tbuckley/cabot-search huggingface dataset:
Opening the doors of perception in the irritable bowel syndrome
Authors: LESLEY A HOUGHTON, P J WHORWELL
Journal: Gut (1997)

See article on page505 

It is now nearly 25 years since Ritchie1 first reported that compared with control subjects, patients with irritable bowel syndrome (IBS) exhibit decreased pain thresholds to balloon distension of the pelvic colon. However, the concept that disordered gastrointestinal perception might have a significant pathophysiological role in IBS has only become fashionable during the past decade.

Gastrointestinal sensitivity can be assessed using a number of different stimuli, but the one most commonly used is balloon distension, which can be applied to the gut progressively either in the form of volume or pressure increments (ascending series). The latter involves the use of a barostat which is a computer controlled pump able to inject or withdraw air rapidly from the balloon, thus maintaining a constant pressure irrespective of changes in contractility or tone of the area concerned. In most areas of the gut, a measure of visceral perception is taken as the distension threshold (volume or pressure) to induce discomfort; however, in the rectum, similar thresholds can be obtained for the sensations of gas, call to stool and urgency.

There are a number of technical points that have to be taken into consideration when making comparisons between laboratories. These include whether the distension is applied in a ramp (steady increase), intermittent (returning to baseline between inflations) or stepwise (incremental …
Two-gene control of the expression of a murine Ia antigen.
Authors: P P Jones, D B Murphy, H O McDevitt
Journal: The Journal of Experimental Medicine (1978)

Two dimensional polyacrylamide gel electrophoresis of Non-Idet P-40 extracts and of specific Ia immunoprecipitates from [35S]methionine-labeled mouse spleen lymphocytes has revealed that the cell surface expression of some Ia antigens appears to be controlled by two genes. One locus, which maps in the I-A subregion, is probably the structural gene for an Ia polypeptide chain. The second locus, which maps between the I-J and H-2D regions, controls whether this I-A encoded molecule (Ae) remains in the cytoplasm or is modified and expressed on the cell surface. Complementation between these two loci allowing surface expression of Ae can occur in the cis or trans chromosomal position. Both the I-A molecule and a polypeptide chain coded for by a locus in I-E are coprecipitated by anti-I-E antibodies, suggesting that these two chains are associated with each other as a multisubunit complex in the cell. Because the ability to complement I-A for Ae expression is a property only of those strains which synthesize an I-E-encoded protein, it is likely that the I-E product itself is regulating the expression of Ae. These observations suggest several mechanisms by which interaction between two I region loci can generate new cell surface molecules. As a result, they may have important implications for understanding the molecular basis of two gene control of immune responsiveness and immune suppression.
Systematic analysis of funding awarded for norovirus research to institutions in the United Kingdom, 1997–2010
Authors: Michael G Head, Joseph R Fitchett, Rifat Atun
Journal: Journal of the Royal Society of Medicine (2013)

Objectives Norovirus infections pose great economic and disease burden to health systems around the world. This study quantifies the investments in norovirus research awarded to UK institutions over a 14-year time period. Design A systematic analysis of public and philanthropic infectious disease research investments awarded to UK institutions between 1997 and 2010. Participants None Setting UK institutions carrying out infectious disease research. Main outcome measures Total funding for infectious disease research, total funding for norovirus research, position of norovirus research along the R&amp;D value chain. Results The total dataset consisted of 6165 studies with sum funding of £2.6 billion. Twelve norovirus studies were identified with a total funding of £5.1 million, 0.2% of the total dataset. Of these, eight were categorized as pre-clinical, three as intervention studies and one as implementation research. Median funding was £200,620. Conclusions Research funding for norovirus infections in the UK appears to be unacceptably low, given the burden of disease and disability produced by these infections. There is a clear need for new research initiatives along the R&amp;D value chain: from pre-clinical through to implementation research, including trials to assess cost-effectiveness of infection control policies as well as clinical, public health and environmental interventions in hospitals, congregate settings and in the community.
Criteria air pollutants and toxic air pollutants.
Authors: H H Suh, T Bahadori, J Vallarino, J D Spengler
Journal: Environmental Health Perspectives (2000)

