tbuckley/cabot-search huggingface dataset:
Does This Patient Have Ventilator-Associated Pneumonia?
Authors: Michael Klompas
Journal: JAMA (2007)

Ventilator-associated pneumonia (VAP) is a common and serious nosocomial infection. Accurate, timely diagnosis enables affected patients to receive appropriate therapy and avoids mistreatment of patients having other conditions.To review the published medical literature describing the precision and accuracy of clinical, radiographic, and laboratory data to diagnose bacterial VAP relative to a histological gold standard.English-language articles identified by a structured search strategy using MEDLINE (January 1966-October 31, 2006) and Google Scholar. Additional articles were identified through the reference lists of studies and review papers identified by the search strategy.Included studies described clinical findings associated with VAP in 25 or more patients receiving mechanical ventilation who subsequently underwent pulmonary biopsy or autopsy. Fourteen studies describing clinical findings in 655 patients met inclusion criteria.Data were abstracted onto a structured form, allowing calculation of the likelihood ratios (LRs) for each sign or combination of findings.The presence or absence of fever, abnormal white blood cell count, or purulent pulmonary secretions do not substantively alter the probability of VAP. However, the combination of a new radiographic infiltrate with at least 2 of fever, leukocytosis, or purulent sputum increases the likelihood of VAP (summary LR, 2.8; 95% confidence interval, 0.97-7.9). The absence of a new infiltrate on a plain chest radiograph lowers the likelihood of VAP (summary LR, 0.35; 95% confidence interval, 0.14-0.87). Fewer than 50% neutrophils on cell count analysis of lower pulmonary secretions makes VAP unlikely (LR range, 0.05-0.10).Routine bedside evaluation coupled with radiographic information provides suggestive but not definitive evidence that VAP is present or absent. Given the severity of VAP and the frequency of serious conditions that can mimic VAP, clinicians should be ready to consider additional tests that provide further evidence for VAP or that establish another diagnosis.
Hoosier Oncology Group Randomized Phase II Study of Docetaxel, Vinorelbine, and Estramustine in Combination in Hormone-Refractory Prostate Cancer with Pharmacogenetic Survival Analysis
Authors: Noah M. Hahn, Sharon Marsh, William Fisher, Robert Langdon, Robin Zon, Mark Browning, Cynthia S. Johnson, Tiffany J. Scott-Horton, Lang Li, Howard L. McLeod, Christopher J. Sweeney
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To determine the safety and efficacy of two docetaxel doublets in hormone-refractory prostate cancer (HRPC) patients and to examine the prognostic role of polymorphisms in host genes important to docetaxel metabolism and transport. Experimental Design: Sixty-four chemotherapy-naive patients with HRPC were randomized to docetaxel and vinorelbine (D, 20 mg/m2 i.v. days 1 and 8; V, 25 mg/m2 i.v. days 1 and 8) or docetaxel and estramustine phosphate (D, 60-70 mg/m2 i.v. day 1; E, 280 mg oral thrice daily days 1-5) administered q21d. Primary end point was clinically significant toxicity. A pharmacogenetic analysis of host genes was done in patients who received at least one cycle of docetaxel therapy. Results: Grade 3/4 toxicity occurred in 15.6% of DV patients and in 28.6% DE patients. Neither arm exceeded the threshold of clinically significant toxicity. In the DV arm, objective response rate was 33%, prostate-specific antigen response rate was 20%, and median survival was 16.2 months. In the DE arm, objective response rate was 67%, prostate-specific antigen response rate was 43%, and median survival was 19.7 months. Pharmacogenetic analyses showed a significant association between survival beyond 15 months and the ABCG2 421 C&amp;gt;A (Q141K) polymorphism compared with the wild-type (C/C) genotype (66% versus 27%; P = 0.05). Conclusions: DV and DE doublets are active with a tolerable toxicity profile in patients with HRPC; however, efficacy does not seem superior to standard single-agent docetaxel. The ABCG2 421 C&amp;gt;A (Q141K) polymorphism may be an important predictor of response and survival in HRPC patients treated with docetaxel-based chemotherapy.
Protective effects of sialylated oligosaccharides in immune complex-induced acute lung injury.
Authors: M S Mulligan, J B Lowe, R D Larsen, J Paulson, Z L Zheng, S DeFrees, K Maemura, M Fukuda, P A Ward
Journal: The Journal of Experimental Medicine (1993)

