tbuckley/cabot-search huggingface dataset:
Outpatient Therapy for Fever and Neutropenia Is Safe but Implementation Is the Key
Authors: Monica A. Slavin, Karin A. Thursky
Journal: Journal of Clinical Oncology (2013)

TheEuropeanmulticenterstudybyKernetal 1 thataccompaniesthis editorial shows that outpatient oral fluoroquinolone (FQ) therapy is safe in low-risk patients with fever and neutropenia after cancer chemotherapy.Although the feasibility of oral antibiotic therapy has been demonstrated, 2-5 the safety of initiating treatment with oral therapy followed by early discharge has not been rigorously examined.Kern et al also demonstrated equivalence between oral moxifloxacin and the combination of oral ciprofloxacin and amoxicillin/clavulanic acid.7][8] This study has important implications for treatment of fever and neutropenia in patients with cancer but translating these trial findings into clinical practice will require changes to treatment algorithms, the way patients with fever and neutropenia are assessed, and the way antibiotic therapy is delivered in hospitals.Key to successful implementation of an outpatient oral antibiotic programwillbemakingthecorrectchoiceofpatientandantibiotic.Additionally the infrastructure must be in place for follow-up and readmission of outpatients if required as well as for ongoing surveillance of antimicrobial susceptibility in isolates from this patient group.Thorough and accurate risk assessment on presentation with fever and neutropenia is critical.In its derivation and validation studies, the Multinational Association for Supportive Care in Cancer (MASCC) risk score predicted a group of patients with fever and neutropenia that had a less than 10% risk of serious medical complications including death. 9The score is calculated by accruing points for good outcome predictors in seven criteria such as outpatient status, age below 60 years, no dehydration, no hypotension, mild or moderate burden of illness, no chronic obstructive pulmonary disease and solid tumor or hematological malignancy, and no prior fungal infection.The maximum score is 26.The MASCC score at a cutoff of more than 20, performed well in selecting low-risk patients in the population studied by Kern et al 1 which largely comprised outpatients with solid tumors or lymphoma.The readmission rate of 5% and mortality of 1% indicates that low risk patients were accurately selected.However, not all patients with the appropriate MASCC score are suitable for this strategy, and Kern et al point out that approximately 30% of patients eligible for outpatient therapy on medical grounds were unable to be discharged due to logistical reasons such as availability of transport or carers, others could not be discharged due to medical comorbidities not captured by the MASCC score, while a small group of patients (14%) refused to be discharged.Overall at 24 hours after entering the study, only 43% of patients had been discharged.
Long-Range Neural Synchrony in Behavior
Authors: Alexander Z. Harris, Joshua A. Gordon
Journal: Annual Review of Neuroscience (2015)

Long-range synchrony between distant brain regions accompanies multiple forms of behavior. This review compares and contrasts the methods by which long-range synchrony is evaluated in both humans and model animals. Three examples of behaviorally relevant long-range synchrony are discussed in detail: gamma-frequency synchrony during visual perception, hippocampal-prefrontal synchrony during working memory, and prefrontal-amygdala synchrony during anxiety. Implications for circuit mechanism, translation, and clinical relevance are discussed.
Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling
Authors: Elen Griffith, Sarah Walker, Carol-Anne Martin, Paola Vagnarelli, Tom Stiff, Bertrand Vernay, Nouriya Al Sanna, Anand Saggar, Ben Hamel, William C Earnshaw, Penny A Jeggo, Andrew P Jackson, Mark O'Driscoll
Journal: Nature Genetics (2007)
Role of Axonal Transport in Neurodegenerative Diseases
Authors: Kurt J. De Vos, Andrew J. Grierson, Steven Ackerley, Christopher C.J. Miller
Journal: Annual Review of Neuroscience (2008)