This review presents a brief overview of the health effects and exposures of two criteria pollutants--ozone and particulate matter--and two toxic air pollutants--benzene and formaldehyde. These pollutants were selected from the six criteria pollutants and from the 189 toxic air pollutants on the basis of their prevalence in the United States, their physicochemical behavior, and the magnitude of their potential health threat. The health effects data included in this review primarily include results from epidemiologic studies; however, some findings from animal studies are also discussed when no other information is available. Health effects findings for each pollutant are related in this review to corresponding information about outdoor, indoor, and personal exposures and pollutant sources.
Genome-wide association studies in lung disease: Figure 1
Authors: María Soler Artigas, Louise V Wain, Martin D Tobin
Journal: Thorax (2011)

Genome-wide association studies (GWAS) have provided new insights into the molecular mechanisms of lung function and lung diseases. GWAS, and studies that build upon their findings, will continue to provide evidence aimed at advancing understanding of lung disease. This paper summarises the key features of a GWAS, references some recent findings and discusses how the chest physician can interpret the validity and utility of future GWAS and related studies.
Synovial inflammation does not change in the absence of effective treatment: implications for the use of synovial histopathology as biomarker in early phase clinical trials in rheumatoid arthritis
Authors: D Baeten
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objectives:</b> To determine the impact on synovial histopathology of changes in clinical disease activity in the absence of effective treatment. <b>Methods:</b> Twelve patients with active RA not receiving effective treatment were studied over a 14 week period. Synovial biopsy specimens obtained at baseline and week 14 were analysed by histology and immunohistochemistry. <b>Results:</b> Over the course of 14 weeks, there was a trend towards a decrease of the DAS28, with 7/12 patients being good or moderate DAS28 responders despite the absence of effective treatment. Patients' assessment of global disease activity and swollen joint count both decreased significantly. Histologically, there was a decrease of lining layer hyperplasia and lymphoid aggregates, a similar trend for vascularity, but there was no effect on global synovial infiltration. Accordingly, there was no decrease of the cellular infiltration with T lymphocytes (CD3, CD4, CD8), B lymphocytes (CD20), plasma cells (CD38), dendritic cells (CD1a, CD83), and even an increase of CD163+ sublining macrophages, with a similar trend for CD68+ sublining macrophages. The changes in DAS28 scores in these patients did not correlate with changes in histological variables, with the exception of an inverse correlation with plasma cells. Remarkably, even in the DAS28 responders, no significant changes in synovial inflammatory infiltration were noted. <b>Conclusions:</b> Despite variations in global disease activity, synovial inflammatory infiltration did not change significantly in the absence of effective treatment. The lack of a placebo effect on synovial markers of treatment response such as sublining macrophages can facilitate conclusive early phase trials with small numbers of patients with RA.
Apnoea characteristics across the night in severe obstructive sleep apnoea: influence of body posture
Authors: A. Oksenberg, I. Khamaysi, D.S. Silverberg
Journal: European Respiratory Journal (2001)

Several studies have reported changes in apnoea characteristics across the night in patients with obstructive sleep apnoea (OSA). However, the effect of body posture on these changes has not been evaluated. The purpose of this study was to assess how body posture influences sleep apnoea characteristics across the night in severe OSA. Polysomnograms of 30 patients with severe OSA who had > or = 30 apnoeic episodes in the lateral position and 30 in the supine position during Stage 2 sleep, in the early, middle and late sleep periods were analysed. For each of the 30 events in each body position, the following variables were evaluated: apnoea duration; minimum saturation; change in saturation; duration of arousal; maximum snoring loudness and change in cardiac frequency. Although at any time during the night, apnoeas in the supine posture were more severe than those in the lateral position, a time effect across the night was found only for apnoea duration, change in cardiac frequency and duration of arousal. Body position did not affect the time trend for these variables across the night. The best fit for the changes of these three variables across the night was a quadratic time trend. It was concluded that in severe obstructive sleep apnoea during Stage 2 sleep, body position does not significantly affect the time trends of apnoea characteristics across the night. These data provide support for the participation of sleep-dependent mechanisms (homeostatic and circadian) in the determination of apnoea characteristics across the night.
A novel locus (DSAP2) for disseminated superficial actinic porokeratosis maps to chromosome 15q25.1-26.1
Authors: K. Xia, H. Deng, J.H. Xia, D. Zheng, H.L. Zhang, C.Y. Lu, C.Q. Li, Q. Pan, H.P. Dai, Y.F. Yang, Z.G. Long, H.X. Deng
Journal: British Journal of Dermatology (2002)

