tbuckley/cabot-search huggingface dataset:
Kidney Transplantation from Donors without a Heartbeat
Authors: Markus Weber, Daniel Dindo, Nicholas Demartines, Patrice M. Ambühl, Pierre-Alain Clavien
Journal: New England Journal of Medicine (2002)

The dramatic shortage of kidney donors has triggered interest in other sources of organs, such as donors without a heartbeat. Accumulating evidence suggests that the short-term survival of cadaveric kidneys from such donors is similar to that of cadaveric kidneys from donors with a heartbeat. However, no data from large, matched studies with long-term follow-up are available. We conducted a matched, single-center study of kidney transplants obtained from donors without a heartbeat and those from donors with a heartbeat, with a 15-year follow-up period.Between 1985 and 2000, 122 kidney transplantations involving donors without a heartbeat were performed at the University of Zurich, in Switzerland. Outcomes of these procedures were compared with those of 122 transplantations of kidneys from donors with a heartbeat. The recipients were matched according to age, sex, number of transplantations, and calendar period of transplantation.The characteristics of the recipients did not differ significantly between the two groups. We observed a significantly higher incidence of delayed graft function among the patients who received kidneys from donors without a heartbeat (48.4 percent) than among the patients who received kidneys from donors with a heartbeat (23.8 percent) (P<0.001). However, the long-term rate of graft survival was similar in the two groups (P=0.98): at 10 years, the rate of graft survival was 78.7 percent for kidneys from donors without a heartbeat and 76.7 percent for kidneys from donors with a heartbeat.Although the incidence of delayed graft function is significantly higher with kidneys from donors without a heartbeat than with kidneys from donors with a heartbeat, there is no difference in long-term outcome between the two types of graft.
Drugs and Exposure Treatment in Phobic and Obsessive-Compulsive Disorders
Authors: Isaac Marks
Journal: Journal of the Royal Society of Medicine (1984)

Several classes of drugs have been used with behavioural treatments in phobic and obsessive-compulsive disorders (Marks 1981). Sedatives like barbiturates, benzodiazepines and alcohol have not been found to be of lasting benefit and in high doses may actually be counterproductive because what is learned under the influence of the drug usually fails to transfer to the drug-free state. Beta-blockers too have not had durable effects. Antidepressants seem to be of greater value.
Is aortic dilatation an atherosclerosis-related process?
Authors: Yoram Agmon, Bijoy K Khandheria, Irene Meissner, Gary L Schwartz, JoRean D Sicks, Angela J Fought, W.Michael O'Fallon, David O Wiebers, A.Jamil Tajik
Journal: Journal of the American College of Cardiology (2003)
P106 Inflammatory markers: data from the UK CF Gene Therapy Consortium Run-In Study
Authors: J. A. Innes, J. Donovan, S. Soussi, N. Newman, J. Leiton, K. Campbell, J. Gibson, A. Doherty, E. W. F. W. Alton, C. Boyd, U. Griesenbach, J. C. Davies
Journal: Thorax (2010)

