tbuckley/cabot-search huggingface dataset:
Value of MR colonography for assessment of inflammatory bowel disease? Believe what you see--see what you believe
Authors: C Gasche
Journal: Gut (2005)

Should magnetic resonance colonography be used to assess colonic inflammation in known inflammatory bowel disease or for assessment of inflammatory bowel disease?

“ libenter homines id quod volunt credunt .” (Men willingly believe what they wish). Gaius Julius Caesar, De Bello Gallico, Book 3. 

Imaging methods in inflammatory bowel disease (IBD) are used to serve two purposes: firstly, to establish the diagnosis in suspected IBD, and secondly, to gain information for correct management in known cases of IBD. To date, colonoscopy with biopsy remains the method of first choice to diagnose IBD. Discrete morphological alterations such as erythema, oedema, and granularity of the mucosa, small erosions, or aphthous ulcers can be reliably depicted by videoendoscopy and subsequently confirmed by histopathology. In established IBD however, patients and physicians are reluctant to perform repeated colonoscopies because of the invasive nature of the test and the inability to assess extraluminal complications in Crohn’s disease, including enteric fistulae or abscesses. For this purpose, cross sectional imaging methods have gained increasing importance in the past years.1 The question arises as to whether advancement in technology (multislice computed tomography or magnetic resonance imaging (MRI) scans) may also enable assessment of the mucosal inflammation in IBD, thereby potentially replacing endoscopy and biopsy at some point in the future.

This question was approached by two independent groups from Germany in this issue of Gut .2,3 The group from Essen2 reported on a two phase investigation …
Research in medical education: three decades of progress
Authors: G. Norman
Journal: BMJ (2002)

The specialty of research in medical education began just over three decades ago with a small group of clinicians and educational researchers at the medical school in Buffalo, New York.Since that time it has expanded worldwide.This paper is a personal reflection on how this research has informed our understanding of learning, teaching, and assessment in medicine. Measuring progressIn medicine, indicators of scientific progress might be measured by objective indicators such as death from cardiovascular disease.In education such "hard" evidence may be lacking for several reasons.2][3][4][5] Secondly, a curriculum is not like a drug, which can be given at standard doses, but instead contains many components, delivered with variable quality by different teachers.Finally, the time between learning and important outcomes may be so long that the effects of the curriculum are obscuredalthough not always.
Contrasts in Oxidative Potential and Other Particulate Matter Characteristics Collected Near Major Streets and Background Locations
Authors: Hanna Boogaard, Nicole A.H. Janssen, Paul H. Fischer, Gerard P.A. Kos, Ernie P. Weijers, Flemming R. Cassee, Saskia C. van der Zee, Jeroen J. de Hartog, Bert Brunekreef, Gerard Hoek
Journal: Environmental Health Perspectives (2011)

Measuring the oxidative potential of airborne particulate matter (PM) may provide a more health-based exposure measure by integrating various biologically relevant properties of PM into a single predictor of biological activity.We aimed to assess the contrast in oxidative potential of PM collected at major urban streets and background locations, the associaton of oxidative potential with other PM characteristics, and the oxidative potential in different PM size fractions.Measurements of PM with aerodynamic diameter ≤ 10 μm (PM10), PM with aerodynamic diameter ≤ 2.5 μm (PM2.5), soot, elemental composition, and oxidative potential of PM were conducted simultaneously in samples from 8 major streets and 10 urban and suburban background locations in the Netherlands. Six 1-week measurements were performed at each location over a 6-month period in 2008. Oxidative potential was measured as the ability to generate hydroxyl radicals in the presence of hydrogen peroxide in all PM10 samples and a subset of PM2.5 samples.The PM10 oxidative potential of samples from major streets was 3.6 times higher than at urban background locations, exceeding the contrast for PM mass, soot, and all measured chemical PM characteristics. The contrast between major streets and suburban background locations was even higher (factor of 6.5). Oxidative potential was highly correlated with soot, barium, chromium, copper, iron, and manganese. Oxidative potential of PM10 was 4.6 times higher than the oxidative potential of PM2.5 when expressed per volume unit and 3.1 times higher when expressed per mass unit.The oxidative potential of PM near major urban roads was highly elevated compared with urban and suburban background locations, and the contrast was greater than that for any other measured PM characteristic.
Studies on the Pathogenesis of an Immune Defect in Multiple Myeloma
Authors: Teresa Paglieroni, Malcolm R. MacKenzie
Journal: Journal of Clinical Investigation (1977)