Journal Article A novel locus (DSAP2) for disseminated superficial actinic porokeratosis maps to chromosome 15q25.1–26.1 Get access K. Xia, K. Xia National Laboratory of Medical Genetics K.Xia. E‐mail: nlmglcy@xymu.net Search for other works by this author on: Oxford Academic Google Scholar H. Deng, H. Deng National Laboratory of Medical Genetics Search for other works by this author on: Oxford Academic Google Scholar J.H. Xia, J.H. Xia National Laboratory of Medical Genetics Search for other works by this author on: Oxford Academic Google Scholar D. Zheng, D. Zheng National Laboratory of Medical Genetics Search for other works by this author on: Oxford Academic Google Scholar H.L. Zhang, H.L. Zhang National Laboratory of Medical Genetics Search for other works by this author on: Oxford Academic Google Scholar C.Y. Lu, C.Y. Lu National Laboratory of Medical Genetics Search for other works by this author on: Oxford Academic Google Scholar C.Q. Li, C.Q. Li Department of Dermatology, Xiangya Hospital, and Search for other works by this author on: Oxford Academic Google Scholar Q. Pan, Q. Pan National Laboratory of Medical Genetics Search for other works by this author on: Oxford Academic Google Scholar H.P. Dai, H.P. Dai National Laboratory of Medical Genetics Search for other works by this author on: Oxford Academic Google Scholar Y.F. Yang, Y.F. Yang Department of Thoracic Surgery, Xiangya Second Hospital, Central South University, 88 Xiangya Road, Changsha, Hunan 410078, China Search for other works by this author on: Oxford Academic Google Scholar ... Show more Z.G. Long, Z.G. Long National Laboratory of Medical Genetics Search for other works by this author on: Oxford Academic Google Scholar H.X. Deng H.X. Deng National Laboratory of Medical Genetics Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 147, Issue 4, 1 October 2002, Pages 650–654, https://doi.org/10.1046/j.1365-2133.2002.05058.x Published: 01 October 2002 Article history Accepted: 28 July 2002 Published: 01 October 2002
Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial
Authors: Hallvard Holdaas, Bengt Fellström, Alan G Jardine, Ingar Holme, Gudrun Nyberg, Per Fauchald, Carola Grönhagen-Riska, Søren Madsen, Hans-Hellmut Neumayer, Edward Cole, Bart Maes, Patrice Ambuhl, Anders G Olsson, Anders Hartmann, Dag O Solbu, Terje R Pedersen
Journal: The Lancet (2003)
High prevalence of medication use in professional football tournaments including the World Cups between 2002 and 2014: a narrative review with a focus on NSAIDs
Authors: Philippe M Tscholl, Martin Vaso, Alexis Weber, Jiri Dvorak
Journal: British Journal of Sports Medicine (2015)

The use of medication in international football has been monitored since the 2002 FIFA World Cup. Team physicians were asked to provide information on prescribed medication 72 h prior to each match for every player. 69% of adult male players reported using medication, with more than half the players using non-steroidal anti-inflammatory drugs (NSAIDs). Up to one-third of all players used NSAIDs prior to every match, regardless of whether they took the field or not. The mean intake of medication was significantly higher during the FIFA Women's World Cup (0.85 vs 0.77 substances per player and per match in men, p&lt;0.001), whereas the use of NSAIDs was similar to that for men. In the Under-20 and Under-17 male competitions, the use of medication was lower as 60% of players used some kind of medication and 43% of the players used NSAIDs during the tournaments. Despite the potential side effects of medication, especially of NSAIDs in the recovery process after a sports activity, there is no evidence of decreasing intake. The reported incidence is alarming, and moreover is most probably underestimated, since self-medication by the players or treatment already prescribed by club physicians is not included in the published reports. Future studies should focus on the daily dosage, time of treatment and especially the medical indication for painkilling agents to better understand the underlying factors.
PTU-080 Development and Validation of the Crohn’S Life Impact Questionnaire (Cliq)
Authors: J Wilburn, S P McKenna, J Twiss, K Kemp, S Campbell
Journal: Gut (2013)

