tbuckley/cabot-search huggingface dataset:
14C-urea breath test in C pylori gastritis.
Authors: E A Rauws, E A Royen, W Langenberg, J V Woensel, A A Vrij, G N Tytgat
Journal: Gut (1989)

14C-urea breath test was used to detect Campylobacter pylori colonisation in 129 consecutive non-ulcer dyspepsia patients. Fasting patients were given 3 microCi (110 kBq) of 14C-labelled urea after a test meal. Breath samples were collected at 10 minute intervals for 90 minutes and the C-14 activity was counted on a liquid scintillation analyser. Urea derived 14CO2 appears in the exhaled breath of Campylobacter pylori culture positive individuals within 20-30 minutes. Likelihood analysis revealed a most favourable cut off level of [0.07% dose 14C-urea/mmol CO2] multiplied by body weight at t = 40 minutes, to separate culture positive from culture negative subjects. Using this upper limit of normal, a positive likelihood ratio of 50 and a negative likelihood ratio of 0.05 was calculated. Sensitivity of the test was 95% and specificity 98%. The 14C-urea breath test is a simple, sensitive and non-invasive test, that detects viable C pylori microorganism and semiquantitatively assesses the bacterial load of C pylori colonisation. Administration of a single dose of colloidal bismuth subcitrate resulted in a rapid decrease in 14CO2 excretion, so this test can be used to confirm eradication of the bacterium in therapeutic trials without endoscopy, or need for culture.
Development and Split-Sample Validation of a Nomogram Predicting the Probability of Seminal Vesicle Invasion at Radical Prostatectomy
Authors: Andrea Gallina, Felix K.-H. Chun, Alberto Briganti, Shahrokh F. Shariat, Francesco Montorsi, Andrea Salonia, Andreas Erbersdobler, Patrizio Rigatti, Luc Valiquette, Hartwig Huland, Markus Graefen, Pierre I. Karakiewicz
Journal: European Urology (2007)
Coeliac disease--associated disorders and survival.
Authors: P Collin, T Reunala, E Pukkala, P Laippala, O Keyrilainen, A Pasternack
Journal: Gut (1994)

The associated diseases in 335 coeliac patients diagnosed 1980-90 were compared with age and sex matched control patients with various gastrointestinal symptoms. Endocrine disorders were found in 11.9% of coeliac and 4.3% of control patients (p = 0.0003). Coeliac patients had insulin dependent diabetes mellitus significantly (p = 0.0094) more often (5.4%) than control patients (1.5%). connective tissue diseases were found in 7.2% of coeliac and in 2.7% of control patients (p = 0.011). Sjögren9s syndrome occurred in 3.3% of coeliac patients and in 0.3% of controls (p = 0.0059). Autoimmune thyroid diseases were found in 5.4% and asthma in 3.6% of coeliac patients, but also in 2.7% and 3.6%, respectively, among control patients. The incidences of malignant diseases and the survival rate in coeliac patients were compared with those in the Finnish population. Ten coeliac patients developed a cancer during the follow up (mean 5.3 years, range 1-12) but none had a lymphoma. The risk of malignant diseases in coeliac patients did not differ from that in the Finnish population in general. Eleven coeliac patients died during the follow up. The five year survival rates of coeliac patients did not differ from those in the general population. At least 83% of the coeliac patients adhered strictly to the gluten free diet, which may explain the favourable outcome.
High Dose Concurrent Chemo-Radiation in Locally Advanced Pancreatic Cancers with Tomotherapy Based Imrt: a Phase II Study
Authors: Reena Engineer, Supreeta Arya, Supriya Chopra, Shaesta Mehta, Prachi Patil, Mahesh Goel, Shailesh Shrikhande, Shyam Shrivastava
Journal: Annals of Oncology (2013)
New structure enlivens interest in P2X receptors
Authors: Liam E. Browne, Lin-Hua Jiang, R. Alan North
Journal: Trends in Pharmacological Sciences (2010)