The reduced capacity of patients with multiple myeloma to respond to antigen challenge is well recognized. Response to antigen involves antigen recognition, cell proliferation, and synthesis and secretion of antibody. This study examines this sequence of events in peripheral blood lymphocytes from untreated and treated patients with myeloma, from individuals with benign monoclonal gammopathy, and from normal healthy donors. Antigen-binding capacity was assessed by testing the ability of lymphocytes to bind radio-labeled pneumococcal polysaccharide, tetanus toxoid, or diptheria toxin. The in vitro proliferative response to these antigens as well as to pokeweed mitogen and streptokinase-streptodornase was evaluated. The secretion of immunoglobulin in response to pneumococcal polysaccharide, tetanus toxoid, and pokeweed mitogen by 2-4 x 10(6) lymphocytes in 7-day cultures was determined. The effects of coculture of myeloma peripheral blood lymphocytes and normal peripheral blood lymphocytes on immunoglobulin production and mixed leukocyte reactions were explored. All myeloma patients had normal numbers (3-8/5,000 cells) of antigen-binding cells. However, most showed a diminished antigen-induced blast transformation as measured by uptake of [(125)I]5-iodo-2'-deoxyuridine in culture. Immunoglobulin production in response to specific antigen in myeloma lymphocytes was 30-80% less than in normal lymphocytes. Immunoglobulin synthesis and mixed leukocyte responses by normal peripheral blood lymphocytes could be suppressed by myeloma lymphocytes. Multiple suppressor populations were present. Thus, the immune defect in myeloma is beyond the antigen recognition step and involves both the proliferation of antigen-sensitive cells and immunoglobulin production. Further suppressive effects are imposed on normal cells, implying defects in immunoregulation in this disease.
No influence of airway heat flux on airflow-induced bronchospasm
Authors: SD Fuller, AN Freed
Journal: European Respiratory Journal (1992)

We used a canine model of airway reactivity to examine the role of airway heat flux in the response to dry air challenge. Airflow-induced bronchospasm (AIB) was assessed by measuring collateral system resistance (Rcs) with a wedged bronchoscope technique in anaesthetized mechanically ventilated dogs. We manipulate post-challenge airway heat flux by exposing peripheral airways to cool dry air (23.9 +/- 0.3 degrees C, 0.8 +/- 0.2 mgH2O.l-1), cool humid air (24.2 +/- 0.2 degrees C, 21.5 +/- 0.3 mgH2O.l-1), or warm humid air (35.3 +/- 0.4 degrees C, 40.6 +/- 0.3 mgH2O.l-1) during the recovery period (n = 14) following a high flow challenge (1,500 ml.min-1 for 2 min) with cool dry air. In a second series of experiments (n = 6), we attempted to further exaggerate airway heat flux during challenge by exposing peripheral airways to warm humid air during both baseline and recovery periods. In comparison to control (i.e. treatment with cool dry air before and after challenge), treatment with warm humid air during recovery period produced a small but significant attenuation (p less than 0.01) in Rcs. Cool humid air during recovery had no affect on Rcs following challenge. Warm humid air during both baseline and recovery tended to attenuate Rcs after challenge (p less than 0.05). We conclude that airway heat flux in itself has no significant physiological affect on AIB in the canine lung periphery.
Macroregenerative Nodules and Hepatocellular Carcinoma in Forty–Four Sequential Adult Liver Explants With Cirrhosis
Authors: Neil D. Theise, Myron Schwartz, Charles Miller, Swan N. Thung
Journal: Hepatology (1992)

