tbuckley/cabot-search huggingface dataset:
Pseudo compartment syndrome of the calf in an athlete secondary to cystic adventitial disease of the popliteal artery: Figure 1
Authors: N Ni Mhuircheartaigh, E Kavanagh, M O’Donohoe, S Eustace
Journal: British Journal of Sports Medicine (2005)

We report a patient with calf pain induced by sport and exercise, initially thought to represent compartment syndrome, in whom MRI and duplex ultrasound ultimately revealed cystic adventitial disease of the popliteal artery. Surgical de-roofing of the popliteal artery resulted in complete resolution of symptoms with return to sporting activities.
Brain Injury in Congenital Heart Disease
Authors: Jane W. Newburger, David C. Bellinger
Journal: Circulation (2006)

ortality rates for virtually all forms of congenital heart disease have declined with dramatic advances in medical, transcatheter, and surgical therapies. 1As the population of congenital heart disease survivors has burgeoned, however, their long-term functional morbidities have become the focus of increasing concern.Among the foremost morbidities are adverse neurodevelopmental outcomes, with their profound personal and societal costs.
Indocyanine green retention test as a noninvasive marker of portal hypertension and esophageal varices in compensated liver cirrhosis
Authors: Andrea Lisotti, Francesco Azzaroli, Federica Buonfiglioli, Marco Montagnani, Paolo Cecinato, Laura Turco, Claudio Calvanese, Patrizia Simoni, Massimo Guardigli, Rosario Arena, Alessandro Cucchetti, Antonio Colecchia, Davide Festi, Rita Golfieri, Giuseppe Mazzella
Journal: Hepatology (2013)

Noninvasive markers would be useful for the assessment of portal hypertension (PH) and esophageal varices (EV) in patients with cirrhosis. The aim of our study was to evaluate the performance of the indocyanine green (ICG) retention test as a noninvasive marker of PH and EV, measured against the gold standards (hepatic venous pressure gradient [HVPG] measurement and upper endoscopy). We prospectively enrolled patients with compensated cirrhosis referral to our unit. All patients underwent laboratory tests, abdominal ultrasound, upper gastrointestinal endoscopy, HVPG measurement, and the ICG 15-minute retention (ICG-r15) test. We evaluated the sensitivity and specificity of the ICG retention test and other noninvasive tools for the diagnosis of PH and EV. Ninety-six consecutive Child-Pugh A patients (67 male and 29 female; 60.3 ± 11.8 years of age) were enrolled. Seventy-four patients had clinically significant portal hypertension (CSPH), of whom 59 had severe portal hypertension (SPH). ICG-r15 and Lok index were independently related to the presence of both CSPH and SPH, whereas ICG-r15 and INR were related to EV. ICG-r15 values (&lt;6.7% and &lt;6.9%, respectively) were able to rule out the presence of CSPH and SPH (LR− 0.15 and 0.14); ICG-r15 &lt;10% provided a 97.8% sensitivity (LR− 0.042) for the exclusion of EV and a 100% sensitivity (LR− 0.0) for large EV. Conclusion : The ICG-r15 test is an effective tool for assessment of PH in patients with compensated cirrhosis. Although this would not replace endoscopy, the ICG-r15 appears able to identify patients with advanced liver disease in which endoscopy is mandatory as well as rule out the presence of EV in patients with compensated cirrhosis. (Hepatology 2014;59:643–650)
MyD88 is critically involved in immune tolerance breakdown at environmental interfaces of Foxp3-deficient mice
Authors: Magali Noval Rivas, Yi T. Koh, Andrew Chen, Annie Nguyen, Young Ho Lee, Greg Lawson, Talal A. Chatila
Journal: Journal of Clinical Investigation (2012)