P2X receptors are ATP-gated membrane ion channels with multifarious roles, including afferent sensation, autocrine feedback loops, and inflammation. Their molecular operation has been less well elucidated compared with other ligand-gated channels (nicotinic acetylcholine receptors, ionotropic glutamate receptors). This will change with the recent publication of the crystal structure of a closed P2X receptor. Here we re-interpret results from 15 years of experiments using site-directed mutagenesis with a model based on the new structure. Previous predictions of receptor stoichiometry, the extracellular ATP binding site, inter-subunit contacts, and many details of the permeation pathway fall into place in three dimensions. We can therefore quickly understand how the channel operates at the molecular level. This is important not only for ion- channel aficionados, but also those engaged in developing effective antagonists at P2X receptors for potential therapeutic use.
Platelet Serotonin Reuptake Inhibition and Response to SSRIs in Depressed Adolescents
Authors: David A. Axelson, James M. Perel, Boris Birmaher, George Rudolph, Sharon Nuss, Linda Yurasits, Jeffrey Bridge, David A. Brent
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The authors examined platelet serotonin reuptake inhibition and response to selective serotonin reuptake inhibitor (SSRI) treatment in depressed adolescents. METHOD: Twenty-three depressed adolescents participating in pharmacokinetic studies of SSRIs had platelet serotonin reuptake measured before and after 14–28 days of treatment. The Clinical Global Impression (CGI) improvement rating was determined on the basis of all clinical information and was performed blind to the platelet data. RESULTS: Improvement in depressive symptoms as rated with the CGI improvement subscale was significantly associated with the percentage change in platelet serotonin reuptake inhibition from pre- to posttreatment. Improvement in depression was also associated with absolute decrease in platelet serotonin reuptake when adjusted for the magnitude of baseline reuptake. CONCLUSIONS: Platelet serotonin reuptake inhibition may be an appropriate surrogate biological marker for the pharmacodynamic activity of SSRIs in depressed adolescents.
Viral hepatitis surveillance and outbreak report is published in India
Authors: Cheryl Travasso
Journal: BMJ (2015)

Some 291 outbreaks and 804 782 cases of hepatitis infections occurred in India from 2011 to 2013, a national surveillance and outbreak data report on viral hepatitis has shown.1 In over 90% of cases, however, the causative agent was not identified.

Despite hepatitis infections being common, India has had a dearth of national data, so the government started collecting nationwide surveillance data in 2009 on hepatitis A and E infections, along with other epidemic-prone diseases, through the national Integrated Disease Surveillance Programme (IDSP).

The report presented data from 2011 to 2013 and showed a steady increase in the number of hepatitis cases reported every year, from 234 211 in 2011 …
Monoallelic Expression Determines Oncogenic Progression and Outcome in Benign and Malignant Brain Tumors
Authors: Erin J. Walker, Cindy Zhang, Pedro Castelo-Branco, Cynthia Hawkins, Wes Wilson, Nataliya Zhukova, Noa Alon, Ana Novokmet, Berivan Baskin, Peter Ray, Christiane Knobbe, Peter Dirks, Michael D. Taylor, Sidney Croul, David Malkin, Uri Tabori
Journal: Cancer Research (2011)

Abstract Although monoallelic expression (MAE) is a frequent genomic event in normal tissues, its role in tumorigenesis remains unclear. Here we carried out single-nucleotide polymorphism arrays on DNA and RNA from a large cohort of pediatric and adult brain tumor tissues to determine the genome-wide rate of MAE, its role in specific cancer-related genes, and the clinical consequences of MAE in brain tumors. We also used targeted genotyping to examine the role of tumor-related genes in brain tumor development and specifically examined the clinical consequences of MAE at TP53 and IDH1. The genome-wide rate of tumor MAE was higher than in previously described normal tissue and increased with specific tumor grade. Oncogenes, but not tumor suppressors, exhibited significantly higher MAE in high-grade compared with low-grade tumors. This method identified nine novel genes highly associated with MAE. Within cancer-related genes, MAE was gene specific; hTERT was most significantly affected, with a higher frequency of MAE in adult and advanced tumors. Clinically, MAE at TP53 exists only in mutated tumors and increases with tumor aggressiveness. MAE toward the normal allele at IDH1 conferred worse survival even in IDH1 mutated tumors. Taken together, our findings suggest that MAE is tumor and gene specific, frequent in brain tumor subtypes, and may be associated with tumor progression/aggressiveness. Further exploration of MAE at relevant genes may contribute to better understanding of tumor development and determine survival in brain tumor patients. Cancer Res; 72(3); 636–44. ©2011 AACR.
Rhenium-186 liposomes as convection-enhanced nanoparticle brachytherapy for treatment of glioblastoma
Authors: W. T. Phillips, B. Goins, A. Bao, D. Vargas, J. E. Guttierez, A. Trevino, J. R. Miller, J. Henry, R. Zuniga, G. Vecil, A. J. Brenner
Journal: Neuro-Oncology (2012)