Many major human neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), display axonal pathologies including abnormal accumulations of proteins and organelles. Such pathologies highlight damage to the axon as part of the pathogenic process and, in particular, damage to transport of cargoes through axons. Indeed, we now know that disruption of axonal transport is an early and perhaps causative event in many of these diseases. Here, we review the role of axonal transport in neurodegenerative disease.
Room-Air Resuscitation Causes Less Damage to Heart and Kidney than 100% Oxygen
Authors: Máximo Vento, Juan Sastre, Miguel A. Asensi, José Viña
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Pure oxygen causes more oxidative stress than room air in resuscitation of asphyctic neonates, and consequently could be associated with increased tissue damage.Objectives: To compare damage caused to heart and kidneys on reoxygenation in severely asphyctic term neonates resuscitated with room air (RAR) or 100% oxygen (OxR). Nonasphyctic term newborn infants served as a control group.Methods and Measurements: This is a prospective randomized clinical trial masked for the gas mixture. Reduced glutathione (GSH), oxidized glutathione (GSSG), and superoxide dismutase (SOD) activity were measured to assess oxidative stress. Plasma cardiac troponin T (cTnT) and urinary N-acetyl-glucosaminidase (NAG) assessed cardiac and renal damage, respectively. Daily determinations of NAG for a 2-wk period were performed to monitor postasphyctic renal damage.Main Results: Both asphyctic groups showed oxidative stress when compared with the control group as evidenced by diminished GSH/GSSG ratios, adaptive increases in SOD activity, and higher values of NAG and cTnT (markers of tissue damage). However, the OxR group showed significantly higher values of NAG and cTnT, lower GSH/GSSG ratios, and higher SOD activity than the RAR group. Moreover, NAG values persisted in being higher than normal in the OxR group for 2 wk after birth, whereas NAG in the RAR group dropped to normal within the first week. A linear correlation between cTnT or NAG and GSSG was found.Conclusions: The use of room air on resuscitation causes less oxidative stress and damage to heart and kidney than pure oxygen.
Correlation of Flicker-Induced and Flow-Mediated Vasodilatation in Patients With Endothelial Dysfunction and Healthy Volunteers
Authors: Berthold Pemp, Günther Weigert, Katharina Karl, Ursula Petzl, Michael Wolzt, Leopold Schmetterer, Gerhard Garhofer
Journal: Diabetes Care (2009)

OBJECTIVE Flicker-induced vasodilatation is reduced in patients with vascular-related diseases, which has at least partially been attributed to endothelial dysfunction of retinal vessels. Currently, the standard method to assess endothelial function in vivo is flow-mediated vasodilatation (FMD). Thus, the present study was performed to investigate whether a correlation exists between flicker-induced vasodilatation and FMD in patients with known endothelial dysfunction and healthy subjects. RESEARCH DESIGN AND METHODS In the present study, 20 patients with type 1 diabetes, 40 patients with systemic hypertension (systolic blood pressure 140–159 mmHg; diastolic blood pressure 90–99 mmHg) and/or serum cholesterol levels ≥0.65 mmol/l, and 20 healthy control subjects were included. The flicker response was measured using the Dynamic Retinal Vessel Analyzer. FMD was determined using a high-resolution ultrasound system, measuring brachial artery diameter reactivity during reperfusion after arterial occlusion. RESULTS The flicker response of both retinal arteries and veins was significantly reduced in the two patients groups. Likewise, FMD was significantly reduced in patients compared with healthy control subjects. However, only a weak correlation between flicker-induced vasodilatation and FMD was observed. CONCLUSIONS The study confirms that flicker responses and FMD are reduced in the selected patient groups. Whether the weak correlation between FMD and flicker is due to the different stimulation type, the different vascular beds measured, or other mechanisms has yet to be investigated.
Imaging in Local Staging of Gastric Cancer: A Systematic Review
Authors: Robert Michael Kwee, Thomas Christian Kwee
Journal: Journal of Clinical Oncology (2007)

Purpose Endoscopic ultrasound (EUS) has been established as the diagnostic modality of choice in local (T) staging of gastric cancer. Multidetector row computed tomography (MDCT) and magnetic resonance imaging (MRI) are promising alternatives. The aim of this study was to systematically review the literature regarding the performance of each of these imaging modalities. Methods A systematic search for relevant studies was performed in the PubMed/MEDLINE and EMBASE databases. Two reviewers independently assessed the methodological quality of each study. Local staging performance of included studies was calculated. Results Twenty-two EUS studies, five MDCT studies, one combined EUS and MDCT study, and three MRI studies met the inclusion criteria. The studies were of moderate methodological quality. Diagnostic accuracy of overall T staging for EUS, MDCT, and MRI varied between 65% to 92.1%, 77.1% to 88.9%, and 71.4% to 82.6%, respectively. Sensitivity for assessing serosal involvement for EUS, MDCT, and MRI varied between 77.8% to 100%, 82.8% to 100%, and 89.5% to 93.1%, respectively. Specificity for assessing serosal involvement for EUS, MDCT, and MRI varied between 67.9% to 100%, 80% to 96.8%, and 91.4% to 100%, respectively. Conclusion EUS, MDCT, and MRI achieve similar results in terms of diagnostic accuracy in T staging and in assessing serosal involvement. Most experience has been gained with EUS. Few MDCT studies and even fewer MRI studies are available. Thus, EUS remains the first-choice imaging modality in preoperative T staging of gastric cancer.
Massive haemoptysis as a late consequence of pulmonary irradiation.
Authors: R D Isaacs, W J Wattie, A U Wells, H H Rea, T R Bai
Journal: Thorax (1987)