Macroregenerative nodules, also called nodules of adenomatous hyperplasia, have been well documented in Japan. Extensive studies support the hypothesis that in the Japanese population these lesions represent a possible pathway for hepatocarcinogenesis. However, reporting of these lesions in non-Japanese populations has so far been rare. We examined 44 sequential cirrhotic hepatectomy specimens from adult patients who underwent orthotopic liver transplantation at our institution. All livers were serially sectioned every 0.5 cm. Macroregenerative nodules were defined as regenerative nodules at least 1 cm in diameter. Forty-eight macroregenerative nodules were found in 11 livers (25% of livers). The antecedent diseases in these livers included hepatitis C (3), alcoholism (2), primary biliary cirrhosis (2) (one with iron overload), cryptogenic cirrhosis (2), hepatitis B (1) and alpha 1-antitrypsin deficiency (1). The macroregenerative nodules often differed from the surrounding nodular parenchyma in color, texture or the degree to which they bulged beyond the cut liver surface. Three livers contained grossly apparent hepatocellular carcinomas. Microscopically, macroregenerative nodules could be classified as those with (type 2) and without (type 1) dysplasia. Four livers had type 1 lesions, two had type 2 lesions and five had lesions of both types. We found 36 type 1 lesions in all and 12 type 2 lesions, 3 containing foci of microscopic carcinoma. All hepatocellular carcinomas arose in livers containing macroregenerative nodules (either type). Liver cell dysplasia, large-cell or small-cell, was observed in cirrhotic nodules of 27 livers. Microscopic or macroscopic hepatocellular carcinoma occurred in three livers with large-cell but not small-cell dysplasia and in one liver without dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)
INNO-406, a novel BCR-ABL/Lyn dual tyrosine kinase inhibitor, suppresses the growth of Ph+ leukemia cells in the central nervous system, and cyclosporine A augments its in vivo activity
Authors: Asumi Yokota, Shinya Kimura, Satohiro Masuda, Eishi Ashihara, Junya Kuroda, Kiyoshi Sato, Yuri Kamitsuji, Eri Kawata, Yasuyuki Deguchi, Yoshimasa Urasaki, Yasuhito Terui, Martin Ruthardt, Takanori Ueda, Kiyohiko Hatake, Ken-ichi Inui, Taira Maekawa
Journal: Blood (2006)
Obtaining real-world evidence: the Salford Lung Study
Authors: John P New, Nawar Diar Bakerly, David Leather, Ashley Woodcock
Journal: Thorax (2014)

We need to assess clinical treatments in real-life settings outside of randomised controlled trials (RCTs). Pragmatic RCT (pRCT) data can supplement RCTs by providing effectiveness information to support healthcare decisions. Electronic health records can facilitate concurrent safety monitoring and data collection without direct patient contact for large randomised study populations in pRCTs. The Salford Lung Study is the world9s first phase III pRCT in asthma and chronic obstructive pulmonary disease (COPD), which aims to randomise over 7000 patients. This paper describes the hurdles overcome and the enormous effort and resource required to establish this comparative effectiveness study of a prelicence intervention. <h3>GlaxoSmithKline protocol</h3> HZC115151 <h3>Asthma study clinicaltrials.gov registration</h3> NCT01706198 <h3>COPD study clinicaltrials.gov registration</h3> NCT01551758
International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to Therapy
Authors: Maria P. Abbracchio, Geoffrey Burnstock, Jean-Marie Boeynaems, Eric A. Barnard, José L. Boyer, Charles Kennedy, Gillian E. Knight, Marta Fumagalli, Christian Gachet, Kenneth A. Jacobson, Gary A. Weisman
Journal: Pharmacological Reviews (2006)

There have been many advances in our knowledge about different aspects of P2Y receptor signaling since the last review published by our International Union of Pharmacology subcommittee. More receptor subtypes have been cloned and characterized and most orphan receptors deorphanized, so that it is now possible to provide a basis for a future subdivision of P2Y receptor subtypes. More is known about the functional elements of the P2Y receptor molecules and the signaling pathways involved, including interactions with ion channels. There have been substantial developments in the design of selective agonists and antagonists to some of the P2Y receptor subtypes. There are new findings about the mechanisms underlying nucleotide release and ectoenzymatic nucleotide breakdown. Interactions between P2Y receptors and receptors to other signaling molecules have been explored as well as P2Y-mediated control of gene transcription. The distribution and roles of P2Y receptor subtypes in many different cell types are better understood and P2Y receptor-related compounds are being explored for therapeutic purposes. These and other advances are discussed in the present review.
Use of ECT for the Inpatient Treatment of Recurrent Major Depression
Authors: Mark Olfson, Steven Marcus, Harold A. Sackeim, James Thompson, Harold Alan Pincus
Journal: American Journal of Psychiatry (1998)