Using sialyl Lewisx (SLX) oligosaccharides derived from fucosyl transferase-expressing cells or generated synthetically, the ability of these compounds to protect against acute lung damage after deposition of immunoglobulin (Ig)G or IgA immune complexes has been determined. The synthetic compounds were tetra- and pentasaccharide derivates of SLX as well as the nonfucosylated forms of SLX as controls. In the IgG immune complex model of lung injury, which is E-selectin dependent, SLX preparations provided dose-dependent protective effects, as assessed by changes in lung vascular permeability and hemorrhage. Protective effects were associated with diminished tissue accumulation of neutrophils in lungs (as assessed by myeloperoxidase). Morphological assessment revealed reduced physical contact of neutrophils with the pulmonary vascular endothelium and reduced tissue accumulation of neutrophils. In the model of IgA immune complex-induced lung injury, which does not involve participation of neutrophils and is independent of the requirement for E-selectin, SLX preparations were not protective. These data suggest that, in neutrophil-mediated and E-selectin-dependent lung injury, SLX preparations provide significant, protective effects against inflammatory vascular injury. The ability to achieve antiinflammatory outcomes in vivo with appropriate oligosaccharides suggests a new approach to the blocking of acute inflammatory responses.
Explaining norms and norms explained
Authors: David Danks, Frederick Eberhardt
Journal: Behavioral and Brain Sciences (2009)

Abstract Oaksford &amp; Chater (O&amp;C) aim to provide teleological explanations of behavior by giving an appropriate normative standard: Bayesian inference. We argue that there is no uncontroversial independent justification for the normativity of Bayesian inference, and that O&amp;C fail to satisfy a necessary condition for teleological explanations: demonstration that the normative prescription played a causal role in the behavior's existence.
Long­term noninvasive ventilation in children and adolescents with neuromuscular disorders
Authors: U. Mellies, R. Ragette, C. Dohna Schwake, H. Boehm, T. Voit, H. Teschler
Journal: European Respiratory Journal (2003)

The aim of the current study was to investigate the long­term impact of nocturnal noninvasive (positive­pressure) ventilation (NIV) on sleep, sleep­disordered breathing (SDB) and respiratory function in children and adolescents with progressive neuromuscular disorders (NMD). Thirty patients (12.3±4.1 yrs) with various inherited NMD were treated with NIV for ventilatory insufficiency (n=14) or symptomatic SDB (n=16). Patients were prospectively followed with sleep studies, spirometry and peak inspiratory muscle pressure. Ten patients were studied before and after 3 nights withdrawal from NIV. NIV normalised nocturnal gas exchange in all patients and diurnal gas exchange in patients with ventilatory insufficiency. The effects persisted over 25.3±12.7 months. Nocturnal transcutaneous partial pressure of carbon dioxide improved from (baseline versus latest control) 7.1±1.3 to 5.5±0.6 kPa (53.7±9.9 to 41.6±4.8 mmHg), diurnalcarbon dioxide arterial tension from 6.3±1.6 to 5.4±0.5 kPa (47.5±11.9 to 40.6±3.6 mmHg). NIV improved respiratory disturbance index, arousals from sleep, nocturnal heart rate and sleep architecture. Vital capacity decreased in five adolescents with Duchenne muscular dystrophy −183±111 mL·yr −1 but remained stable in 25 children with other conditions (8±78 mL·yr −1 ). Three nights withdrawal of NIV in 10 previously stable patients resulted in prompt deterioration of SDB and gas exchange back to baseline but could be instantly normalised by resumption of NIV. Noninvasive (positive­pressure) ventilation has favourable long­term impact on nocturnal and diurnal gas exchange and sleep and in patients with non­Duchenne neuromuscular disorders on vital capacity as well. It is indicated in children and adolescents with symptomatic sleep­disordered breathing or ventilatory insufficiency due to neuromuscular disorders.
Diastolic Intracellular Calcium-Membrane Voltage Coupling Gain and Postshock Arrhythmias
Authors: Mitsunori Maruyama, Boyoung Joung, Liang Tang, Tetsuji Shinohara, Young-Keun On, Seongwook Han, Eue-Keun Choi, Dae-Hyeok Kim, Mark J. Shen, James N. Weiss, Shien-Fong Lin, Peng-Sheng Chen
Journal: Circulation Research (2009)