<h3>Introduction</h3> Crohn's Disease (CD) is a chronic, inflammatory, autoimmune disorder that substantially impairs patients' physical and emotional well-being. Despite this there is no CD-specific patient-reported outcome measure (PROM) available for determining the efficacy of alternative interventions for the condition. The objective of the study is to develop and validate the first such patient-reported outcome measure. Questionnaire content was derived from 30 qualitative interviews conducted with UK CD patients. Cognitive debriefing interviews conducted with a new sample of 15 CD patients indicated that the draught scales were relevant, clear and easy to use. <h3>Methods</h3> A test-retest postal survey was conducted to; identify the final scales, confirm their unidimensionality (by means of Rasch analysis) and to determine reproducibility and construct validity. A subset of the respondents was sent a second questionnaire package 2 weeks after completing the first. The package included the CLIQ, the Nottingham Health Profile (NHP), the Unidimensional Fatigue Impact Scale (U-FIS) and a demographic questionnaire. <h3>Results</h3> The questionnaire package was completed by 273 CD patients (34.4% male; aged 16–79 (mean: 43.9; SD 15.1) years). Of these, 107 also completed the second package. Items were removed from the scales that misfit the Rasch model (Chi2 p &gt; 0.05), were redundant or displayed differential functioning by gender. Rasch analysis confirmed two unidimensional scales (p &lt; 0.05); activity limitations (11 items) and QoL (27 items). Internal consistency was good for both scales (0.93 and 0.91) as was test-retest reliability (0.89 and 0.91 respectively). The CLIQ scales were related (as expected) with the NHP section scores and the U-FIS. It was interesting to note that QoL scores were related to both physical and emotional impairments. <h3>Conclusion</h3> The CLIQ is the first scientifically rigorous PROM designed specifically for CD patients. It consists of two unidimensional scales with excellent psychometric properties. It should prove to be a valuable tool for evaluating the impact of CD and its treatment from the patients' perspective. <h3>Disclosure of Interest</h3> None Declared
Identification of Alternative Splicing Events Regulated by the Oncogenic Factor SRSF1 in Lung Cancer
Authors: Fernando J. de Miguel, Ravi D. Sharma, María J. Pajares, Luis M. Montuenga, Angel Rubio, Ruben Pio
Journal: Cancer Research (2013)

Abnormal alternative splicing has been associated with cancer. Genome-wide microarrays can be used to detect differential splicing events. In this study, we have developed ExonPointer, an algorithm that uses data from exon and junction probes to identify annotated cassette exons. We used the algorithm to profile differential splicing events in lung adenocarcinoma A549 cells after downregulation of the oncogenic serine/arginine-rich splicing factor 1 (SRSF1). Data were generated using two different microarray platforms. The PCR-based validation rate of the top 20 ranked genes was 60% and 100%. Functional enrichment analyses found a substantial number of splicing events in genes related to RNA metabolism. These analyses also identified genes associated with cancer and developmental and hereditary disorders, as well as biologic processes such as cell division, apoptosis, and proliferation. Most of the top 20 ranked genes were validated in other adenocarcinoma and squamous cell lung cancer cells, with validation rates of 80% to 95% and 70% to 75%, respectively. Moreover, the analysis allowed us to identify four genes, ATP11C, IQCB1, TUBD1, and proline-rich coiled-coil 2C (PRRC2C), with a significantly different pattern of alternative splicing in primary non-small cell lung tumors compared with normal lung tissue. In the case of PRRC2C, SRSF1 downregulation led to the skipping of an exon overexpressed in primary lung tumors. Specific siRNA downregulation of the exon-containing variant significantly reduced cell growth. In conclusion, using a novel analytical tool, we have identified new splicing events regulated by the oncogenic splicing factor SRSF1 in lung cancer.
Electrophysiologic and hemodynamic effects of verapamin. Correlation with plasma drug concentrations.
Authors: L M Mangiardi, R J Hariman, R G McAllister, V Bhargava, B Surawicz, R Shabetai
Journal: Circulation (1978)