Tregs expressing the transcription factor Foxp3 suppress self-reactive T cells, prevent autoimmunity, and help contain immune responses to foreign antigens, thereby limiting the potential for inadvertent tissue damage. Mutations in the FOXP3 gene result in Treg deficiency in mice and humans, which leads to the development of a multisystem autoimmune inflammatory disease. The contribution of dysregulated innate immune responses to the pathogenesis of Foxp3 deficiency disease is unknown. In this study, we examined the role of microbial signals in the pathogenesis of Foxp3 deficiency disease by studying Foxp3 mutant mice that had concurrent deficiencies in TLR signaling pathways. Global deficiency of the common TLR adaptor MyD88 offered partial protection from Foxp3 deficiency disease. Specifically, it protected from disease at the environmental interfaces of the skin, lungs, and gut. In contrast, systemic disease, in the form of unrestrained lymphoproliferation, continued unabated. The effect of MyD88 deficiency at environmental interfaces involved the disruption of chemokine gradients that recruit effector T cells and DCs, resulting in their entrapment in secondary lymphoid tissues. These results suggests that Tregs have a key role in maintaining tolerance at host-microbial interfaces by restraining tonic MyD88-dependent proinflammatory signals. Moreover, microbial factors may play a substantial role in the pathogenesis of human autoimmune disease resulting from Treg deficiency.
Phase III Study Comparing Oral Topotecan to Intravenous Docetaxel in Patients With Pretreated Advanced Non–Small-Cell Lung Cancer
Authors: Rodryg Ramlau, Radj Gervais, Maciej Krzakowski, Joachim von Pawel, Eckhard Kaukel, Raymond P. Abratt, Bernie Dharan, Kelly M. Grotzinger, Graham Ross, Graham Dane, Frances A. Shepherd
Journal: Journal of Clinical Oncology (2006)

Purpose This open-label, randomized, multicenter, phase III study compared oral topotecan versus intravenous (IV) docetaxel in patients with previously treated non–small-cell lung cancer (NSCLC). Patients and Methods Patients with stage III or IV NSCLC, performance status ≤ 2, who had received only one prior chemotherapy regimen, were randomly assigned to treatment with oral topotecan 2.3 mg/m 2 /d on days 1 to 5 or IV docetaxel 75 mg/m 2 day 1 every 21 days. Results A total of 829 patients were randomly assigned. In intent-to-treat analysis, 1-year survival rates were 25.1% with topotecan and 28.7% with docetaxel. The difference of −3.6% (95% CI, −9.59% to 2.48%) met the predefined criteria for noninferiority of topotecan relative to docetaxel because the lower limit of the 95% CI was above −10%. Median survival was 27.9 weeks with topotecan and 30.7 weeks with docetaxel. Although not statistically significant (log-rank P = .057), the higher survival rate with docetaxel was maintained across the entire treatment period. The median time to progression was 11.3 weeks with topotecan versus 13.1 weeks with docetaxel (log-rank P = .02). The overall response rate was 5% in each group. Grade 3/4 neutropenia occurred more frequently with docetaxel (60% v 50%). Grade 3/4 anemia and thrombocytopenia occurred more frequently with topotecan (26% v 10% and 26% v 7%, respectively). Conclusion Oral topotecan provides activity in the treatment of relapsed, locally advanced, unresectable NSCLC. Both regimens were well tolerated with differing safety profiles. Topotecan may provide an option for patients who desire an orally available treatment after relapse.
The Mechanics of Ventricular Contraction
Authors: ROBERT F. RUSHMER, NATHAN THAL
Journal: Circulation (1951)

