tbuckley/cabot-search huggingface dataset:
Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin-induced thrombocytopenia-reactive antibodies or with true HIT (HIT-reactive antibodies plus thrombocytopenia): An 11-year experience
Authors: George Palatianos, Alkiviadis Michalis, Petros Alivizatos, Stavroula Lacoumenda, Stefanos Geroulanos, Andreas Karabinis, Eugenia Iliopoulou, Giannoula Soufla, Chryso Kanthou, Mazen Khoury, Petros Sfyrakis, George Stavridis, George Astras, Maria Vassili, Christina Antzaka, Katerina Marathias, Ioannis Kriaras, Androniki Tasouli, Kyrillos Papadopoulos, Marina Katafygioti, Nikoletta Matoula, Antonios Angelidis, Euthemia Melissari
Journal: American Journal of Hematology (2015)

Thrombocytopenia and thromboembolism(s) may develop in heparin immune-mediated thrombocytopenia (HIT) patients after reexposure to heparin. At the Onassis Cardiac Surgery Center, 530 out of 17,000 patients requiring heart surgery over an 11-year period underwent preoperative HIT assessment by ELISA and a three-point heparin-induced platelet aggregation assay (HIPAG). The screening identified 110 patients with HIT-reactive antibodies, out of which 46 were also thrombocytopenic (true HIT). Cardiac surgery was performed in HIT-positive patients under heparin anticoagulation and iloprost infusion. A control group of 118 HIT-negative patients received heparin but no iloprost during surgery. For the first 20 patients, the dose of iloprost diminishing the HIPAG test to ≤5% was determined prior to surgery by in vitro titration using the patients' own plasma and donor platelets. In parallel, the iloprost "target dose" was also established for each patient intraoperatively, but before heparin administration. Iloprost was infused initially at 3 ng/kg/mL and further adjusted intraoperatively, until ex vivo aggregation reached ≤5%. As a close correlation was observed between the "target dose" identified before surgery and that established intraoperatively, the remaining 90 patients were administered iloprost starting at the presurgery identified "target dose." This process significantly reduced the number of intraoperative HIPAG reassessments needed to determine the iloprost target dose, and reduced surgical time, while maintaining similar primary clinical outcomes to controls. Therefore, infusion of iloprost throughout surgery, under continuous titration, allows cardiac surgery to be undertaken safely using heparin, while avoiding life-threatening iloprost-induced hypotension in patients diagnosed with HIT-reactive antibodies or true HIT.
Guidelines for the Management of Pediatric and Adult Tumor Lysis Syndrome: An Evidence-Based Review
Authors: Bertrand Coiffier, Arnold Altman, Ching-Hon Pui, Anas Younes, Mitchell S. Cairo
Journal: Journal of Clinical Oncology (2008)

Tumor lysis syndrome (TLS) has recently been subclassified into either laboratory TLS or clinical TLS, and a grading system has been established. Standardized guidelines, however, are needed to aid in the stratification of patients according to risk and to establish prophylaxis and treatment recommendations for patients at risk or with established TLS.A panel of experts in pediatric and adult hematologic malignancies and TLS was assembled to develop recommendations and guidelines for TLS based on clinical evidence and standards of care. A review of relevant literature was also used.New guidelines are presented regarding the prevention and management of patients at risk of developing TLS. The best management of TLS is prevention. Prevention strategies include hydration and prophylactic rasburicase in high-risk patients, hydration plus allopurinol or rasburicase for intermediate-risk patients, and close monitoring for low-risk patients. Primary management of established TLS involves similar recommendations, with the addition of aggressive hydration and diuresis, plus allopurinol or rasburicase for hyperuricemia. Alkalinization is not recommended. Although guidelines for rasburicase use in adults are provided, this agent is currently only approved for use in pediatric patients in the United States.The potential severity of complications resulting from TLS requires measures for prevention in high-risk patients and prompts treatment in the event that symptoms arise. Recognition of risk factors, monitoring of at-risk patients, and appropriate interventions are the key to preventing or managing TLS. These guidelines should assist in the prevention of TLS and improve the management of patients with established TLS.
Stereoselective block of cardiac sodium channels by RAC109 in single guinea pig ventricular myocytes.
Authors: C W Clarkson
Journal: Circulation Research (1989)