Recurrent ventricular arrhythmias after initial successful defibrillation are associated with poor clinical outcome.We tested the hypothesis that postshock arrhythmias occur because of spontaneous sarcoplasmic reticulum Ca release, delayed afterdepolarization (DAD), and triggered activity (TA) from tissues with high sensitivity of resting membrane voltage (V(m)) to elevated intracellular calcium (Ca(i)) (high diastolic Ca(i)-voltage coupling gains).We simultaneously mapped Ca(i) and V(m) on epicardial (n=14) or endocardial (n=14) surfaces of Langendorff-perfused rabbit ventricles. Spontaneous Ca(i) elevation (SCaE) was noted after defibrillation in 32% of ventricular tachycardia/ventricular fibrillation at baseline and in 81% during isoproterenol infusion (0.01 to 1 micromol/L). SCaE was reproducibly induced by rapid ventricular pacing and inhibited by 3 mumol/L of ryanodine. The SCaE amplitude and slope increased with increasing pacing rate, duration, and dose of isoproterenol. We found TAs originating from 6 of 14 endocardial surfaces but none from epicardial surfaces, despite similar amplitudes and slopes of SCaEs between epicardial and endocardial surfaces. This was because DADs were larger on endocardial surfaces as a result of higher diastolic Ca(i)-voltage coupling gain, compared to those of epicardial surfaces. Purkinje-like potentials preceded TAs in all hearts studied (n=7). I(K1) suppression with CsCl (5 mmol/L, n=3), BaCl(2) (3 micromol/L, n=3), and low extracellular potassium (1 mmol/L, n=2) enhanced diastolic Ca(i)-voltage coupling gain and enabled epicardium to also generate TAs.Higher diastolic Ca(i)-voltage coupling gain is essential for genesis of TAs and may underlie postshock arrhythmias arising from Purkinje fibers. I(K)(1) is a major factor that determines the diastolic Ca(i)-voltage coupling gain.
Multidisciplinary Management of Focal Nodular Hyperplasia in Children
Authors: Gezzer Ortega, Mitchell Price, Shelly Choo, Seth D. Goldstein, Dylan Stewart, Fizan Abdullah
Journal: JAMA Surgery (2013)

Nonoperative management of focal nodular hyperplasia (FNH) is an accepted paradigm in adults, but current management strategies for children vary substantially between institutions. We reviewed medical records at Johns Hopkins Hospital between January 1, 1998, and December 31, 2008, to investigate the diagnosis, treatment, and outcome of pediatric patients with a pathologic diagnosis of FNH to provide additional data to help formulate management guidelines for this disease. Ten pediatric patients were identified as having a pathologic diagnosis of FNH, either by biopsy sample (n = 5) or hepatic resection (n = 5). The mean age of the patients was 12.1 years, and most were female (n = 7). Mean tumor size was 5.7 cm (range, 0.8-13 cm). Four of 5 patients whose FNH was diagnosed by biopsy alone developed no sequelae, and 1 patient eventually required surgery for mass effect. Patients with either large lesions (≥5 cm) or symptoms were referred for resection. Observational management of small lesions that can be confidently diagnosed as FNH appears to be safe and appropriate. Surgical resection should be reserved for large or symptomatic lesions amenable to resection.
The Monoclonal Antibody nBT062 Conjugated to Cytotoxic Maytansinoids Has Selective Cytotoxicity Against CD138-Positive Multiple Myeloma Cells<i>In vitro</i>and<i>In vivo</i>
Authors: Hiroshi Ikeda, Teru Hideshima, Mariateresa Fulciniti, Robert J. Lutz, Hiroshi Yasui, Yutaka Okawa, Tanyel Kiziltepe, Sonia Vallet, Samantha Pozzi, Loredana Santo, Giulia Perrone, Yu-Tzu Tai, Diana Cirstea, Noopur S. Raje, Christoph Uherek, Benjamin Dälken, Silke Aigner, Frank Osterroth, Nikhil Munshi, Paul Richardson, Kenneth C. Anderson
Journal: Clinical Cancer Research (2009)