Although external beam radiation is an essential component to the current standard treatment of primary brain tumors, its application is limited by toxicity at doses more than80 Gy. Recent studies have suggested that brachytherapy with liposomally encapsulated radionuclides may be of benefit, and we have reported methods to markedly increase the specific activity of rhenium-186 (186Re)–liposomes. To better characterize the potential delivery, toxicity, and efficacy of the highly specific activity of 186Re-liposomes, we evaluated their intracranial application by convection-enhanced delivery in an orthotopic U87 glioma rat model. After establishing an optimal volume of 25 µL, we observed focal activity confined to the site of injection over a 96-hour period. Doses of up to 1850 Gy were administered without overt clinical or microscopic evidence of toxicity. Animals treated with 186Re-liposomes had a median survival of 126 days (95% confidence interval [CI], 78.4–173 days), compared with 49 days (95% CI, 44–53 days) for controls. Log-rank analysis between these 2 groups was highly significant (P = .0013) and was even higher when 100 Gy was used as a cutoff (P < .0001). Noninvasive luciferase imaging as a surrogate for tumor volume showed a statistically significant separation in bioluminescence by 11 days after 100 Gy or less treatment between the experimental group and the control animals (χ2[1, N= 19] = 4.8; P = .029). MRI also supported this difference in tumor size. Duplication of tumor volume differences and survival benefit was possible in a more invasive U251 orthotopic model, with clear separation in bioluminescence at 6 days after treatment (χ2[1, N= 9] = 4.7; P = .029); median survival in treated animals was not reached at 120 days because lack of mortality, and log-rank analysis of survival was highly significant (P = .0057). Analysis of tumors by histology revealed minimal areas of necrosis and gliosis. These results support the potential efficacy of the highly specific activity of brachytherapy by 186Re-liposomes convection-enhanced delivery in glioma.
How should I interpret an interferon gamma release assay result for tuberculosis infection?: Table 1
Authors: Ibrahim Abubakar, Helen Ruth Stagg, Hilary Whitworth, Ajit Lalvani
Journal: Thorax (2013)

<h3>Background</h3> Interferon gamma release assays (IGRAs) are the first new diagnostic tests for latent tuberculosis (TB) infection (LTBI) since the century-old tuberculin skin test (TST). They are cell-mediated immune-based blood tests that have revolutionised LTBI diagnosis and are increasingly recommended by national guidelines. <h3>Objectives</h3> With the rapid expansion of the IGRA evidence-base in recent years, the limitations of IGRA and uncertainties in clinical interpretation of IGRA results have increasingly come into focus. In LTBI diagnosis these include: prognostic power of IGRAs relative to TST for quantifying risk of progression to active disease, false-negative rates in immunocompromised patients, the clinical meaning of IGRA reversion and the significance of the size of IGRA response. Furthermore, the role of IGRAs in the diagnostic work-up of active TB is unclear, and there is little evidence supporting use of the tests in anti-TB treatment monitoring. <h3>Methodological approach</h3> On-going large prospective longitudinal clinical endpoint cohort studies of active and latent TB will tackle some of the uncertainties regarding IGRAs. Here we discuss clinical practice and guidance in light of the current uncertainties, based on existing evidence. <h3>Conclusions and impact</h3> Current and planned clinical research will fill the gaps in the evidence-base, narrowing the areas of uncertainty and informing future policy. Translational research into next-generation IGRAs and new T cell-based diagnostic platforms will likely overcome the limitations of current IGRAs in the near future.
Potentiative effects of neutral proteinases in an inflamed lung: relationship of neutrophil procollagenase (proMMP-8) to plasmin, cathepsin G and tryptase in bronchiectasis in vivo
Authors: R Sepper, YT Konttinen, L Buo, KK Eklund, A Lauhio, T Sorsa, H Tschesche, AO Aasen, H Sillastu
Journal: European Respiratory Journal (1997)