<h3></h3> Inflammatory markers in sputum and serum have been used with variable success as outcome measures in interventional studies. Limited data are available on reproducibility of such assays in cystic fibrosis (CF) particularly over a long time period. This study was designed to address this; stable patients (FEV<sub>1</sub>&gt;40, &gt;10 years age) were recruited into the study which ran over an 18-month period with up to four hospital visits. Patients provided a 24 h sputum collection, for weighing at each visit. Spontaneous sputum was collected at the beginning of each visit; if insufficient sample was obtained, sputum was induced with hypertonic saline. Inflammatory markers were measured in dithiothreitol-processed sputum (total and differential cell counts, IL8 (and other cytokines), calprotectin, neutrophil elastase, myeloperoxidase and extracellular DNA). Blood was collected at each visit for cytokines (IL1β, IL6, IL8, IL10, IL12 (p40) and TNFα) and calprotectin. Data are available from 189 patients at 655 visits. Adequate sputum for analysis was obtained at only 60% of visits. Sputum induction accounted for only 16% of adequate samples. Median and range for each detectable assay are shown below. Serum cytokines IL1β, IL10, IL12 (p40) and TNFα were undetectable at each visit, and IL6 was only detectable in 17% of samples. To assess intra-individual variability the coefficient of variation of results across each visit for each patient is presented. Both sputum and serum assays showed a large range of results at each visit, but the variation for each individual was much higher than the ideal 10%. Serum assays were not able to discriminate between CF and non-CF, apart from calprotectin (CF 10.1(0.8–72.5) vs non-CF 0.40 (0.2–1.12) p&lt;0.001). Due to the difficulty in obtaining sputum samples reliably and the large variability of results between visits in these stable patients, we consider it unlikely that a change due to a new therapy would be detectable. As such, we are not considering sputum inflammatory markers as primary or secondary efficacy endpoints in our multidose gene therapy trial. Serum markers also appear to be of limited use is assessing efficacy but will still be useful for toxicology and safety studies.
A Method For Assessing Regional Determinants Of Eosinophilia In Chronic Rhinosinusitis
Authors: Bruce K. Tan, Erin Rocci, Kent Lam, He Huang, Lydia Suh, Avesh Thuluvath, Alcina K. Lidder, Rakesh Chandra, David Conley, Stephanie Shintani-Smith, Kathryn E. Hulse, Atsushi Kato, Anju T. Peters, Leslie C. Grammer, Robert C. Kern, Robert P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2014)
Romidepsin and Belinostat Synergize the Antineoplastic Effect of Bortezomib in Mantle Cell Lymphoma
Authors: Luca Paoluzzi, Luigi Scotto, Enrica Marchi, Jasmine Zain, Venkatraman E. Seshan, Owen A. O'Connor
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Romidepsin and belinostat are inhibitors of histone deacetylases (HDACI). HDACIs are known to induce cell death in malignant cells through multiple mechanisms, including upregulation of death receptors and induction of cell cycle arrest. They are also known to be prodifferentiating. Mantle cell lymphoma (MCL) is an aggressive subtype of non–Hodgkin lymphoma characterized by the t(11;14)(q13;q32) translocation leading to the overexpression of cyclin D1. Experimental Design: Assays for cytotoxicty including mathematical analysis for synergism, flow-cytometry, immunoblottings, and a xenograft severe combined immunodeficient beige mouse model were used to explore the in vitro and in vivo activity of romidepsin and/or belinostat alone or in combination with the proteasome inhibitor bortezomib in MCL. Results: In vitro, romidepsin and belinostat exhibited concentration-dependent cytotoxicity against a panel of MCL cell lines. Both HDACI showed strong synergism when combined with the proteasome inhibitor bortezomib in MCL. An HDACI plus bortezomib also induced potent mitochondrial membrane depolarization and apoptosis, whereas no significant apoptosis was observed in peripheral blood mononuclear cells from healthy donors with the combination. These events were associated with a decrease in cyclin D1 and Bcl-XL, and an increase in accumulation of acetylated histone H3, acetylated α-tubulin, and Noxa in cell lines. In a severe combined immunodeficient beige mouse model of MCL, the addition of belinostat to bortezomib enhanced efficacy compared with either drug alone. Conclusions: Collectively, these data strongly suggest that HDACI such as romidepsin or belinostat in combination with a proteasome inhibitor could represent a novel and rationale platform for the treatment of MCL. Clin Cancer Res; 16(2); 554–65
TCT-55 Has PRAMI Changed Practice? An International Survey of Approaches to the Management of Non-Culprit Lesions in Patients Undergoing Primary Percutaneous Coronary Intervention (PCI) for ST-Elevation Myocardial Infarction (STEMI)
Authors: Novalia Purnama Sidik, Colin Berry, ERIC EECKHOUT, Eilidh McGinnigle, James T. Stewart, Keith G. Oldroyd
Journal: Journal of the American College of Cardiology (2014)
Portioning out the contribution of dead space ventilation and low CO2 set point to ventilatory inefficiency during exercise in chronic thromboembolic pulmonary hypertension
Authors: Roberta Pulcheri Ramos, Jaquelina Sonoe Ota Arakaki, Eloara Vieira Machado Ferreira, Adriano Acedo, Melline Almeida, Luiz Eduardo Nery, J. Alberto Neder
Journal: European Respiratory Journal (2012)