Abstract Purpose: We investigated the antitumor effect of murine/human chimeric CD138-specific monoclonal antibody nBT062 conjugated with highly cytotoxic maytansinoid derivatives against multiple myeloma (MM) cells in vitro and in vivo. Experimental Design: We examined the growth inhibitory effect of BT062-SPDB-DM4, BT062-SMCC-DM1, and BT062-SPP-DM1 against MM cell lines and primary tumor cells from MM patients. We also examined in vivo activity of these agents in murine MM cell xenograft model of human and severe combined immunodeficient (SCID) mice bearing implant bone chips injected with human MM cells (SCID-hu model). Results: Anti-CD138 immunoconjugates significantly inhibited growth of MM cell lines and primary tumor cells from MM patients without cytotoxicity against peripheral blood mononuclear cells from healthy volunteers. In MM cells, they induced G2-M cell cycle arrest, followed by apoptosis associated with cleavage of caspase-3, caspase-8, caspase-9, and poly(ADP-ribose) polymerase. Nonconjugated nBT062 completely blocked cytotoxicity induced by nBT062-maytansinoid conjugate, confirming that specific binding is required for inducing cytotoxicity. Moreover, nBT062-maytansinoid conjugates blocked adhesion of MM cells to bone marrow stromal cells. The coculture of MM cells with bone marrow stromal cells protects against dexamethasone-induced death but had no effect on the cytotoxicity of immunoconjugates. Importantly, nBT062-SPDB-DM4 and nBT062-SPP-DM1 significantly inhibited MM tumor growth in vivo and prolonged host survival in both the xenograft mouse models of human MM and SCID-hu mouse model. Conclusion: These results provide the preclinical framework supporting evaluation of nBT062-maytansinoid derivatives in clinical trials to improve patient outcome in MM.
FAT METABOLISM IN NEPHRITIS
Authors: A. Hiller, G. C. Linder, C. Lundsgaard, D. D. Van Slyke
Journal: The Journal of Experimental Medicine (1924)

Determinations of the plasma lipoids and of the respiratory quotient and total metabolism (Tissot method) have been performed with nephritics and normal subjects before and after they ingested fat in the proportion of 1 gm. per kilo body weight. After fat ingestion a greater increase of fatty acids and lecithin was noted in the plasma of nephritics with initially high blood lipoids than in the plasma of normal subjects or of nephritics without constant lipemia. In cholesterol no differences were found. The nephritic patients with constant lipemia were able to burn fat as efficiently as normal individuals. The accumulation of fat in their blood may be due to a disturbance in the mechanism for transferring lipoids from the blood to the tissue depots.
No clear effect of postoperative radiotherapy on survival of breast cancer patients with one to three positive nodes: a population-based study
Authors: A.E. Nordenskjöld, H. Fohlin, P. Albertsson, L.G. Arnesson, C. Chamalidou, Z. Einbeigi, E. Holmberg, B. Nordenskjöld, P. Karlsson
Journal: Annals of Oncology (2015)
First report on a prospective trial with yttrium-90–labeled ibritumomab tiuxetan (Zevalin) in primary CNS lymphoma
Authors: Sofiane Maza, Philipp Kiewe, Dieter L. Munz, Agnieszka Korfel, Bernd Hamm, Kristoph Jahnke, Eckhard Thiel
Journal: Neuro-Oncology (2008)