The effects of the optical stereoisomers of the local anesthetic RAC109 (RAC109-I and RAC109-II) on sodium current in isolated guinea pig ventricular myocytes were investigated by use of the whole-cell variation of the patch-clamp technique. RAC109-I and RAC109-II produced similar levels of tonic block, but RAC109-I produced a significantly larger use-dependent block on repetitive pulsing to potentials positive to -60 mV. Definition of the time courses of block development at -20 mV and recovery at -140 and -160 mV indicated that RAC109-I had a higher affinity for activated and inactivated channels and dissociated more slowly at hyperpolarized potentials compared with RAC109-II. Removal of fast inactivation by alpha-chymotrypsin intensified tonic block but did not reduce use-dependent block by RAC109-I; this finding suggests that channel inactivation is not necessary for use-dependent block. The guarded-receptor model was used to calculate apparent rate constants of drug binding and unbinding. According to the model, RAC109-I and RAC109-II have significantly different unbinding rate constants for channels when they exist predominantly in rested, activated, or inactivated states, as well as significantly different binding rate constants when channels are activated. However, the apparent rates of drug binding to closed (rested and inactivated) channels are not significantly different for the two isomers; this finding indicates that drug binding to closed channels is not markedly stereospecific, in contrast to unbinding. The effects of RAC109 stereoisomers on cardiac sodium channels were also qualitatively similar to those previously reported in nerve; these findings suggest that the binding sites for local anesthetics in both tissue types have a similar structural topography.
Effort processes in achieving performance outcomes: Interrelations among and roles of core constructs
Authors: Rex A. Wright, Giuseppe Pantaleo
Journal: Behavioral and Brain Sciences (2013)

Abstract We address points of confusion pertaining to interrelations among and roles of core constructs involved in the production of performance outcomes. We do so informed by the body of work derived from Brehm's seminal motivation intensity theory – in particular an elaboration from the theory concerned with fatigue influence on effort and associated cardiovascular responses in people confronted with performance challenges.
Cell Adhesion Molecules, Vascular Endothelial Growth Factor, and Basic Fibroblast Growth Factor in Patients with Non–Small Cell Lung Cancer Treated with Chemotherapy with or without Bevacizumab—an Eastern Cooperative Oncology Group Study
Authors: Afshin Dowlati, Robert Gray, Alan B. Sandler, Joan H. Schiller, David H. Johnson
Journal: Clinical Cancer Research (2008)

Abstract Background: E4599 was a phase II/phase III trial, in which 878 patients with advanced non–small cell lung cancer were randomized to carboplatin + paclitaxel (PC arm) or PC + bevacizumab (BPC arm). Survival and progression-free survival were superior on the BPC arm. The rationale for markers used in this correlative study was based on elevated vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), soluble intercellular adhesion molecule (ICAM) and E-selectin in a variety of malignances and changes in response to endothelial cell apoptosis. Materials and Methods: Prospective correlates included measurements of pretreatment plasma VEGF, as well as pretreatment and week 7, bFGF, ICAM, and E-selectin. Low and high levels were defined as less than or equal to or more than the median. Results: E-selectin (P &amp;lt; 0.0001) showed a decrease and bFGF showed an increase (P = 0.004) from baseline at week 7, which were similar in both arms. Baseline ICAM showed significant associations with response and survival in both groups. Patients with low baseline ICAM had a higher response rate (32% versus 14%; P = 0.02), better overall survival (P = 0.00005), and better 1-year survival (65% versus 25%) than those with high ICAM, respectively, regardless of treatment arm. Patients with high VEGF levels were more likely to respond to BPC compared with PC, but this was not predictive of survival. The results also suggest a benefit from bevacizumab for patients with low baseline ICAM levels (53% reduction in the progression-free survival hazard rate). Conclusions: In this study, baseline ICAM levels were prognostic for survival and predictive of response to chemotherapy with or without bevacizumab. VEGF levels were predictive of response to bevacizumab but not survival.
Mechanisms Mediating the Renal Profibrotic Actions of Vasoactive Peptides in Transgenic Mice
Authors: JEAN-CLAUDE DUSSAULE, PIERRE-LOUIS THARAUX, JEAN-JACQUES BOFFA, FADI FAKHOURI, RAYMOND ARDAILLOU, CHRISTOS CHATZIANTONIOU
Journal: Journal of the American Society of Nephrology (2000)

