veronique Vitart, Henry Völzke, Nicholas J Wareham, Nicole M Warrington, H-Erich Wichmann, Sarah H Wild, Jemma B Wilk, Matthias Wjst, Alan F Wright, Lina Zgaga, Tatijana Zemunik, Craig E Pennell, Fredrik Nyberg, Diana Kuh, John W Holloway, H Marike Boezen, Debbie A Lawlor, Richard W Morris, Nicole Probst-Hensch, Jaakko Kaprio, James F Wilson, Caroline Hayward, Mika Kähönen, Joachim Heinrich, Arthur W Musk, Deborah L Jarvis, Sven Gläser, Marjo-Riitta Järvelin, Bruno H Ch Stricker, Paul Elliott, George T O'Connor, David P Strachan, Stephanie J London, Ian P Hall, Vilmundur Gudnason, Martin D Tobin
Journal: Nature Genetics (2011)
Three-Dimensional Collagen I Promotes Gemcitabine Resistance in Pancreatic Cancer through MT1-MMP–Mediated Expression of HMGA2
Authors: Surabhi Dangi-Garimella, Seth B. Krantz, Morgan R. Barron, Mario A. Shields, Michael J. Heiferman, Paul J. Grippo, David J. Bentrem, Hidayatullah G. Munshi
Journal: Cancer Research (2010)

Abstract One of the hallmarks of human pancreatic ductal adenocarcinoma (PDAC) is its pronounced type I collagen-rich fibrotic reaction. Although recent reports have shown that the fibrotic reaction can limit the efficacy of gemcitabine chemotherapy, the underlying mechanisms remain poorly understood. In this article, we show that the type I collagen allows PDAC cells to override checkpoint arrest induced by gemcitabine. Relative to cells grown on tissue culture plastic, PDAC cells grown in 3-dimensional collagen microenvironment have minimal Chk1 phosphorylation and continue to proliferate in the presence of gemcitabine. Collagen increases membrane type 1 matrix metalloproteinase (MT1-MMP)–dependent ERK1/2 phosphorylation to limit the effect of gemcitabine. Collagen also increases MT1-MMP–dependent high mobility group A2 (HMGA2) expression, a nonhistone DNA-binding nuclear protein involved in chromatin remodeling and gene transcription, to attenuate the effect of gemcitabine. Overexpression of MT1-MMP in the collagen microenvironment increases ERK1/2 phosphorylation and HMGA2 expression, and thereby further attenuates gemcitabine-induced checkpoint arrest. MT1-MMP also allows PDAC cells to continue to proliferate in the presence of gemcitabine in a xenograft mouse model. Clinically, human tumors with increased MT1-MMP show increased HMGA2 expression. Overall, our data show that collagen upregulation of MT1-MMP contributes to gemcitabine resistance in vitro and in a xenograft mouse model, and suggest that targeting MT1-MMP could be a novel approach to sensitize pancreatic tumors to gemcitabine. Cancer Res; 71(3); 1019–28. ©2010 AACR.
Comment on: Chakkera et al. Pretransplant Risk Score for New-Onset Diabetes After Kidney Transplantation. Diabetes Care 2011;34:2141–2145
Authors: Tone Gretland Valderhaug, Henrik Andreas Bergrem, Trond Jenssen, Jøran Hjelmesæth
Journal: Diabetes Care (2012)

We read with interest the article by Chakkera et al. (1), which presented a pretransplant risk score to help identify subjects who might develop new-onset diabetes after kidney transplantation (NODAT). Although the authors briefly discussed the limitations of their diagnostic criteria of NODAT, they did not elaborate on how the exclusion of an oral glucose tolerance test (OGTT) might impact the external validity and generalizability of the study.