Rationale : The individual relevance of enlarged dead space ventilation as a fraction of tidal volume (VD/VT) and low CO 2  set-point in promoting exercise ventilatory inefficiency in chronic thromboembolic pulmonary hypertension (CTEPH) remains controversial.  Objective : To determine the contributing role of VD/VT and PaCO 2  on the excessive ventilatory response to exercise in patients with CTEPH.  Material and methods : 20 patients (47 ± 14 yrs, mean pulmonary artery pressure= 52 ± 10 mmHg) underwent an incremental exercise test and a steady-state test with arterial blood gases measurements.  Results:  Compared to normal standards, patients showed lower resting PaCO 2  and peak V9O 2  but greater ΔV9E/ΔV9CO 2  slope (68 ± 16). Peak V9O 2  and ΔV9E/ΔV9CO 2  were inversely correlated (r= -0.70; p 2  ratio during the constant work rate test was also abnormally high (62 ± 15). VD/VT increased from 0.31±0.08 at rest to 0.39±0.11 during exercise; on the other hand, end-tidal partial pressure (PET) for CO 2  decreased despite a stable PaCO 2  (p>0.05). Consequently, P(a-ET)CO 2  became wider (4 ± 3 mmHg to 8 ± 5 mmHg), a finding related to greater V9E/V9CO 2  (r= 0.81; p 2  (partial r = -0.37) explained up to 90% of V9E/V9CO 2  variability (125.9 VD/VT - 2.3 PaCO 2  + 77.1; p Conclusion:  Increased VD/VT is the main pathophysiological mechanism leading to an excessive ventilatory response to exercise in patients with CTEPH. Low CO 2  set-point responds for a relatively minor portion of this abnormal feature.
Bile reflux gastritis and Barrett's oesophagus: further evidence of a role for duodenogastro-oesophageal reflux?
Authors: M F Dixon
Journal: Gut (2001)

<h3>BACKGROUND</h3> There is increasing evidence that reflux of bile plays a part in the pathogenesis of Barrett9s oesophagus. Bile injury to the gastric mucosa results in a “chemical” gastritis in which oedema and intestinal metaplasia are prominent. <h3>AIM</h3> To determine if patients with Barrett9s oesophagus have more bile related changes in antral mucosa than patients with uncomplicated gastro-oesophageal reflux disease (GORD) or non-ulcer dyspepsia (NUD). <h3>PATIENTS AND METHODS</h3> Patients were identified by a retrospective search of pathology records and those with a clinically confirmed diagnosis of either Barrett9s oesophagus or reflux oesophagitis who had oesophageal and gastric biopsies taken at the same endoscopy and had no evidence of <i>Helicobacter pylori</i> infection entered the study. Control biopsies were taken from <i>H pylori </i>negative NUD patients. Antral biopsies were examined “blind” to clinical group and graded for a series of histological features from which the “reflux gastritis score” (RGS) and “bile reflux index” (BRI) could be calculated. The reproducibility of these histological scores was tested by a second pathologist. <h3>RESULTS</h3> There were 100 patients with Barrett9s, 61 with GORD, and 50 with NUD. The RGSs did not differ between groups. BRI values in the Barrett9s group were significantly higher than those in GORD subjects (p=0.014) which in turn were higher than those in NUD patients (p=0.037). Similarly, the frequency of high BRI values (&gt;14) was significantly greater in the Barrett9s group (29/100; 29%) than in the GORD (9/61; 14.8%) or NUD (4/50; 8%) group. However, agreement on BRI values was “poor”, indicating limited applicability of this approach. <h3>CONCLUSION</h3> Patients with Barrett9s oesophagus have more evidence of bile related gastritis than subjects with uncomplicated GORD or NUD. The presence of bile in the refluxate could be a factor in both the development of “specialised” intestinal metaplasia and malignancy in the oesophagus.
Do H2 receptor antagonists have to be given at night? A study of the antisecretory profile of SKF 94482, a new H2 receptor antagonist which has a profound effect on daytime acidity.
Authors: S G Chiverton, D W Burget, R H Hunt
Journal: Gut (1989)