We attempted to study the possible relationships between neutrophil-type procollagenase/pro-matrix metalloproteinase (MMP-8) and the serine proteinases plasmin, cathepsin G and tryptase in bronchiectasis. The presence of the plasmin/plasminogen system and plasmin-, cathepsin G- and tryptase-like activities were compared to the activity of endogenously activated MMP-8 in bronchoalveolar lavage (BAL) fluid in 38 bronchiectasis patients and in 14 healthy controls by means of immunohistochemistry, Western-blot and substrate-based functional assays. In contrast to cathepsin G- and tryptase-like activities, the plasmin/plasminogen activator system in BAL fluid was observed to have a relatively weak activation stage and no correlation with disease severity. Neither plasmin-like activities nor concentrations of plasminogen activators from the bronchiectatic patients differed significantly from the values of healthy controls. Immunolocation of plasminogen activator inhibitor-1 showed a marked, but not significant, increase in bronchiectatic lung as compared to controls. In contrast to cathepsin G- and tryptase-like activities, with their strong and significant correlation with endogenously activated collagenase (r=0.9; p=0.0001; and r=0.6; p=0.03, respectively), no correlations were observed between plasmin-like and endogenously activated collagenase (r=0.3; p=0.2) in bronchiectasis. These findings suggest that cathepsin G- and tryptase-like activities may act as potent pro-matrix metalloproteinase-8 activators in patients with bronchiectasis, whereas the plasminogen activator/plasmin cascade was shown to be down-regulated.
Colors with Functions: Elucidating the Biochemical and Molecular Basis of Carotenoid Metabolism
Authors: Johannes von Lintig
Journal: Annual Review of Nutrition (2010)

Carotenoids affect a rich variety of physiological functions in nature and are beneficial for human health, serving as antioxidants in lipophilic environments and blue light filters in the macula of human retina. These dietary compounds also serve as precursors of a unique set of apo-carotenoid cleavage products, including retinoids. Although knowledge about retinoid biology has tremendously increased, the metabolism of retinoids' parent precursors remains poorly understood. Recently, molecular players in carotenoid metabolism have been identified and biochemically characterized. Moreover, mutations in their corresponding genes impair carotenoid metabolism and induce various pathologies in animal models. Polymorphisms in these genes alter carotenoid and retinoid homeostasis in humans as well. This review summarizes our current knowledge about the molecular/biochemical basis of carotenoid metabolism and particularly the physiological role of carotenoids in retinoid-dependent physiological processes.
The Manitoba Inflammatory Bowel Disease Cohort Study: a prospective longitudinal evaluation of the use of complementary and alternative medicine services and products
Authors: Patricia Rawsthorne, Ian Clara, Lesley A Graff, Kylie I Bernstein, Rachel Carr, John R Walker, Jason Ediger, Linda Rogala, Norine Miller, Charles N Bernstein
Journal: Gut (2011)

<h3>Objective</h3> To determine the prevalence of complementary and alternative medicine (CAM) use over time in a population-based cohort of patients with inflammatory bowel disease (IBD). <h3>Methods</h3> The Manitoba IBD Cohort Study is a longitudinal, population-based study of multiple determinants of health outcomes in an IBD cohort. Participants completed semi-annual surveys, and annual in-person interviews. Enquiries about the use of 12 types of CAM service providers and 13 CAM products, based on items from a national survey, were included at months 0, 12, 30 and 54. <h3>Results</h3> Overall, 74% of respondents used a CAM service or product in the 4.5-year period, with approximately 40% using some type of CAM at each time point, and 14% using CAM consistently at every time point. There was a trend for women to use CAM more than men; there was no difference in CAM use between patients with Crohn9s disease and those with ulcerative colitis. The most often used CAM services (on average) were massage therapy (30%) and chiropractic (14%), physiotherapy (4%), acupuncture (3.5%) and naturopathy/homeopathy (3.5%). A wide range of CAM products were used, with <i>Lactobacillus acidophilus</i> (8%), fish and other oils (5.5%), glucosamine (4%) and chamomile (3.5%) as the most common. On average, only 18% of consumers used CAM for their IBD, so the majority chose it for other problems. There were no differences in psychological variables between CAM users and non-users. <h3>Conclusions</h3> Those with IBD commonly try CAM, although very few use these approaches regularly over the years. CAM is not usually used by patients with IBD for disease management, but clinicians should be aware that many will test the services and products.
Inhibition of p38 MAPK decreases myocardial TNF-alpha expression and improves myocardial function and survival in endotoxemia
Authors: T Peng
Journal: Cardiovascular Research (2003)