Massive haemoptysis has not been reported as a late complication of therapeutic pulmonary irradiation.We report two cases of massive haemoptysis arising from abnormal bron- chial arteries in lung parenchyma previously exposed to therapeutic doses of radiation. Case reports PATIENT IA non-smoking caucasian woman presented in 1978, aged 23 years, with a stage IIB rhabdomyosarcoma of the right thigh.She was treated with local irradiation and intravenous chemotherapy with vincristine, actinomycin D, and cyclophosphamide.Three months later a pulmonary nodule
Exogenous Peptide and Protein Expression Levels Using Retroviral Vectors in Human Cells
Authors: Tanya M. Sandrock, Bob Risley, Burt T. Richards, Mark A. Poritz, Harry A. Austin, Sanghee Yoo, Marianne K.-H. Kim, Bruce Roth, Karen Repetny, Forrest Hsu, Mark Stump, David H.-F. Teng, Alexander Kamb
Journal: Molecular Therapy (2001)

Pseudotyped retroviral vectors combine the advantages of broad host range, high expression, stable chromosomal integration, and ease of preparation. These vectors greatly facilitate delivery into mammalian cells of sequences encoding individual peptide inhibitors—including those with therapeutic utility—and inhibitor libraries. However, retroviral vectors vary in behavior, particularly with respect to expression levels in different cell lines. Expression level is especially important in transdominant experiments because the concentration of an inhibitor (for example, an expressed peptide) is one of the key determinants in the degree of complex formation between the inhibitor and its target. Thus, inhibitor concentration should have an impact on the expressivity and/or penetrance of an induced phenotype. Here, we compare several retroviral vectors and human cell lines for relative expression levels using a green fluorescent protein reporter. We show for a subset of these lines that cellular protein concentrations produced by single-copy vectors range up to about 2 μM. We also examine other variables that contribute to expression level, such as the nature of the expressed protein's carboxy terminus. Finally, we test the effect of increased concentration on phenotype with a nine-amino-acid peptide derived from the human papilloma virus protein E7 which overcomes E7-mediated cell growth.
Role of B-Cell–Activating Factor in Adhesion and Growth of Human Multiple Myeloma Cells in the Bone Marrow Microenvironment
Authors: Yu-Tzu Tai, Xian-Feng Li, Iris Breitkreutz, Weihua Song, Paola Neri, Laurence Catley, Klaus Podar, Teru Hideshima, Dharminder Chauhan, Noopur Raje, Robert Schlossman, Paul Richardson, Nikhil C. Munshi, Kenneth C. Anderson
Journal: Cancer Research (2006)