Linear and planimetric measurements have been made on tracings of the right and left ventricular chambers from successive motion picture frames, obtained by cinefluorographic angiocardiography in anesthetized dogs. At the end of systole, varying amounts of residual blood, some 35 per cent of the diastolic volume, remain in the chamber. Filling occurs more rapidly than ventricular ejection and is virtually completed in early diastole. The left ventricular chamber is reduced in size during systole primarily by a reduction in width rather than a shortening of the longitudinal axis. Increased stroke output was accomplished by three mechanisms: (1) increased emptying of the ventricle by progressive shortening of the ventricular chamber; (2) increased filling in early diastole; (3) increased filling in the presystolic period, persumably because the atrial contraction more effectively distended the ventricle. The mechanisms responsible for the systolic residual blood and the retardation of filling which occurs early in diastole are discussed in terms of the anatomy, geometry and functional characteristics of the ventricular myocardium. A comparison is made of the right and left ventricles with reference to their luminal pressure and fiber tension relationships.
Handbook on Obsessive-Compulsive and Related Disordersedited by Katharine A. Phillips, M.D., and Dan J. Stein, M.D., Ph.D. Washington, D.C., American Psychiatric Association Publishing, 2015, 312 pp., $55.00 (paperback).
Authors: Jennifer Lissemore, Thomas E. Nordahl, Chawki Benkelfat
Journal: American Journal of Psychiatry (2015)
Contribution of Preventable Acute Care Spending to Total Spending for High-Cost Medicare Patients
Authors: Karen E. Joynt, Atul A. Gawande, E. John Orav, Ashish K. Jha
Journal: JAMA (2013)

<h3>Importance</h3>A small proportion of patients account for the majority of US health care spending, and understanding patterns of spending among this cohort is critical to reducing health care costs. The degree to which preventable acute care services account for spending among these patients is largely unknown.<h3>Objective</h3>To quantify preventable acute care services among high-cost Medicare patients.<h3>Design, Setting, and Participants</h3>We summed standardized costs for each inpatient and outpatient service contained in standard 5% Medicare files from 2009 and 2010 across the year for each patient in our sample, and defined those in the top decile of spending in 2010 as high-cost patients and those in the top decile in both 2009 and 2010 as persistently high-cost patients. We used standard algorithms to identify potentially preventable emergency department (ED) visits and acute care inpatient hospitalizations. A total of 1 114 469 Medicare fee-for-service beneficiaries aged 65 years or older were included.<h3>Main Outcomes and Measures</h3>Proportion of acute care hospital and ED costs deemed preventable among high-cost patients.<h3>Results</h3>The 10% of Medicare patients in the high-cost group were older, more often male, more often black, and had more comorbid illnesses than non–high-cost patients. In 2010, 32.9% (95% CI, 32.9%-32.9%) of total ED costs were incurred by high-cost patients. Based on validated algorithms, 41.0% (95% CI, 40.9%-41.0%) of these costs among high-cost patients were potentially preventable compared with 42.6% (95% CI, 42.6%-42.6%) among non–high-cost patients. High-cost patients accounted for 79.0% (95% CI, 79.0%-79.0%) of inpatient costs, 9.6% (95% CI, 9.6%-9.6%) of which were due to preventable hospitalizations; 16.8% (95% CI, 16.8%-16.8%) of costs within the non–high-cost group were due to preventable hospitalizations. Comparable proportions of ED spending (43.3%; 95% CI, 43.3%-43.3%) and inpatient spending (13.5%; 95% CI, 13.5%-13.5%) were preventable among persistently high-cost patients. Regions with high primary care physician supply had higher preventable spending for high-cost patients.<h3>Conclusions and Relevance</h3>Among a sample of patients in the top decile of Medicare spending in 2010, only a small percentage of costs appeared to be related to preventable ED visits and hospitalizations. The ability to lower costs for these patients through better outpatient care may be limited.
Imatinib Radiosensitizes Bladder Cancer by Targeting Homologous Recombination
Authors: Boling Qiao, Martin Kerr, Blaz Groselj, Mark T.W. Teo, Margaret A. Knowles, Robert G. Bristow, Roger M. Phillips, Anne E. Kiltie
Journal: Cancer Research (2013)