Evening dosing has become standard for H2 receptor antagonists, because available agents inhibit nocturnal basal acid secretion more effectively than daytime stimulated secretion. We studied the optimal time of administration of a new high affinity long acting H2 receptor antagonist, SKF 94482, for the suppression of intragastric acidity using intragastric telemetry. Sixteen healthy subjects received SKF 94482 200 mg or placebo at 07:30, 17:30, and 21:30 h during four separate studies. Time (h) above pH 4 was (mean (SD] 1.1 (1.2) on placebo, 7.8 (5.0) on SKF 94482 given at 07:30, 5.75 (3.6) on SKF 94482 given at 17:30, and 6.1 (2.9) when given at 21:30. All treatment regimens were effective in increasing time above pH 4 (p less than 0.01). The efficacy of the morning dose of SKF 94482 indicates that the best time to give H2 receptor antagonists depends on their pharmacological properties.
Higher Cortical and Lower Subcortical Metabolism in Detoxified Methamphetamine Abusers
Authors: N D Volkow, L Chang, G J Wang, J S Fowler, D Franceschi, M J Sedler, S J Gatley, R Hitzemann, Y S Ding, C Wong, J Logan
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Methamphetamine has raised concerns because it may be neurotoxic to the human brain. Although prior work has focused primarily on the effects of methamphetamine on dopamine cells, there is evidence that other neuronal types are affected. The authors measured regional brain glucose metabolism, which serves as a marker of brain function, to assess if there is evidence of functional changes in methamphetamine abusers in regions other than those innervated by dopamine cells. METHOD: Fifteen detoxified methamphetamine abusers and 21 comparison subjects underwent positron emission tomography following administration of [18F]fluorodeoxyglucose. RESULTS: Whole brain metabolism in the methamphetamine abusers was 14% higher than that of comparison subjects; the differences were most accentuated in the parietal cortex (20%). After normalization for whole brain metabolism, methamphetamine abusers exhibited significantly lower metabolism in the thalamus (17% difference) and striatum (where the differences were larger for the caudate [12%] than for the putamen [6%]). Statistical parametric mapping analyses corroborated these findings, revealing higher metabolism in the parietal cortex and lower metabolism in the thalamus and striatum of methamphetamine abusers. CONCLUSIONS: The fact that the parietal cortex is a region devoid of any significant dopaminergic innervation suggests that the higher metabolism seen in this region in the methamphetamine abusers is the result of methamphetamine effects in circuits other than those modulated by dopamine. In addition, the lower metabolism in the striatum and thalamus (major outputs of dopamine signals into the cortex) is likely to reflect the functional consequence of methamphetamine in dopaminergic circuits. These results provide evidence that, in humans, methamphetamine abuse results in changes in function of dopamine- and nondopamine-innervated brain regions.
P130 Living with Idiopathic Pulmonary Fibrosis: Results of a European Patient Survey
Authors: C Giot, K Kirchgassler, M Maronati
Journal: Thorax (2012)

<h3>Introduction and Objectives</h3> Idiopathic pulmonary fibrosis (IPF) is a rare, fibrotic, progressive lung disease that results in shortness of breath and difficulty in breathing. IPF commonly presents with crackling sounds in the lungs discernable via stethoscopic auscultation. IPF is most prevalent in patients &gt;50 years of age. Risk factors include smoking and environmental exposures (metal, wood dust and other airborne pollutants). Disease progression features clubbing of the fingers, increasing difficulty in breathing, requirement for supplemental oxygen and/or lung transplantation. IPF is ultimately fatal. We conducted a European survey of diagnosed IPF patients to identify unmet needs in the management of IPF and opportunities to improve care. <h3>Methods</h3> Patients in Germany, France, Italy, Spain and the UK with a confirmed diagnosis of IPF underwent a structured interview at home. In some instances, involved carers were also interviewed. The interviews featured associative questions where images were selected to express feelings, and constructive questions where factual recall was tested. Patient emotions were mapped according to four principle stages of the patient journey: 1. Symptoms, 2. Initial diagnosis, 3. After diagnosis, and 4. Disease management. <h3>Results</h3> Forty-five patients (median age 67 years) and 18 care givers were interviewed for the survey. In 58% of cases, diagnosis was protracted due to dismissal of symptoms and misdiagnosis. Patients could be categorised in one of four ways (combative, serene, dejected and stoic) based chiefly on their age and attitude to disease management. Patients expressed a range of emotions at the point of diagnosis, and diagnosis was recognised as a time at which the patient-doctor relationship could break down. Patients treated in specialist centres reported better satisfaction with care than those treated by generalists. The patients cited negative impacts of IPF on almost all aspects of their lives, which could lead to depression. Keeping fit was acknowledged as a means to control disease symptoms and maintain a positive outlook. <h3>Conclusion</h3> IPF has an enormous impact on patient quality of life, and patients are affected differently by the disease and its diagnosis. Emotional support and participation in patient support groups should be considered a key component of IPF management.
There is a ‘uc’ in mucus, but is there mucus in UC?
Authors: Michael A McGuckin, Sumaira Z Hasnain
Journal: Gut (2013)

All mucosal surfaces are covered by a layer of mucus which hydrates, lubricates and protects the underlying epithelium. Endoscopists will be highly familiar with the shiny mucus layer covering the intestine. However, because of its intrinsic properties, particularly its high water content, mucus is difficult to preserve and measure, is lost in standard histological processing and is often overlooked in studies of intestinal pathophysiology.