The authors' goals were to determine the frequency and distribution of ECT for general hospital inpatients with recurrent major depression and to estimate the effects of prompt ECT on the length and cost of inpatient care.Data from the 1993 Healthcare Cost and Utilization Project were analyzed to determine the rate of ECT use for adult inpatients with a principal discharge diagnosis of major depression, recurrent. Associations between prompt initial use of ECT (in the first 5 hospital days) and length and cost of inpatient care were examined before and after control for sociodemographic, diagnostic, and hospital organizational characteristics.An estimated 9.4% of general hospital adult inpatients with a principal diagnosis of recurrent major depression received ECT in the survey year. A majority (59.2%) of these received their initial ECT session within the first 5 days after hospital admission. In univariate analyses, the likelihood of receiving ECT was greater for older patients, whites, privately insured individuals, and patients who lived in more affluent areas. Patients who received ECT tended to have relatively long and costly admissions. After control for several demographic, diagnostic, and hospital organizational characteristics, prompt ECT (as compared with delayed ECT or none) was associated with significantly shorter and less costly inpatient care.The longer stays and higher treatment costs associated with ECT may be a consequence of patient selection. When patient selection is taken into account, prompt administration of ECT is associated with shorter and less costly hospital stays. Nonetheless, economically disadvantaged patients are relatively unlikely to receive this treatment.
Intratumoral Mediated Immunosuppression is Prognostic in Genetically Engineered Murine Models of Glioma and Correlates to Immunotherapeutic Responses
Authors: Ling-Yuan Kong, Adam S. Wu, Tiffany Doucette, Jun Wei, Waldemar Priebe, Gregory N. Fuller, Wei Qiao, Raymond Sawaya, Ganesh Rao, Amy B. Heimberger
Journal: Clinical Cancer Research (2010)

Preclinical murine model systems used for the assessment of therapeutics have not been predictive of human clinical responses, primarily because their clonotypic nature does not recapitulate the heterogeneous biology and immunosuppressive mechanisms of humans. Relevant model systems with mice that are immunologically competent are needed to evaluate the efficacy of therapeutic agents, especially immunotherapeutics.Using the RCAS/Ntv-a system, mice were engineered to coexpress platelet-derived growth factor B (PDGF-B) receptor + B-cell lymphoma 2 (Bcl-2) under the control of the glioneuronal specific Nestin promoter. The degree and type of tumor-mediated immunosuppression were determined in these endogenously arising gliomas on the basis of the presence of macrophages and regulatory T cells. The immunotherapeutic agent WP1066 was tested in vivo to assess therapeutic efficacy and immunomodulation.Ntv-a mice were injected with RCAS vectors to express PDGF-B + Bcl-2, resulting in both low- and high-grade gliomas. Consistent with observations in human high-grade gliomas, mice with high-grade gliomas also developed a marked intratumoral influx of macrophages that was influenced by tumor signal transducer and activator of transduction 3 (STAT3) expression. The presence of intratumoral F4/80 macrophages was a negative prognosticator for long-term survival. In mice coexpressing PDGF-B + Bcl-2that were treated with WP1066, there was 55.5% increase in median survival time (P < 0.01), with an associated inhibition of intratumoral STAT3 and macrophages.Although randomization is necessary for including mice in a therapeutic trial, these murine model systems are more suitable for testing therapeutics, especially immunotherapeutics, in the context of translational studies.
On the behavioural interpretation of neurophysiological observation
Authors: Donald R. J. Laming
Journal: Behavioral and Brain Sciences (2000)

Examples of terror generated by an aircraft disaster, of human courtship behaviour, and of the application of laboratory techniques to the commercial training of animals suggest (1) that emotion is simply the subjective counterpart of (objective) motivation (so that separate brain mechanisms would be an embarrassment) and (2) the apparent involvement of reward and punishment is a consequence of the excessively narrow range of experimental procedures used and has no foundation in the design of the brain.
Mode of Death in Patients With Heart Failure and a Preserved Ejection Fraction
Authors: Michael R. Zile, William H. Gaasch, Inder S. Anand, Markus Haass, William C. Little, Alan B. Miller, Jose Lopez-Sendon, John R. Teerlink, Michel White, John J. McMurray, Michel Komajda, Robert McKelvie, Agata Ptaszynska, Scott J. Hetzel, Barry M. Massie, Peter E. Carson
Journal: Circulation (2010)