Radiotherapy is a major treatment modality used to treat muscle-invasive bladder cancer, with patient outcomes similar to surgery. However, radioresistance is a significant factor in treatment failure. Cell-free extracts of muscle-invasive bladder tumors are defective in nonhomologous end-joining (NHEJ), and this phenotype may be used clinically by combining radiotherapy with a radiosensitizing drug that targets homologous recombination, thereby sparing normal tissues with intact NHEJ. The response of the homologous recombination protein RAD51 to radiation is inhibited by the small-molecule tyrosine kinase inhibitor imatinib. Stable RT112 bladder cancer Ku knockdown (Ku80KD) cells were generated using short hairpin RNA technology to mimic the invasive tumor phenotype and also RAD51 knockdown (RAD51KD) cells to show imatinib's pathway selectivity. Ku80KD, RAD51KD, nonsilencing vector control, and parental RT112 cells were treated with radiation in combination with either imatinib or lapatinib, which inhibits NHEJ and cell survival assessed by clonogenic assay. Drug doses were chosen at approximately IC40 and IC10 (nontoxic) levels. Imatinib radiosensitized Ku80KD cells to a greater extent than RAD51KD or RT112 cells. In contrast, lapatinib radiosensitized RAD51KD and RT112 cells but not Ku80KD cells. Taken together, our findings suggest a new application for imatinib in concurrent use with radiotherapy to treat muscle-invasive bladder cancer. Cancer Res; 73(5); 1611-20. ©2012 AACR.
Non-genomic regulation of intermediate conductance potassium channels by aldosterone in human colonic crypt cells
Authors: K A Bowley
Journal: Gut (2003)

<b>Background:</b> Aldosterone has a rapid, non-genomic, inhibitory effect on macroscopic basolateral K<sup>+</sup> conductance in the human colon, reducing its capacity for Cl<sup>−</sup> secretion. The molecular identity of the K<sup>+</sup> channels constituting this aldosterone inhibitable K<sup>+</sup> conductance is unclear. <b>Aim:</b> To characterise the K<sup>+</sup> channel inhibited by aldosterone present in the basolateral membrane of human colonic crypt cells. <b>Methods:</b> Crypts were isolated from biopsies of healthy sigmoid colon obtained during colonoscopy. The effect of aldosterone on basolateral K<sup>+</sup> channels, and the possible involvement of Na<sup>+</sup>:H<sup>+</sup> exchange, were studied by patch clamp techniques. Total RNA from isolated crypts was subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) using primers specific to intermediate conductance K<sup>+</sup> channels (KCNN4) previously identified in other human tissues. <b>Results:</b> In cell attached patches, 1 nmol/l aldosterone significantly decreased the activity of intermediate conductance (27 pS) K<sup>+</sup> channels by 31%, 53%, and 54% after 1, 5 and 10, minutes, respectively. Increasing aldosterone concentration to 10 nmol/l produced a further 56% decrease in channel activity after five minutes. Aldosterone 1–10 nmol/l had no effect on channel activity in the presence of 20 μmol/l ethylisopropylamiloride, an inhibitor of Na<sup>+</sup>:H<sup>+</sup> exchange. RT-PCR identified <i>KCNN4</i> mRNA, which is likely to encode the 27 pS K<sup>+</sup> channel inhibited by aldosterone. <b>Conclusion:</b> Intermediate conductance K<sup>+</sup> channels (KCNN4) present in the basolateral membranes of human colonic crypt cells are a target for the non-genomic inhibitory effect of aldosterone, which involves stimulation of Na<sup>+</sup>:H<sup>+</sup> exchange, thereby reducing the capacity of the colon for Cl<sup>−</sup> secretion.
The importance of listening: engaging and incorporating the athlete's voice in theory and practice
Authors: J R Weissensteiner
Journal: British Journal of Sports Medicine (2015)

The ‘voice’ or perspective of the athlete is commonly unheard in research and practice relating to athlete development. This is seemingly ironic, given that ‘the athlete’ is purportedly the central focus and they have lived the experience, making them a truly qualified ‘knowledge expert’.