Transgenic mice are useful tools to investigate the mechanisms of the renal profibrotic actions of endothelin and angiotensin II. The overexpression of angiotensinogen and renin genes induces renal sclerosis independently of changes in systemic hemodynamics. The same results are observed when the endothelin-1 gene is overexpressed. Transgenic mice harboring the luciferase gene, under the control of the collagen I alpha2 chain promoter, and made hypertensive by induction of a nitric oxide (NO) deficiency have been studied. In this strain of mice, luciferase activity is an early index of renal and vascular fibrosis. Luciferase activity was increased in preglomerular arterioles and glomeruli when mice were treated with N:(omega)-nitro-L-arginine methyl ester, an inhibitor of NO synthases. Bosentan (an endothelin receptor antagonist) was as efficient as losartan (an AT1 receptor antagonist) in preventing renal fibrosis, although it did not decrease BP. In short-term experiments, angiotensin II produced an increase in luciferase activity that was entirely prevented by losartan but also by bosentan. It can be concluded that, during chronic inhibition of NO, the collagen I gene is activated, which contributes to the development of nephroangiosclerosis and glomerulosclerosis. Angiotensin II plays a major role in this fibrogenic process, and its effect is at least partly independent of systemic hemodynamics and mediated by the profibrotic action of endothelin-1.
The demise of nursing in the United Kingdom: a warning for medicine
Authors: L. Shields, R. Watson
Journal: Journal of the Royal Society of Medicine (2007)

The 19th century teaches us that nurses must be central to the running of all aspects of hospitals, not just those areas deemed appropriate by the medical profession. This will require not only improved nursing leadership but also enhanced opportunities for nurses to realise their potential through education and training.1 (p. 1396)
Managed Care and Physicians' Provision of Charity Care
Authors: Peter J. Cunningham
Journal: JAMA (1999)

ContextHealth system changes may be affecting the ability of physicians to provide care with little or no compensation from patients who are uninsured and underinsured and may result in decreased access to physicians for uninsured persons.ObjectiveTo examine the association between managed care and physicians' provision of charity care.DesignThe 1996-1997 Community Tracking Study physician survey.Setting and ParticipantsA nationally representative sample of 10,881 physicians from 60 randomly selected communities.Main Outcome MeasureThe number of hours in the month prior to the interview that the physician provided care for free or at reduced fees because of the financial need of the patient.ResultsOverall, 77.3% of respondents provided an average of 10.3 hours of charity care per week. Physicians who derive at least 85% of their practice revenue from managed care plans were considerably less likely to provide charity care and spend fewer hours providing charity care than physicians with little involvement in managed care plans (P=.01). In addition, physicians who practice in areas with high managed care penetration provided fewer hours of charity care than physicians in other areas, regardless of their own level of involvement with managed care (P<.01). Differences in charity care provision were also shown for other important factors, including ownership of the practice and practice arrangements (more charity care occurred in solo and 2-physician practices; P<.01).ConclusionPhysicians involved with managed care plans and those who practice in areas with high managed care penetration tend to provide less charity care.
Breast milk fatty acids and allergic disease in preschool children: The Prevention and Incidence of Asthma and Mite Allergy birth cohort study
Authors: Alet H. Wijga, Adriana C. van Houwelingen, Marjan Kerkhof, Cora Tabak, Johan C. de Jongste, Jorrit Gerritsen, Hendriek Boshuizen, Bert Brunekreef, Henriette A. Smit
Journal: Journal of Allergy and Clinical Immunology (2006)
Ethical, Scientific, and Regulatory Perspectives Regarding the Use of Placebos in Cancer Clinical Trials
Authors: Christopher K. Daugherty, Mark J. Ratain, Ezekiel J. Emanuel, Ann T. Farrell, Richard L. Schilsky
Journal: Journal of Clinical Oncology (2008)