Abstract Recent studies have underscored the role of B-cell-activating factor (BAFF), a member of the tumor necrosis factor superfamily, in promoting the survival of malignant B cells, including human multiple myeloma. We here characterized the functional significance of BAFF in the interaction between multiple myeloma and bone marrow stromal cells (BMSC) and further defined the molecular mechanisms regulating these processes. BAFF is detected on BMSCs derived from multiple myeloma patients as evidenced by flow cytometry. BAFF secretion is 3- to 10-fold higher in BMSCs than in multiple myeloma cells, and tumor cell adhesion to BMSCs augments BAFF secretion by 2- to 5-fold, confirmed by both ELISA and immunoblotting. Adhesion of MM1S and MCCAR multiple myeloma cell lines to KM104 BMSC line transfected with a luciferase reporter vector carrying the BAFF gene promoter (BAFF-LUC) significantly enhanced luciferase activity, suggesting that nuclear factor-κB (NF-κB) activation induced by multiple myeloma adhesion to BMSCs mediates BAFF up-regulation. Moreover, BAFF (0-100 ng/mL) increases adhesion of multiple myeloma lines to BMSCs in a dose-dependent manner; conversely, transmembrane activator and calcium modulator and cyclophylin ligand interactor-Ig or B-cell maturation antigen/Fc blocked BAFF stimulation. Using adenoviruses expressing dominant-negative and constitutively expressed AKT as well as NF-κB inhibitors, we further showed that BAFF-induced multiple myeloma cell adhesion is primarily mediated via activation of AKT and NF-κB signaling. Importantly, BAFF similarly increased adhesion of CD138-expressing patient multiple myeloma cells to BMSCs. These studies establish a role for BAFF in localization and survival of multiple myeloma cells in the bone marrow microenvironment and strongly support novel therapeutics, targeting the interaction between BAFF and its receptors in human multiple myeloma. (Cancer Res 2006; 66(13): 6675-82)
2-deoxy-2-[18F]fluoro-d-mannose positron emission tomography imaging in atherosclerosis
Authors: Nobuhiro Tahara, Jogeshwar Mukherjee, Hans J de Haas, Artiom D Petrov, Ahmed Tawakol, Nezam Haider, Atsuko Tahara, Cristian C Constantinescu, Jun Zhou, Hendrikus H Boersma, Tsutomu Imaizumi, Masataka Nakano, Aloke Finn, Zahi Fayad, Renu Virmani, Valentin Fuster, Lisardo Bosca, Jagat Narula
Journal: Nature Medicine (2014)
Polymorphic light eruption sine eruptione
Authors: J.S. DOVER, J.L.M. HAWK
Journal: British Journal of Dermatology (1988)

We describe seven patients, four female and three male, who developed intense pruritus on sun-exposed skin without visible change. The clinical features resembled those of polymorphic light eruption (PLE) without rash. Four patients also occasionally developed typical PLE upon sun exposure, but sun-induced pruritus alone occurred most frequently. No patient was taking any drug therapy. One patient developed similar pruritus following solar simulated irradiation, and one following PUVA therapy. All other laboratory investigations were negative. Treatment with low dose UVB phototherapy or PUVA therapy was effective. The condition, which we have called polymorphic light eruption sine eruptione (PLESE), appears to be a variant of PLE not previously reported.
A rare gastrointestinal presentation of a common malignancy
Authors: R B McCorry, B Nair, P Mooney, P L Shields
Journal: Gut (2010)

<h3>Objective</h3> To investigate mothers’ knowledge of reducing the risks for sudden infant death syndrome (SIDS) and attitudes towards safer sleep practices. <h3>Design and setting</h3> A cross-sectional survey was carried out in deprived areas of Bristol, UK. Recruitment took place in 2014 at local health visitor-led baby clinics. <h3>Participants</h3> Of 432 mothers approached, 400 (93%) completed the face-to-face survey. Participants with infants at ‘higher’ risk of SIDS (using an algorithm based on a previous observational study) were compared with those at ‘lower’ risk. <h3>Main outcome measures</h3> The survey asked participants to recall three SIDS risk reduction strategies (unprompted), and scored responses to 14 SIDS risk-related infant sleep scenarios (prompted). <h3>Results</h3> Overall, 48/400 (12%) mothers were classified as higher risk. Mothers in the higher risk group were less likely to breast feed (multivariate OR=3.59(95% CI 1.46 to 8.86)), less likely to be able to cite two or more unprompted correct SIDS risk reduction strategies (multivariate OR=2.05(95% CI 1.02 to 4.13)) and scored lower on prompted safer sleep scenarios overall. Notably, only 206/400 (52%) of all mothers surveyed (33% in the higher risk group) from these deprived areas in Bristol identified infant sleep position as a risk reduction strategy for SIDS, despite 25 years of campaigns. <h3>Conclusions</h3> Mothers in the higher risk group were disadvantaged when it came to some aspects of knowledge of SIDS risk reduction and attitudes to safer sleep. The initial ‘Back-to Sleep’ message that dramatically reduced these deaths a generation ago needs more effective promotion for today’s generation of mothers.
Human T-Cell Leukemia Virus I Tax Protein Sensitizes p53-Mutant Cells to DNA Damage
Authors: Valia T. Mihaylova, Allison M. Green, Moshe Khurgel, Oliver J. Semmes, Gary M. Kupfer
Journal: Cancer Research (2008)

