tbuckley/cabot-search huggingface dataset:
Oxyhemoglobin-Induced Suppression of Voltage-Dependent K <sup>+</sup> Channels in Cerebral Arteries by Enhanced Tyrosine Kinase Activity
Authors: Masanori Ishiguro, Anthony D. Morielli, Katarina Zvarova, Bruce I. Tranmer, Paul L. Penar, George C. Wellman
Journal: Circulation Research (2006)

Cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) has devastating consequences. Oxyhemoglobin (oxyhb) has been implicated in SAH-induced cerebral vasospasm as it causes cerebral artery constriction and increases tyrosine kinase activity. Voltage-dependent, Ca(2+)-selective and K(+)-selective ion channels play an important role in the regulation of cerebral artery diameter and represent potential targets of oxyhb. Here we provide novel evidence that oxyhb selectively decreases 4-aminopyridine sensitive, voltage-dependent K(+) channel (K(v)) currents by approximately 30% in myocytes isolated from rabbit cerebral arteries but did not directly alter the activity of voltage-dependent Ca(2+) channels or large conductance Ca(2+)-activated (BK) channels. A combination of tyrosine kinase inhibitors (tyrphostin AG1478, tyrphostin A23, tyrphostin A25, genistein) abolished both oxyhb-induced suppression of K(v) channel currents and oxyhb-induced constriction of isolated cerebral arteries. The K(v) channel blocker 4-aminopyridine also inhibited oxyhb-induced cerebral artery constriction. The observed oxyhb-induced decrease in K(v) channel activity could represent either channel block, or a decrease in K(v) channel density on the plasma membrane. To explore whether oxyhb altered trafficking of K(v) channels to the plasma membrane, we used an antibody generated against an extracellular epitope of K(v)1.5 channels. In the presence of oxyhb, staining of K(v)1.5 on the plasma membrane surface was markedly reduced. Furthermore, oxyhb caused a loss of spatial distinction between staining with K(v)1.5 and the general anti-phosphotyrosine antibody PY-102. We propose that oxyhb-induced suppression of K(v) currents occurs via a mechanism involving enhanced tyrosine kinase activity and channel endocytosis. This novel mechanism may contribute to oxyhb-induced cerebral artery constriction following SAH.
Advances in the identification and analysis of allele-specific expression
Authors: Christopher G Bell, Stephan Beck
Journal: Genome Medicine (2009)

Allele-specific expression (ASE) is essential for normal development and many cellular processes but, if impaired, can result in disease. ASE is a feature of organisms with genomes consisting of more than one set of homologous chromosomes. The higher the number of chromosome sets (ploidy) per cell, the higher the potential complexity of ASE. Humans, for instance, are diploid (except germ cells, which are haploid), resulting in multiple possible expression states in time and space for each set of alleles. ASE is invoked and modulated by both genetic and epigenetic changes, affecting the underlying DNA sequence or chromatin of each allele, respectively. Although numerous methods have been developed to assay ASE, they usually require RNA to be available and are dependent upon genetic polymorphisms (such as single nucleotide polymorphisms (SNPs)) to differentiate between allelic transcripts. The rapid convergence to second-generation sequencing as the method of choice to examine genomic, epigenomic and transcriptomic data enables an integrated and more general approach to define and predict ASE, independent of SNPs. This 'Omni-Seq' approach has the potential to advance our understanding of the biology and pathophysiology of ASE-mediated processes by elucidating subtle combinatorial effects, leading to the accurate delineation of sub-phenotypes with consequential benefit for improved insight into disease etiology.
Management of a Patient With Advanced<i>BRAF</i>-Mutant Melanoma
Authors: Michelle T. Ashworth, Adil Daud
Journal: Journal of the National Comprehensive Cancer Network (2014)

A 49-year-old man initially diagnosed in 1995 with cutaneous melanoma presented to the authors’ institution in 2009 with metastatic, BRAF V600E-mutant melanoma. His treatment course to date has included surgery, adjuvant radiotherapy, and interferon, metastasectomies, granulocyte-macrophage colony-stimulating factors, a clinical trial with the BRAF inhibitor vemurafenib (PLX-4032), clinical trial with combination BRAF plus MEK inhibition with vemurafenib plus GDC-0973, and combination targeted and immune therapy with vemurafenib plus the anti-CTLA4 antibody ipilimumab. This case report illustrates the long-term management of a patient with metastatic melanoma using targeted and immune therapy, evolution in treatment guidelines, next directions in research, and the critical role of clinical trials in advancement of patient care.
The PROGRESS trial three years later: Evangelism is understandable
Authors: Peter Ward
Journal: BMJ (2004)