First, the authors documented the absence of diabetes before transplantation by assessing the forms submitted to the United Network for Organ Sharing. In addition, at pretransplant testing all patients had a fasting plasma glucose (FPG) <126 mg/dL (7.0 mmol/L) and a …
The effect of age, sex, and concussion history on preseason ImPACT values of elite Canadian youth ice hockey players
Authors: Carly D McKay, Brian L Brooks, Willem H Meeuwisse, Martin Mrazik, Andrea L Jubinville, Carolyn A Emery.
Journal: British Journal of Sports Medicine (2013)

Objective To examine the effect of age, sex, and concussion history on preseason scores from the ImPACT computer-based neurocognitive test battery in elite 12–17-year-old ice hockey players. Design Cross-sectional. Setting Participants were recruited from the most elite divisions (AA, AAA) of youth ice hockey leagues in Calgary and Edmonton, Alberta, Canada. Participants 714 Bantam (ages 12–14) (47 female, 161 male) and Midget (ages 15–17) (67 female, 439 male) hockey players. Assessment of Risk Factors Players completed a preseason ImPACT test before the 2011–2012 season. Outcome Measures Outcomes were composite scores &lt;25th percentile (based on sample distribution) for verbal memory, visual memory and impulse control, and scores &gt;75th percentile for visual motor speed, reaction time, and total symptoms. Results Using multivariate Poisson regression, adjusted for cluster by team, those aged 16–17 years were less likely to score &lt;25th percentile in verbal memory (IRR=0.85; 95% CI 0.78 to 0.98) or &gt;75th percentile in reaction time (IRR=0.79; 95% CI 0.69 to 0.91), but were more likely to score &gt;75th percentile in visual motor speed (IRR=1.27; 95% CI 1.17 to 1.37) and total symptoms (IRR=1.14; 95% CI 1.04 to 1.25). Males were less likely to score &lt;25th percentile in verbal memory (IRR=0.85; 95% CI 0.78 to 0.92), but more likely to score &gt;75th percentile in visual motor speed (IRR=1.20; 95% CI 1.05 to 1.38) and total symptoms (IRR=1.21; 95% CI 1.02 to 1.44). Previous concussion was not predictive of ImPACT scores in the poorest quartile on any subscale. Conclusions Age and sex influence preseason ImPACT scores, although concussion history does not appear to have an effect. Acknowledgements The Sport Injury Prevention Research Centre is one of the International Research Centres for Prevention of Injury and Protection of Athlete Health supported by the International Olympic Committee. We acknowledge the funding from the McCarthy Tetrault Award, Alberta Innovates Health Solutions, and the Alberta Children's Hospital Research Institute for Child and Maternal Health. Competing interests Author B Brooks declares research grant support from CNS Vital Signs (neurocognitive test battery publisher) and PAR, Inc (test publisher).
Epidermal Growth Factor Enemas with Oral Mesalamine for Mild-to-Moderate Left-Sided Ulcerative Colitis or Proctitis
Authors: Atul Sinha, Jeremy M.D. Nightingale, Kevin P. West, Jorge Berlanga-Acosta, Raymond J. Playford
Journal: New England Journal of Medicine (2003)

Epidermal growth factor (EGF) is a potent mitogenic peptide produced by salivary glands. We examined whether EGF enemas are an effective treatment for active left-sided ulcerative colitis and ulceration limited to the rectum (proctitis).In a randomized, double-blind clinical trial conducted at Leicester Royal Infirmary, 12 patients with mild-to-moderate left-sided ulcerative colitis received daily enemas of 5 microg of EGF in 100 ml of an inert carrier and 12 received daily enemas with carrier alone for 14 days. All also began to receive 1.2 g of oral mesalamine per day or had their dose increased by 1.2 g per day. Patients were assessed clinically at 0, 2, 4, and 12 weeks and by sigmoidoscopy and biopsy at 0, 2, and 4 weeks. The primary end point was disease remission (defined by a St. Marks score of 4 or less without sigmoidoscopic evidence of inflammation) at two weeks. Secondary end points were clinically significant improvements in disease activity (defined by a decrease of more than 3 points in the St. Marks score or the ulcerative colitis disease-activity index) at two and four weeks. Analyses were performed according to the intention-to-treat principle.After two weeks, 10 of the 12 patients given EGF enemas were in remission, as compared with 1 of 12 in the control group (83 percent vs. 8 percent, P<0.001). At the 2-week assessment, disease-activity scores, sigmoidoscopic score, and histologic scores were all significantly better in the EGF group than in the placebo group (P<0.01 for all comparisons), and this benefit was maintained at 4 weeks and at 12 weeks.This study provides preliminary data suggesting that EGF enemas are an effective treatment for active left-sided ulcerative colitis.