Background— The mode of death has been well characterized in patients with heart failure and a reduced ejection fraction; however, less is known about the mode of death in patients with heart failure and a preserved ejection fraction (HFPEF). The purpose of this study was to examine the mode of death in patients with HFPEF enrolled in the Irbesartan in Heart Failure With Preserved Ejection Fraction Study (I-Preserve) trial and to determine whether irbesartan altered the distribution of mode of death in HFPEF. Methods and Results— All deaths were reviewed by a clinical end-point committee, and the mode of death was assigned by consensus of the members. The annual mortality rate was 5.2% in the I-Preserve trial. There were no significant differences in mortality rate between the placebo and irbesartan groups. The mode of death was cardiovascular in 60% (including 26% sudden, 14% heart failure, 5% myocardial infarction, and 9% stroke), noncardiovascular in 30%, and unknown in 10%. There were no differences in the distribution of mode-specific mortality rates between placebo and irbesartan. Conclusions— Sixty percent of the deaths in patients with HFPEF were cardiovascular, with sudden death and heart failure death being the most common. Treatment with irbesartan did not affect overall mortality or the distribution of mode-specific mortality rates. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.
Comparative Molecular Population Genetics of the Xdh Locus in the Cactophilic Sibling Species Drosophila buzzatii and D. koepferae
Authors: R. Piccinali
Journal: Molecular Biology and Evolution (2003)

The Xdh (rosy) gene is one of the best studied in the Drosophila genus from an evolutionary viewpoint. Here we analyze nucleotide variation in a 1875-bp fragment of the second exon of Xdh in Argentinian populations of the cactophilic D. buzzatii and its sibling D. koepferae. The major electrophoretic alleles of D. buzzatii not only lack diagnostic amino acids in the region studied but also differ on average from each other by four to 13 amino acid changes. Our data also suggest that D. buzzatii populations belonging to different phytogeographic regions are not genetically differentiated, whereas D. koepferae exhibits a significant pattern of population structure. The Xdh region studied is twice as polymorphic in D. buzzatii as in D. koepferae. Differences in historical population size or in recombinational environment between species could account for the differences in the level of nucleotide variation. In both species, the Xdh region exhibits a great number of singletons, which significantly departs from the frequency spectrum expected under neutrality for nonsynonymous sites and also for synonymous sites in D. buzzatii. These excesses of singletons could be the signature of a recent population expansion in D. buzzatii, whereas they may be simply explained as the result of negative selection in D. koepferae.
Caffeine Intake, Tolerance, and Withdrawal in Women: A Population-Based Twin Study
Authors: Kenneth S. Kendler, Carol A. Prescott
Journal: American Journal of Psychiatry (1999)

Caffeine is by far the most commonly consumed psychoactive substance. The use and abuse of most other licit and illicit psychoactive drugs have been shown to be substantially heritable. However, the impact of genetic factors on caffeine consumption, heavy use, intoxication, tolerance, and withdrawal is largely unknown.Caffeine consumption, in the form of brewed coffee, instant coffee, tea, and caffeinated soft drinks, as well as caffeine intoxication, tolerance, and withdrawal, were assessed by personal interviews of 1,934 individual twins from female-female pairs ascertained from the population-based Virginia Twin Registry. The sample included both members of 486 monozygotic and 335 dizygotic pairs. Twin resemblance was assessed by probandwise concordance, odds ratios, and tetrachoric correlations. Biometrical model fitting was also performed.The resemblance in twin pairs for total caffeine consumption, heavy caffeine use, caffeine intoxication, caffeine tolerance, and caffeine withdrawal was substantially greater in monozygotic than in dizygotic twin pairs. Model fitting suggested that twin resemblance for these measures could be ascribed solely to genetic factors, with estimated broad heritabilities of between 35% and 77%.Caffeine is an addictive psychoactive substance. Similar to previous findings with other licit and illicit psychoactive drugs, individual differences in caffeine use, intoxication, tolerance, and withdrawal are substantially influenced by genetic factors.