EDITOR—I think the reasons for the evangelical tone of the last paragraph of the commentary by MacMahon et al on the PROGRESS trial are that the authors are academic specialists in medicine.1 They have a clear view from their hill over the confused swampy lowlands of everyday practice and believe they can help guide us poor souls groping about in it. …
THE IMMEDIATE EFFECTS OF UNILATERAL NEPHRECTOMY ON OPEN GLOMERULI AND URINE OUTPUT
Authors: Robert A. Moore, Ward W. Summerville
Journal: The Journal of Experimental Medicine (1931)

1. Renal shock with oliguria or anuria after unilateral kidney operation has not been produced in seventeen rabbits. 2. For a period of 2 hours after unilateral nephrectomy the one kidney carries on a proportionate part of the work of the previous two kidneys, and there is no evidence of functional compensation. 3. There is a general correlation between open glomeruli and urine output.
Multicentric glial brain tumors of a varying degree of differentiation in patient with chronic lymphocytic leukemia
Authors: Vlatko Pejsa, Ivica Grgurevic, Leo Pazanin, Nada Lang, Lovorka Grgurevic, Ozren Jaksic
Journal: American Journal of Hematology (2005)

Chronic lymphocytic leukemia is associated with an increased incidence of secondary neoplasms. Primary brain tumors are rarely seen; however, an increased risk relative to the general population has been observed in male patients with chronic lymphocytic leukemia. A case report of a 62-year-old man with progressive chronic lymphocytic leukemia and pronounced neurologic symptoms is presented. Richter's syndrome or brain infiltration with leukemia cells was clinically suspected and suggested by computed tomography findings. Progression of the neurologic symptoms rapidly continued and the patient died. Neuropathologic examination revealed multicentric glial tumors of a varying degree of differentiation located throughout the brain and cerebellum.
Abstract 12544: Dimethyloxalylglycine Treatment of Brain-Dead Donor Rats Improves Both Donor and Graft Left-Ventricular Function After Heart Transplantation
Authors: Peter Hegedüs, Shiliang Li, Sevil Korkmaz, Tamás Radovits, Samer Alsaid, Matthias Karck, Béla Merkely, Gábor Szabó
Journal: Circulation (2014)

Introduction: Cardiac transplantation is the most effective treatment of end-stage heart failure. Brain dead (BD) donors are currently the only reliable source for cardiac grafts. However, hemodynamic instability and cardiac dysfunction have been demonstrated in BD donors and this could therefore also affect posttransplant graft function. Hypothesis: Based upon the protective effect of Prolyl-Hydroxylase (PHD)-Hypoxia Inducible Factor (HIF)-1 pathway against ischemia/reperfusion injury (IRI), we tested the hypothesis that treatment of BD donor rats with the PHD inhibitor dimethyloxalylglycine (DMOG) results in a better graft heart condition in recipients after heterotopic transplantation. Methods: Lewis rats were injected with one shot DMOG (30 mg/kg i.v.) (n=7) or equal volume of physiological saline (n=7) and maintained BD for 5h by a subdurally placed and inflated balloon catheter. Controls were sham-operated (n=11). Then, hearts were explanted, stored in cold preservation solution, heterotopically transplanted and after 1.5h reperfusion left-ventricular (LV) graft function was evaluated in vivo . Myocardial histological and molecular biological analyses were performed. Results: BD was associated with decreased LV function. DMOG treatment of BD animals resulted in better load-independent contractility and end-diastolic stiffness parameters (ESPVR E' max (mmHg/μl): BD+DMOG: 3.7±0.6 vs BD: 3.1±0.5; EDPVR (mmHg/μl): BD+DMOG: 0.13±0.03 vs BD: 0.31±0.06 p&lt;0.05). Following transplantation, DMOG treatment of BD donors significantly improved altered LV systolic and diastolic function (at 80μL volume dP/dt max (mmHg/s): BD+DMOG: 2284±213 vs BD: 1854±124 p&lt;0.05; dP/dt min (mmHg/s): BD+DMOG: 1586±183 vs BD: 1154±74, p&lt;0.05; Tau-W (ms): BD+DMOG: 33±4 vs BD: 43±9 p&lt;0.05). Significantly lower myocardial inflammatory cell infiltration, necrosis, and DNA-strand breakage were evident in DMOG treated BD group compared to BD group. Conclusions: Pre-treatment of BD heart donors with DMOG resulted in a significantly better LV graft function after transplantation. These results support the view that preconditioning of BD donors through the activation of HIF-1 pathway has a protective role against myocardial IRI after transplantation.
Diagnostic accuracy of clinical tests for diagnosis of ankle syndesmosis injury: a systematic review
Authors: Amy D Sman, Claire E Hiller, Kathryn M Refshauge
Journal: British Journal of Sports Medicine (2012)