The role of p38 mitogen-activated protein kinase (MAPK) activation in lipopolysaccharide (LPS)-induced myocardial dysfunction has not been clearly defined. Our aim was to investigate the contribution of p38 MAPK in myocardial tumor necrosis factor-alpha (TNF-alpha) expression, cardiac function and survival during acute endotoxemia in mice.Acute endotoxemia was induced by LPS (10 mg/kg, i.p.) in mice. Two hours after LPS treatment, left ventricular (LV) function was assessed. Phosphorylation of p38 MAPK was measured by Western blotting. TNF-alpha mRNA and protein levels were determined by semi-quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.LPS rapidly increased phosphorylation of p38 MAPK, followed by TNF-alpha mRNA expression and protein expression in the LV myocardium. Pre-treatment of the p38 MAPK inhibitor SB202190 (2 mg/kg, i.p.) decreased TNF-alpha mRNA and protein by 65 and 36%, respectively (P<0.05). Immunohistochemical staining confirmed that cardiomyocytes were the major source of TNF-alpha production in the myocardium and blocking p38 MAPK activation inhibited TNF-alpha expression in response to LPS. Pre-treatment of SB202190 or a TNF-alpha antagonist etanercept (2 mg/kg, i.p) significantly reversed LPS-induced LV depression (P<0.05). LPS (20 mg/kg, i.p.) induced 94% mortality in mice within 72 h and pre-treatment with SB202190 and etanercept decreased LPS-induced mortality to 65 and 40%, respectively (P<0.01).p38 MAPK activation represents an important mechanism leading to myocardial TNF-alpha production and cardiac dysfunction during acute endotoxemia in mice. Our data suggest that p38 MAPK is a potential therapeutic target of endotoxemia.
A Community Mental Health Center, Regional Medical Program, and Joint Planning
Authors: ROBERT L. LEOPOLD, WILLIAM L. KISSICK
Journal: American Journal of Psychiatry (1970)

The West Philadelphia Community Mental Health Consortium, an enterprise in which six hospitals and a university cooperate to deliver comprehensive mental health care, is planning jointly with an area component of the Regional Medical Program to enlarge the consortium's service base for eventual delivery of general medical care. Collaboration with other government-funded programs is contemplated. The extent to which the consortium has involved community resources (including citizen leadership) in its operations is seen as its primary value in present and contemplated collaboration.
Identification and Functional Characterization of a New Human Kidney–Specific H+/Organic Cation Antiporter, Kidney-Specific Multidrug and Toxin Extrusion 2
Authors: Satohiro Masuda, Tomohiro Terada, Atsushi Yonezawa, Yuko Tanihara, Koshiro Kishimoto, Toshiya Katsura, Osamu Ogawa, Ken-ichi Inui
Journal: Journal of the American Society of Nephrology (2006)

A cDNA coding a new H+/organic cation antiporter, human kidney-specific multidrug and toxin extrusion 2 (hMATE2-K), has been isolated from the human kidney. The hMATE2-K cDNA had an open reading frame that encodes a 566–amino acid protein, which shows 94, 82, 52, and 52% identity with the hMATE2, hMATE2-B, hMATE1, and rat MATE1, respectively. Reverse transcriptase–PCR revealed that hMATE2-K mRNA but not hMATE2 was expressed predominantly in the kidney, and hMATE2-B was ubiquitously found in all tissues examined except the kidney. The immunohistochemical analyses revealed that the hMATE2-K as well as the hMATE1 was localized at the brush border membranes of the proximal tubules. HEK293 cells that were transiently transfected with the hMATE2-K cDNA but not hMATE2-B exhibited the H+ gradient–dependent antiport of tetraethylammonium (TEA). Transfection of hMATE2-B had no affect on the hMATE2-K–mediated transport of TEA. hMATE2-K also transported cimetidine, 1-methyl-4-phenylpyridinium (MPP), procainamide, metformin, and N1-methylnicotinamide. Kinetic analyses demonstrated that the Michaelis-Menten constants for the hMATE2-K–mediated transport of TEA, MPP, cimetidine, metformin, and procainamide were 0.83 mM, 93.5 μM, 0.37 mM, 1.05 mM, and 4.10 mM, respectively. Ammonium chloride–induced intracellular acidification significantly stimulated the hMATE2-K–dependent transport of organic cations such as TEA, MPP, procainamide, metformin, N1-methylnicotinamide, creatinine, guanidine, quinidine, quinine, thiamine, and verapamil. These results indicate that hMATE2-K is a new human kidney–specific H+/organic cation antiporter that is responsible for the tubular secretion of cationic drugs across the brush border membranes.
Previous forms of commissioning failed, government officials admit
Authors: A. O'Dowd
Journal: BMJ (2010)

Previous forms of commissioning in the NHS in England were failing to deliver the benefits they were supposed to and had to be dropped, Department of Health officials have told MPs.

Officials giving evidence to MPs on the parliamentary health select committee as part of its inquiry into commissioning said on 19 October that the benefits envisaged by previous approaches, such as world class commissioning and practice based commissioning, had not materialised.

The committee’s chairman, Stephen Dorrell, Conservative MP for Charnwood, said, “I want to look at what I regard as the government’s central conclusion from its [health] white paper, which is, if we want to make commissioning effective, primary care trusts as they are now have to be …