To examine the ethical, scientific, and regulatory issues in the design and conduct of placebo-controlled cancer clinical trials.Several content experts contributed to this article.Specific criteria can be applied to determine the appropriate use of placebos in oncology drug development. Placebo controls may be justified to prove efficacy of a new treatment in diseases with high placebo response rates; in conditions that wax and wane in severity, have spontaneous remissions, or have an uncertain and unpredictable course; when existing therapies are minimally effective or have serious adverse effects; or in the absence of effective therapy. Use of placebos may also be justified to assure blinding of physicians and patients regarding treatment assignment so as to minimize bias in assessment of study end points. If a trial meets these methodologic criteria, it must then fulfill additional criteria to be considered ethical. These criteria include full disclosure to patients and an assurance that participants randomly assigned to placebo are not substantially more likely than those in active treatment group(s) to die; suffer irreversible morbidity, disability, or other substantial harms; suffer reversible but serious harm; or suffer severe discomfort.We conclude that placebo-controlled oncology trials are scientifically feasible, ethically justifiable, and may be necessary or desirable to meet regulatory standards for drug approval. Using cross-over or randomized withdrawal trial designs, requiring inclusion of state-of-the-art palliative care, and developing valid and acceptable surrogates for survival are critical strategies to address some of the ethical dilemmas associated with placebo-controlled trials.
Neurovascular Factors in Wound Healing in the Foot Skin of Type 2 Diabetic Subjects
Authors: Singhan T.M. Krishnan, Cristian Quattrini, Maria Jeziorska, Rayaz A. Malik, Gerry Rayman
Journal: Diabetes Care (2007)

Delayed wound healing in diabetic patients without large-vessel disease has been attributed to microvascular dysfunction, neuropathy, and abnormal cellular and inflammatory responses. The role of these abnormalities has mainly been examined in animal models. Few studies have been undertaken in diabetic patients, and those that have are limited due to analysis in wounds from chronic ulcers. In this study, we quantified the rate of wound healing in relation to skin neurovascular function and structure following a dorsal foot skin biopsy in type 2 diabetes.Twelve healthy control subjects and 12 type 2 diabetic subjects with neuropathy but without macrovascular disease were studied. We quantified rate of wound healing and related it to skin microvascular function (laser Doppler imager [LDI](max)), blood vessel density, small nerve fiber function (LDI(flare)) and nerve fiber density, vascular endothelial growth factor (VEGF) and its receptor (FLK1), and hypoxia-inducible factor (HIF)-1alpha expression.The rate of wound closure was identical between control subjects and diabetic patients despite a significant reduction in maximum hyperemia (LDI(max)), epidermal and dermal VEGF-A, and epidermal and dermal blood vessel VEGFR-2 expression as well as the neurogenic flare response (LDI(flare)) and dermal nerve fiber density. There was no significant difference in HIF-1alpha and dermal blood vessel density between control subjects and diabetic patients.In conclusion, the results of this study suggest that wound closure in subjects with type 2 diabetes is not delayed despite significant alterations in neurovascular function and structure.
Critical role for programmed death 1 signaling and protein kinase B in augmented regulatory T-cell induction in cord blood
Authors: Sytze de Roock, Sanne B.E.A. Hoeks, Linda Meurs, Anouk Steur, Maarten O. Hoekstra, Berent J. Prakken, Marianne Boes, Ismé M. de Kleer
Journal: Journal of Allergy and Clinical Immunology (2011)
Targeting Cell Membrane Lipid Rafts by Stoichiometric Functionalization of Gold Nanoparticles with a Sphingolipid-Binding Domain Peptide
Authors: David Paramelle, Daniel Nieves, Benjamin Brun, Rachel S. Kraut, David G. Fernig
Journal: Advanced Healthcare Materials (2015)

A non‐membrane protein‐based nanoparticle agent for the tracking of lipid rafts on live cells is produced by stoichiometric functionalization of gold nanoparticles with a previously characterized sphingolipid‐ and cell membrane microdomain‐binding domain peptide (SBD). The SBD peptide is inserted in a self‐assembled monolayer of peptidol and alkane thiol ethylene glycol, on gold nanoparticles surface. The stoichiometric functionalization of nanoparticles with the SBD peptide, essential for single molecule tracking, is achieved by means of non‐affinity nanoparticle purification. The SBD‐nanoparticles have remarkable long‐term resistance to electrolyte‐induced aggregation and ligand‐exchange and have no detectable non‐specific binding to live cells. Binding and diffusion of SBD‐nanoparticles bound to the membrane of live cells is measured by real‐time photothermal microscopy and shows the dynamics of sphingolipid‐enriched microdomains on cells membrane, with evidence for clustering, splitting, and diffusion over time of the SBD‐nanoparticle labeled membrane domains. The monofunctionalized SBD‐nanoparticle is a promising targeting agent for the tracking of lipid rafts independently of their protein composition and the labelling requires no prior modification of the cells. This approach has potential for further functionalization of the particles to manipulate the organization of, or targeting to microdomains that control signaling events and thereby lead to novel diagnostics and therapeutics.
GP role in maternity care should be renewed and strengthened, says think tank
Authors: A. O'Dowd
Journal: BMJ (2010)