<h3>Objectives</h3> To determine the value of clinical tests for accurate diagnosis of ankle syndesmosis injury. <h3>Design</h3> Systematic review. <h3>Data sources</h3> An electronic database search was conducted (to 6 August 2012) of databases such as: MEDLINE, CINAHL, EMBASE, PubMed and Cochrane Databases. References from identified articles were examined and seven authors of eligible studies were contacted for additional information. <h3>Study selection</h3> Studies of any design, without language restriction, were included; however, systematic reviews were excluded. Eligible studies included participants with a suspected ankle syndesmosis injury but without fracture. Reliability studies compared one or more clinical tests and studies of test accuracy compared the clinical test with a reference standard. <h3>Results</h3> The database search resulted in 114 full text articles which were assessed for eligibility. Three studies were included in the review and raw data of these studies were retrieved after contacting the authors. Eight clinical diagnostic tests were investigated; palpation of the tibiofibular ligaments, external rotation stress test, squeeze, Cotton, fibula translation, dorsiflexion range of motion (ROM) and anterior drawer tests. Two studies investigated diagnostic accuracy and both investigated the squeeze test by with conflicting results. Likelihood ratios (LR) ranging from LR+1.50 to LR−1.50 were found for other tests. High intra-rater reliability was found for the squeeze, Cotton, dorsiflexion ROM and external rotation tests (83–100% close agreement). Inter-rater reliability was good for the external rotation test (ICC<sub>2,1</sub>&gt;0.70). Fair-to-poor reliability was found for other tests. <h3>Conclusions</h3> This is the first systematic review to investigate the reliability and accuracy of clinical tests for the diagnosis of ankle syndesmosis injury. Few studies were identified and our findings show that clinicians cannot rely on a single test to identify ankle syndesmosis injury with certainty. Additional diagnostic tests, such as MRI, should be considered before making a final diagnosis of syndesmosis injury.
RECENT TRENDS IN APHASIC RESEARCH
Authors: ESTI D. FREUD
Journal: American Journal of Psychiatry (1953)

This article is confined to a limited survey of contemporary literature and research on aphasia. An attempt has been made to correlate 3 different approaches to the subject in order to bring some unification to the problems involved. These 3 approaches investigate the pathological phenomena of speech and language, labelled aphasia, from the anatomic-physiological, the psycho-mechanistic, and the structural- linguistic points of view. Wiener's theory, which compares the human brain and nervous system to a highly complicated calculating machine or to a telephone switchboard service, was confirmed by Penfield and Rasmussen's anatomical findings on the operating table. Their findings refute the theory of previous authors that association areas utilize transcortical pathways. Penfield suggests that the mechanism responsible for the coordination of the speech centers is more probably mediated by subcortical projection pathways. Penfield distinguishes between inborn and acquired connection patterns. With the exception of the temporal cortex, Penfield and his co-workers could not discover any positive evidence for acquired neuron connection patterns. In the temporal cortex only, electrical stimulation and epileptic discharge were able to bring to consciousness visual memories, auditory memories, and combined memories. They deduce, therefore, that "memory" is filed in the temporal cortex. The linguistic-structural point of view is represented by the Dutch scientist Grewel. His observations in regard to aphasic patients whose linguistic faculties have suffered seem to indicate the presence of lesions in the temporal lobe of the dominant hemisphere. According to Penfield and Rasmussen it is there, as a result of a high level of neuronal integration, that memory patterns activating speech are formed. The different phenomena of aphasic disturbances can best be explained by lesions in the dominant hemisphere that involve the destruction or disruption of acquired patterns of neuronal pathways. The symptoms may evidence injuries to acquired afferent and efferent synaptic chains of neuronal mechanisms.
The pathogenesis of bone erosions in gouty arthritis
Authors: Naomi Schlesinger, Ralf G Thiele
Journal: Annals of the Rheumatic Diseases (2010)