Verapamil was administered intravenously to 30 open-chest dogs and the electrophysiologic and hemodynamic effects of the drug were correlated with the corresponding plasma concentrations. At concentrations below 152 ng/ml, verapamil prolonged the A-H interval, abolished ventriculoatrial conduction, but did not significantly change sinus rate, cardiac output, left ventricular dp/dt, of systemic vascular resistance. Concentrations above 200 ng/ml were associated with slowing of the sinus rat, high degree atrioventricular block during atrial pacing, 24% decrease in mean aortic pressure, and decreased cardiac output and left ventricular dp/dt. Sinus arrest, high degree atrioventicular block during sinus rhythm, decreased systemic vascular resistance and increased left ventricular end-diastolic pressure occurred when plasma verapamil concentrations exceeded 400 ng/ml. These results show that plasma verapamil concentrations reliably reflect the electrophysiologic and hemodynamic actions of the drug, and that "therapeutic" drug effects can be achieved at plasma concentrations at which myocardial depressant effects are unlikely.
Cost-Utility Analysis of Preoperative Radiotherapy in Patients With Rectal Cancer Undergoing Total Mesorectal Excision: A Study of the Dutch Colorectal Cancer Group
Authors: Mandy van den Brink, Wilbert B. van den Hout, Anne M. Stiggelbout, Elma Klein Kranenbarg, Corrie A.M. Marijnen, Cornelis J.H. van de Velde, Job Kievit
Journal: Journal of Clinical Oncology (2003)

Purpose To compare the societal costs and the (quality-adjusted) life expectancy of patients with rectal cancer undergoing total mesorectal excision (TME) with or without short-term preoperative radiotherapy (5 × 5 Gy). Patients and Methods We used a Markov model to project the clinical and economic outcomes of preoperative radiotherapy. Data on local recurrence rates, quality of life, and costs were obtained from the patients of a multicenter randomized clinical trial. In this trial, 1,861 patients with resectable rectal cancer from 108 hospitals were randomly assigned for TME surgery with or without preoperative radiotherapy. Outcome measures of the model were life expectancy, quality-adjusted life expectancy, lifetime costs per patient, and the incremental cost-effectiveness ratio. Results The base case model estimates that the loss of quality of life due to preoperative radiotherapy is outweighed by the gain in life expectancy. Life expectancy increases by 0.67 years; quality-adjusted life expectancy, by 0.39 years; and costs, by $9,800 per patient. The corresponding cost-effectiveness ratio is $25,100 per quality-adjusted life year. Sensitivity analyses indicate that the cost-effectiveness ratio remains acceptable under a wide range of assumptions. Conclusion Assuming that the reduced local recurrence rate does lead to a survival advantage, the cost-utility analysis estimates that the improved survival outweighs the impaired quality of life and the increased costs. We conclude that short-term preoperative radiotherapy in patients with rectal cancer undergoing TME is both effective and cost-effective.
Effects of chronic heart failure on microvascular oxygen exchange dynamics in muscles of contrasting fiber type
Authors: B Behnke
Journal: Cardiovascular Research (2004)

In rat spinotrapezius muscle, chronic heart failure (CHF) speeds microvascular O2 pressure (pO2; index of O2 delivery-to-O2 uptake) dynamics across the rest-contractions transition [Cardiovasc. Res. 56 (2002) 479]. Due to the mosaic nature of this muscle, the effect of CHF on microvascular pO2 dynamics in different fiber types remains unclear.Based upon derangements of endothelial function and blood flow responses, we hypothesized that CHF would speed microvascular pO2 dynamics (reduced O2 delivery-to-O2 uptake ratio) in type I muscle (soleus, approximately 84% type I), but not in type II muscle (peroneal, approximately 86% type II [J. Appl. Physiol. 80 (1996) 261]).Using phosphorescence quenching, microvascular pO2 was measured at rest and across the rest-contractions transition (1 Hz) in soleus and peroneal of non-infarcted control (control; n=7), and Sprague-Dawley rats with moderate (moderate; elevated left ventricular end-diastolic pressure (LVEDP) 10 +/- 2 mm Hg; n=10) and severe (severe; LVEDP 28 +/- 4 mm Hg; n=5) CHF.The microvascular pO2 mean response time (time delay+time constant) was progressively speeded with increasing severity of CHF in soleus (control, 38.7 +/- 2.0; moderate, 29.1 +/- 1.5; severe, 22.5 +/- 3.9 s; P< or =0.05), but not in peroneal (control=moderate=severe).As type I fibers are recruited predominately for moderate intensity exercise, the more rapid lowering of soleus microvascular pO2 in CHF would reduce the blood-muscle O2 driving gradient, exacerbate phosphocreatine and glycogen breakdown, and provide a mechanism for slowed O2 uptake kinetics and premature fatigue in CHF.