The major macromolecular constituents of mucus are secreted mucin glycoproteins, and in the normal intestine this is, almost exclusively, MUC2. MUC2 is synthesised in intestinal goblet cells and packed into granules as large disulfide linked polymers. These granules form the distinctive goblet shaped thecae which is the defining morphological feature of goblet cells. On release and hydration, the mucin polymers swell 100–1000-fold, forming the viscous mucus barrier. While the mucins are largely responsible for the properties of mucus, mucus contains many other proteins, including antimicrobial molecules and antibodies. In the rodent colon, the mucus layer is around 700 µm thick, with an inner difficult to dislodge layer and an outer layer that is looser and easier to displace. Gunnar Hansson's group, from the University of Gothenburg, have previously shown that the inner mucus layer is devoid of microbes, effectively separating the luminal microbes from the epithelial cells.1 …
A FURTHER STUDY OF SOME FEATURES OF THE INTERVIEW WITH THE INTERACTION CHRONOGRAPH
Authors: VICENTE B. TUASON, SAMUEL B. GUZE, JAMES MCCLURE, JERRY BEGUELIN
Journal: American Journal of Psychiatry (1961)

A brief review of the concepts and methods involved in the objective description and measurement of "personality" by means of interaction chronograph methods, together with a comment on previous studies, have been presented. The present study was concerned with testing the reliability of lO-min. and 30-min. samples of Period I type behavior, following the rules of a partially standardized interview. Using interaction chronograph measures, it was concluded that 10 min. are sufficient to reach a stable pattern of patient communication under Period I conditions. It was established further that extending the period of observation to 30 min. offers a much more stabilized interaction.
A conserved human T cell population targets mycobacterial antigens presented by CD1b
Authors: Ildiko Van Rhijn, Anne Kasmar, Annemieke de Jong, Stephanie Gras, Mugdha Bhati, Marieke E Doorenspleet, Niek de Vries, Dale I Godfrey, John D Altman, Wilco de Jager, Jamie Rossjohn, D Branch Moody
Journal: Nature Immunology (2013)
Tuberculosis treatment effect on T-cell interferon- responses to Mycobacterium tuberculosis-specific antigens
Authors: C.B.E. Chee, K.W. Khinmar, S.H. Gan, T.M. Barkham, C.K. Koh, L. Shen, Y.T. Wang
Journal: European Respiratory Journal (2009)

The hypothesis that T-cell interferon-γ responses to Mycobacterium tuberculosis- specific antigens decline as disease activity diminishes with tuberculosis (TB) treatment has generated interest in the interferon-γ release assays (IGRAs) as treatment-monitoring tools. We studied the effect of TB treatment on these responses as measured by the QuantiFERON-TB® Gold In-tube (QFT-IT) and T-SPOT. TB ® assays. 275 sputum culture-positive, HIV-uninfected pulmonary TB patients were tested with QFT-IT and T-SPOT. TB ® at baseline, treatment completion and 6 months thereafter. The QFT-IT was also performed at the end of the intensive phase. The time-treatment effect on the qualitative and quantitative IGRA results was determined. There were significant declines in the positivity rates and quantitative results of both IGRAs with treatment. The QFT-IT positivity rate was significantly lower than the T-SPOT. TB ®. The test reversion rate was significantly different for the two assays (13.9% for T-SPOT. TB ® versus 39.2% for QFT-IT). 79% and 46% tested positive with T-SPOT. TB ® and QFT-IT respectively at 6 months post-treatment completion. The kinetics of the quantitative responses was not significantly different between subjects with and without risk factors for disease relapse. That a substantial proportion of patients remained test-positive after TB treatment would suggest a limited role of IGRAs as treatment monitoring tools.