The characteristic radiographic hallmarks of chronic gouty arthritis are the presence of macroscopic tophi and erosions with overhanging edges and relative preservation of the joint space. In recent years there has been more insight into the processes underlying the development of bone erosions in gouty arthritis. This review discusses the mechanical, pathological, cellular and immunological factors that may have a role in the pathogenesis of bone erosions in gouty arthritis. It highlights the evidence suggesting that monosodium urate crystal deposition is associated with the presence of underlying osteoarthritis and the important role of osteoclasts and the receptor for activation of nuclear factor κ B (RANK) and RANK ligand (RANK-RANKL) pathway in the pathogenesis of gouty erosions. Gouty arthritis is primarily driven by interleukin 1β (IL-1β). IL-1β has been implicated in bone destruction and erosions in other inflammatory arthridities. Thus, future IL-1 inhibitors may prevent and treat erosion formation due to tophaceous gouty arthritis. This review discusses imaging modalities and highlights ultrasongraphic evidence suggesting a significant relationship between the presence of the gouty tophus and bone erosions as well as the frequent presence of persistent low-grade inflammation in asymptomatic chronic tophaceous gouty arthritis on high-resolution ultrasonography. It is the tophus eroding the underlying bone that is pivotal for the development of bone erosions in gouty arthritis.
Effectiveness of incentive spirometry in patients following thoracotomy and lung resection including those at high risk for developing pulmonary complications
Authors: Paula Agostini, Babu Naidu, Hayley Cieslik, Richard Steyn, Pala Babu Rajesh, Ehab Bishay, Maninder Singh Kalkat, Sally Singh
Journal: Thorax (2013)

<h3>Background</h3> Following thoracotomy, patients frequently receive routine respiratory physiotherapy which may include incentive spirometry, a breathing technique characterised by deep breathing performed through a device offering visual feedback. This type of physiotherapy is recommended and considered important in the care of thoracic surgery patients, but high quality evidence for specific interventions such as incentive spirometry remains lacking. <h3>Methods</h3> 180 patients undergoing thoracotomy and lung resection participated in a prospective single-blind randomised controlled trial. All patients received postoperative breathing exercises, airway clearance and early mobilisation; the control group performed thoracic expansion exercises and the intervention group performed incentive spirometry. <h3>Results</h3> No difference was observed between the intervention and control groups in the mean drop in forced expiratory volume in 1 s on postoperative day 4 (40% vs 41%, 95% CI −5.3% to 4.2%, p=0.817), the frequency of postoperative pulmonary complications (PPC) (12.5% vs 15%, 95% CI −7.9% to 12.9%, p=0.803) or in any other secondary outcome measure. A high-risk subgroup (defined by ≥2 independent risk factors; age ≥75 years, American Society of Anaesthesiologists score ≥3, chronic obstructive pulmonary disease (COPD), smoking status, body mass index ≥30) also demonstrated no difference in outcomes, although a larger difference in the frequency of PPC was observed (14% vs 23%) with 95% CIs indicating possible benefit of intervention (−7.4% to 2.6%). <h3>Conclusions</h3> Incentive spirometry did not improve overall recovery of lung function, frequency of PPC or length of stay. For patients at higher risk for the development of PPC, in particular those with COPD or current/recent ex-smokers, there were larger observed actual differences in the frequency of PPC in favour of the intervention, indicating that investigations regarding the physiotherapy management of these patients need to be developed further.
Including Persons With HIV Infection in Cancer Clinical Trials
Authors: Govind C. Persad, Richard F. Little, Christine Grady
Journal: Journal of Clinical Oncology (2008)