Abstract Mutations in p53 are a common cause of resistance of cancers to standard chemotherapy and, thus, treatment failure. Reports have shown that Tax, a human T-cell leukemia virus type I encoded protein that has been associated with genomic instability and perturbation of transcription and cell cycle, sensitizes HeLa cells to UV treatment. The extent to which Tax can sensitize cells and the mechanism by which it exerts its effect are unknown. In this study, we show that Tax sensitizes p53-mutant cells to a broad range of DNA-damaging agents, including mitomycin C, a bifunctional alkylator, etoposide, a topoisomerase II drug, and UV light, but not ionizing radiation, a double-strand break agent, or vinblastine, a tubulin poison. Tax caused hypersensitivity in all p53-deleted cell lines and several, but not all, mutant-expressed p53–containing cell lines, while unexpectedly being protective in p53 wild-type (wt) cells. The effect observed in p53-deleted lines could be reversed for this by transfection of wt p53. We also show that Tax activates a p53-independent proapoptotic program through decreased expression of the retinoblastoma protein and subsequent increased E2F1 expression. The expression of several proapoptotic proteins was also induced by Tax, including Puma and Noxa, culminating in a substantial increase in Bax dimerization. Our results show that Tax can sensitize p53-mutant cells to DNA damage while protecting p53 wt cells, a side benefit that might result in reduced toxicity in normal cells. Such studies hold the promise of a novel adjunctive therapy that could make cancer chemotherapy more effective. [Cancer Res 2008;68(12):4843–52]
X-linked Inheritance in Females with Chronic Granulomatous Disease
Authors: Elaine L. Mills, Kenneth S. Rholl, Paul G. Quie
Journal: Journal of Clinical Investigation (1980)

Chronic granulomatous disease in males is familial and its transmission is is usually clearly x-linked. The mode of inheritance in females with the syndrome is unknown and the carrier state difficult to identify. Defective polymorphonuclear leukocyte bactericidal activity in this disease is associated with an absence of the respiratory burst generated in stimulated phagocytes and may be detected by the chemiluminescence assay. Polymorphonuclear leukocytes from three of four females with chronic granulomatous disease had extremely low chemiluminescence production, their asymptomatic mothers had intermediate values, and their fathers were normal. Polymorphonuclear neutrophils of two affected males in these kinships generated no chemiluminescence, whereas two of seven female relatives had intermediate values, and all nonaffected males had normal values. In the three families in which leukocytes were studied by nitroblue tetrazolium reduction, two populations of neutrophils were demonstrated for the female patients and/or their mothers. The wide phenotypic variability for clinical disease, evidence of two leukocyte populations in the patients or their mothers, and low but detectable leukocyte chemiluminescence in the affected females is consistent with the Lyon hypothesis of x-chromosome inactivation in these families. The findings suggest an x-linked inheritance in these females with chronic granulomatous disease.
Natural orifice transluminal endoscopic surgery gastrotomy closure in porcine explants with the Padlock-G clip using the Lock-It system
Authors: J. Romanelli, D. Desilets, D. Earle
Journal: Endoscopy (2010)

The success of transgastric surgery depends on reliable, secure closure of the gastrotomy. Few tests of the integrity of these closures have been published. This study aimed to determine whether a gastrotomy suitable for a NOTES procedure can be closed safely and effectively from within the stomach using a novel endoscopically placed device, the Padlock-G with the Lock-It delivery system.In a series of eight consecutive porcine gastric explants gastrotomy was performed in an ex vivo animal laboratory, the gastrotomy being closed with the Padlock-G followed by burst pressure testing after completion of the procedure. Gastrotomies were made in porcine explants. T-tags were placed on either side of the gastrotomy, and, with the T-tags pulled into an endoscopic cap, the Padlock-G was deployed. Gastric transmural pressure gradients at bursting of these closures were measured during insufflation of the explanted stomachs with a high-pressure insufflator.The mean burst pressure of the gastrotomy closures was 68.0 mm Hg (range: 45 - 107 mm Hg). All of the stomachs ultimately ruptured at the closure sites, with the exception of the stomach that ruptured at the highest value (107 mm Hg), which ruptured at a site approximately 5 cm away from the closure site. All of the closures were accomplished in 30 minutes or less.The Padlock-G clip provides a secure gastric closure for natural-orifice surgery.