Gary Hall Jr, a five-time Olympic gold medallist and advocate, started proceedings at the recent IOC Consensus meeting on youth athlete development in sport by reflecting on his experiences as an athlete. What he shared was insightful and compelling. As the meeting progressed, invited experts voiced their shared concern regarding issues relating to athletes’ welfare, well-being and development, including depressive illness, burnout, role strain, eating disorders, injury, bullying and harassment. It was recognised that a concerted research and coordinated support effort must be taken to further understand and address these issues. Central to achieving this, effective engagement of the perspective of the athlete is critical.

It is well accepted within the contemporary literature that an athlete's performance, at each stage of …
Differential expression of IL-33 and HMGB1 in the lungs of stable cystic fibrosis patients
Authors: Kerstin Tiringer, Angela Treis, Stefan Kanolzer, Carina Witt, Bahil Ghanim, Saskia Gruber, Klara Schmidthaler, Sabine Renner, Eleonora Dehlink, Edith Nachbaur, Thomas Frischer, Walter Klepetko, Cezmi A Akdis, Zsolt Szépfalusi, Thomas Eiwegger
Journal: European Respiratory Journal (2014)

To the Editor: 

In cystic fibrosis (CF), repeated inflammation of the lung leads to progressive damage of lung tissue [1, 2]. In case of tissue destruction or in response to inflammation, necrotic cells release danger signals. These proteins trigger inflammatory responses, contribute to elimination of pathogens and induce tissue repair [3]. Imbalanced or uncontrolled release of such mediators may amplify inflammatory responses that in turn facilitate tissue damage.

Interleukin (IL)-33 and high-mobility group box 1 protein (HMGB1) are both considered to be such “alarmins” [3]. Given the T-helper cell (Th)17/Th2 nature of lung inflammation in asymptomatic CF individuals and its linkage to CF-associated pathogens [1, 2], we hypothesised that IL-33 and HMGB1 may contribute to the local sustained inflammatory processes.

Both these alarmins are dual-function proteins, as they are nuclear factors regulating gene expression and also act as cytokines when released from cells [3]. In contrast to ubiquitously expressed HMGB1, IL-33 is mainly expressed in barrier-function-like epithelial cells [3]. IL-33 is mainly linked to augmentation and initiation of Th2-type inflammation but might also antagonise overwhelming tissue inflammation linked to pathogens [4–6]. HMGB1 acts as a cytokine, which contributes to activation of innate receptors, matures dendritic cells (DCs), contributes to migration of DCs and amplifies inflammation itself via induction of pro-inflammatory cytokines like tumour necrosis factor (TNF)-α, IL-6, IL-1β and macrophage inflammatory protein (MIP)1 [7].

To directly compare the contributions of released IL-33 and HMGB1 in CF lung inflammation, we assessed protein levels in bronchoalveolar lavage fluid (BALF) of 44 CF patients and 10 non-CF controls with recurrent pulmonary infections. To increase the homogeneity of the CF population, patients with …
Multiscale requirements for bioencapsulation in medicine and biotechnology
Authors: Paul de Vos, Marek Bucko, Peter Gemeiner, Marian Navratil, Juraj Svitel, Marijke Faas, Berit Lokensgard Strand, Gudmund Skjak-Braek, Yrr A. Morch, Alica Vikartovska, Igor Lacik, Gabriela Kollarikova, Gorka Orive, Dennis Poncelet, Jose Luis Pedraz, Marion B. Ansorge-Schumacher
Journal: Biomaterials (2009)
Instability of Foxp3 Expression Limits the Ability of Induced Regulatory T Cells to Mitigate Graft versus Host Disease
Authors: Amy Beres, Richard Komorowski, Masahiko Mihara, William R. Drobyski
Journal: Clinical Cancer Research (2011)