The use of replication-deficient adenoviruses as vehicles for transfer of foreign genes offers many advantages in a vaccine setting, eliciting strong cellular immune responses involving both CD8<sup>+</sup> and CD4<sup>+</sup> T cells. Further improving the immunogenicity, tethering of the inserted target Ag to MHC class II–associated invariant chain (Ii) greatly enhances both the presentation of most target Ags, as well as overall protection against viral infection, such as lymphocytic choriomeningitis virus (LCMV). The present study extends this vaccination concept to include protection against intracellular bacteria, using <i>Listeria monocytogenes</i> as a model organism. Protection in C57BL/6 mice against recombinant <i>L. monocytogenes</i> expressing an immunodominant epitope of the LCMV glycoprotein (GP33) was greatly accelerated, augmented, and prolonged following vaccination with an adenoviral vaccine encoding GP linked to Ii compared with vaccination with the unlinked vaccine. Studies using knockout mice demonstrated that CD8<sup>+</sup> T cells were largely responsible for this protection, which is mediated through perforin-dependent lysis of infected cells and IFN-γ production. Taking the concept a step further, vaccination of C57BL/6 (<i>L. monocytogenes</i>–resistant) and BALB/c (<i>L. monocytogenes</i>–susceptible) mice with adenoviral vectors encoding natural <i>L. monocytogenes</i>-derived soluble Ags (listeriolysin O and p60) revealed that tethering of these Ags to Ii markedly improved the vaccine-induced CD8<sup>+</sup> T cell response to two of three epitopes studied. More importantly, Ii linkage accelerated and augmented vaccine-induced protection in both mouse strains and prolonged protection, in particular that induced by the weak Ag, p60, in <i>L. monocytogenes</i>–susceptible BALB/c mice.
Bronchial carcinoid tumours
Authors: R. A. Smith
Journal: Thorax (1969)

Some features of 22 cases of carcinoid tumour are described. The histology of the tumour was the criterion for inclusion in the series. The histology was reviewed by an observer unfamiliar with the clinical features. Six patients, each with an entirely endobronchial tumour of typical histology treated satisfactorily by surgery, are excluded from further consideration; the remaining 16 are considered for factors which may be significant in assessing the long-term prognosis, in addition to a histological assessment. The experience in this series is compared with a number of considerably larger series from the literature. The conclusion is reached that no single feature, histological or clinical, can be a basis for reaching a reliable prognosis. Lobectomy is regarded as the operation of choice in treatment.
Targeted Magnetic Nanoparticles for Remote Magnetothermal Disruption of Amyloid‐β Aggregates
Authors: Colleen N. Loynachan, Gabriela Romero, Michael G. Christiansen, Ritchie Chen, Rachel Ellison, Tiernan T. O'Malley, Ulrich P. Froriep, Dominic M. Walsh, Polina Anikeeva
Journal: Advanced Healthcare Materials (2015)

Remotely triggered hysteretic heat dissipation by magnetic nanoparticles (MNPs) selectively attached to targeted proteins can be used to break up self-assembled aggregates. This magnetothermal approach is applied to the amyloid-β (Aβ) protein, which forms dense, insoluble plaques characteristic of Alzheimer's disease. Specific targeting of dilute MNPs to Aβ aggregates is confirmed via transmission electron microscopy (TEM) and is found to be consistent with a statistical model of MNP distribution on the Aβ substrates. MNP composition and size are selected to achieve efficient hysteretic power dissipation at physiologically safe alternating magnetic field (AMF) conditions. Dynamic light scattering, fluorescence spectroscopy, and TEM are used to characterize the morphology and size distribution of aggregates before and after exposure to AMF. A dramatic reduction in aggregate size from microns to tens of nanometers is observed, suggesting that exposure to an AMF effectively destabilizes Aβ deposits decorated with targeted MNPs. Experiments in primary hippocampal neuronal cultures indicate that the magnetothermal disruption of aggregates reduces Aβ cytotoxicity, which may enable future applications of this approach for studies of protein disaggregation in physiological environments.