Clinical research endeavors to advance medical therapy. Application of research findings may not be valid for populations whose demographics diverge substantially from that of the research sample. Comparability of the study population and the general population of interest depends on adequate sampling. Restricted research access may vitiate valid inferences for those not represented. If the ensuing medical research data are valid for some, but not others, then questions of fairness and justice are raised. These considerations led the National Institutes of Health and the Food and Drug Administration to require historically excluded so-called vulnerable study participants (such as women, children, and minorities) to be included in clinical research unless there are compelling scientific and ethical grounds for exclusion. Persons have also been excluded from research on the basis of specific physiologic conditions, such as HIV infection, for multiple reasons, including vulnerability. However, the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) advises researchers that “Individuals known to be HIV-positive should not be arbitrarily excluded from participation in clinical cancer treatment trials,” and requires scientific justification for exclusion. Improvements in HIV medicine have led to a need for further consideration of this issue. Since the 1996 introduction of highly active antiretroviral therapy (HAART), deaths caused by HIV and AIDS have decreased substantially; a recent Danish study found a nearly five-fold decrease in HIV-associated mortality between 1996 and 2005. HIV treatment goals are now chronic management and health preservation. Opportunistic infections that typified the pre-HAART era are now rare. However, a higher incidence of certain non–AIDS-defining cancers (NADC) has recently been noted. For example, lung cancer and Hodgkin’s lymphoma occur substantially more frequently in persons with HIV infection than in the background population. In light of these trends, we argue that persons with HIV infection should be appropriately evaluated for inclusion in cancer clinical trials.
Course and outcome in bipolar affective disorder: a longitudinal follow- up study
Authors: J F Goldberg, M Harrow, L S Grossman
Journal: American Journal of Psychiatry (1995)

A number of recent studies have questioned whether, despite modern treatment, the natural course of bipolar illness today still involves multiple relapses and impaired psychosocial functioning. This prospective follow-up study examined longitudinal outcome in a large group of inpatients with affective disorders.Fifty-one bipolar manic patients and 49 unipolar depressed patients were interviewed three times: 1) during hospitalization, 2) approximately 2 years after discharge, and 3) approximately 4.5 years after discharge. Subjects were treated under routine conditions and assessed for global adjustment, rehospitalization, and work and social functioning.Only 41% of the bipolar group had a good overall outcome by the time of the 4.5-year follow-up. The bipolar patients had more severe work impairment than the unipolar group. More than one-half of the bipolar patients were rehospitalized at least once during the 4.5-year follow-up period. Outcome for both diagnostic groups improved significantly over time.Many contemporary bipolar patients demonstrate gradual improvement in the first several years after hospitalization. However, a subgroup approaching 60% still experience poor posthospital adjustment in one or more areas of functioning.
Expression and prognostic significance of LIVIN, SURVIVINand other apoptosis-related genes in the progression of superficial bladder cancer
Authors: P. Gazzaniga, A. Gradilone, L. Giuliani, O. Gandini, I. Silvestri, I. Nofroni, G. Saccani, L. Frati, A.M. Aglianò
Journal: Annals of Oncology (2002)
Fluid-Structure Interaction Analyses of Stented Abdominal Aortic Aneurysms
Authors: C. Kleinstreuer, Z. Li, M.A. Farber
Journal: Annual Review of Biomedical Engineering (2007)

Rupture of abdominal aortic aneurysms (AAAs) alone is the thirteenth leading cause of death in the United States. Thus, reliable AAA-rupture risk prediction is an important advancement. If repair becomes necessary, the minimally invasive technique of inserting a stent-graft (SG), commonly referred to as endovascular aneurysm repair (EVAR), is a viable option in many cases. However, postoperative complications, such as endoleaks and/or SG migration, may occur. Computational fluid-structure interaction simulations provide physical insight into the hemodynamics coupled with multi-wall mechanics' function as an assessment tool for optimal SG placement and improved device design.
Vaccine strain varicella-zoster virus–induced central nervous system vasculopathy as the presenting feature of DOCK8 deficiency
Authors: Angela Sabry, Pia J Hauk, Huie Jing, Helen C Su, Nicholas V Stence, David M Mirsky, Maria A Nagel, Jordan K Abbott, Leonard L Dragone, Jennifer Armstrong-Wells, Donna J Curtis, Randall Cohrs, D Scott Schmid, Don Gilden, Erwin W Gelfand
Journal: Journal of Allergy and Clinical Immunology (2014)