Graft versus host disease (GVHD) is the major complication of allogeneic bone marrow transplantation (BMT) and limits the therapeutic efficacy of this modality. Although the role of natural T-regulatory cells (nTreg) in attenuating GVHD has been extensively examined, the ability of induced T-regulatory cells (iTreg) to mitigate GVHD is unknown. The purpose of this study was to examine the ability of in vitro and in vivo iTregs to abrogate GVHD.We examined the ability of in vitro differentiated and in vivo iTregs to reduce the severity of GVHD in a clinically relevant mouse model of BMT. The effect of blockade of interleukin (IL) 6 signaling on the efficacy of these Treg populations was also studied.In vitro differentiated iTregs fail to protect mice from lethal GVHD even when administered at high Treg:effector T-cell ratios. Lack of GVHD protection was associated with loss of Foxp3 expression and in vivo reversion of these cells to a proinflammatory phenotype characterized by secretion of IFN-γ. Phenotypic reversion could not be abrogated by blockade of IL-6 signaling or by in vitro exposure of iTregs to all-trans retinoic acid. In contrast, the in vivo induction of iTregs was significantly augmented by IL-6 blockade and this resulted in reduced GVHD.Instability of Foxp3 expression limits the utility of adoptively transferred iTregs as a source of cellular therapy for the abrogation of GVHD. Blockade of IL-6 signaling augments the ability of in vivo iTregs to prevent GVHD but has no effect on in vitro differentiated iTregs.
Utility of animal models for identification of potential therapeutics for rheumatoid arthritis
Authors: M Hegen, J C Keith, M Collins, C L Nickerson-Nutter
Journal: Annals of the Rheumatic Diseases (2007)

Animal models of rheumatoid arthritis (RA) are widely used for testing potential new therapies for RA. However, the question of which animal model is most predictive of therapeutic efficacy in human RA commonly arises in data evaluation. A retrospective review of the animal models used to evaluate approved, pending RA therapies, and compounds that were discontinued during phase II or III clinical trials found that the three most commonly used models were adjuvant-induced arthritis (AIA) in rats and collagen-induced arthritis (CIA) in rats and mice. Limited data were found for more recently developed genetically modified animal models. Examination of the efficacy of various compounds in these animal models revealed that a compound's therapeutic efficacy, rather than prophylactic efficacy, in AIA and CIA models was more predictive of clinical efficacy in human RA than data from either model alone.
Differences in Vascular Bed Disease Susceptibility Reflect Differences in Gene Expression Response to Atherogenic Stimuli
Authors: David Xing-Fei Deng, Anya Tsalenko, Aditya Vailaya, Amir Ben-Dor, Ramendra Kundu, Ivette Estay, Raymond Tabibiazar, Robert Kincaid, Zohar Yakhini, Laurakay Bruhn, Thomas Quertermous
Journal: Circulation Research (2005)

Atherosclerosis occurs predominantly in arteries and only rarely in veins. The goal of this study was to test whether differences in the molecular responses of venous and arterial endothelial cells (ECs) to atherosclerotic stimuli might contribute to vascular bed differences in susceptibility to atherosclerosis. We compared gene expression profiles of primary cultured ECs from human saphenous vein (SVEC) and coronary artery (CAEC) exposed to atherogenic stimuli. In addition to identifying differentially expressed genes, we applied statistical analysis of gene ontology and pathway annotation terms to identify signaling differences related to cell type and stimulus. Differential gene expression of untreated venous and arterial endothelial cells yielded 285 genes more highly expressed in untreated SVEC (P<0.005 and fold change >1.5). These genes represented various atherosclerosis-related pathways including responses to proliferation, oxidoreductase activity, antiinflammatory responses, cell growth, and hemostasis functions. Moreover, stimulation with oxidized LDL induced dramatically greater gene expression responses in CAEC compared with SVEC, relating to adhesion, proliferation, and apoptosis pathways. In contrast, interleukin 1beta and tumor necrosis factor alpha activated similar gene expression responses in both CAEC and SVEC. The differences in functional response and gene expression were further validated by an in vitro proliferation assay and in vivo immunostaining of alphabeta-crystallin protein. Our results strongly suggest that different inherent gene expression programs in arterial versus venous endothelial cells contribute to differences in atherosclerotic disease susceptibility.