Most patients with primary CNS lymphoma (PCNSL) relapse after primary therapy. Standard salvage treatment has not yet been established in PCNSL. Anti-CD20 immunotherapy has expanded treatment options in systemic B-cell lymphoma; however, its use is limited by reconstitution of the blood–brain barrier after tumor shrinkage. The aim of this phase II trial was to evaluate the therapeutic efficacy, toxicity, and biodistribution of yttrium-90 (90Y) ibritumomab tiuxetan in PCNSL. Ten patients with relapsed PCNSL were included in a phase II trial and treated with the 90Y-labeled anti-CD20 antibody ibritumomab tiuxetan. Nine patients actually received the planned radioimmunotherapy. In six patients, biodistribution of the antibody was measured by indium-111 (111In) ibritumomab tiuxetan whole-body scans and single-photon-emission CT (SPECT) of the brain. All patients were evaluated for toxicity and response at least 4 weeks after therapy. Four patients responded: one patient had a complete response lasting 30+ months, and three patients had short-lived responses of ⩽4 weeks. Five patients progressed, and one patient did not receive treatment due to an infection prior to 90Y-antibody administration. Target accumulation of the antibody was demonstrated in four of the six patients examined by SPECT imaging with 111In ibritumomab tiuxetan. All patients experienced grade 3/4 hematotoxicity but no acute neurotoxicity. Penetration of a therapeutic antibody into PCNSL and significant clinical activity was shown. Because of limited response duration and considerable hematotoxicity, future investigations should focus on a multimodal approach with additional chemotherapy and preferably autologous stem cell support.
Sensory prediction as a role for the cerebellum
Authors: R. C. Miall, M. Malkmus, E. M. Robertson
Journal: Behavioral and Brain Sciences (1996)

We suggest that the cerebellum generates sensory or "state" estimates based on outgoing motor commands and sensory feedback. Thus, it is not a motor pattern generator (HOUK et al.) but a predictive system which is intimately involved in motor behavior. This theory may explain the sensitivity of the climbing fibers to both unexpected external events and motor errors (SIMPSON et al.), and we speculate that unusual biophysical properties of the inferior olive might allow the cerebellum to develop multiple asynchronous sensory estimates, [HOUK et al.; SIMPSON et al.; THACH]
Reduction of Cardiovascular Events by Simvastatin in Nondiabetic Coronary Heart Disease Patients With and Without the Metabolic Syndrome
Authors: Kalevi Pyörälä, Christie M. Ballantyne, Barry Gumbiner, Michael W. Lee, Arvind Shah, Michael J. Davies, Yale B. Mitchel, Terje R. Pedersen, John Kjekshus
Journal: Diabetes Care (2004)

To assess the effect of simvastatin treatment on the risk of cardiovascular events in nondiabetic patients with coronary heart disease (CHD) with and without the metabolic syndrome, as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP-III).Subgroup analyses were performed on data from 3933 nondiabetic patients with clinically established CHD, serum total cholesterol level 5.5-8.0 mmol/l, and serum triglyceride level <or=2.5 mmol/l who were participating in the Scandinavian Simvastatin Survival Study (4S), a randomized, placebo-controlled trial. End points were total mortality, coronary mortality, major CHD event, myocardial revascularization, any CHD event, stroke, and any atherosclerotic event.Over the 5.4-year median follow-up period, simvastatin produced similar changes in serum lipid levels in 893 patients with the metabolic syndrome and in 3040 patients without the metabolic syndrome. The relative risks of main end points in simvastatin-treated patients compared with placebo-treated patients with the metabolic syndrome were as follows: total mortality 0.54 (95% CI 0.36-0.82), coronary mortality 0.39 (0.23-0.65), major CHD event 0.59 (0.45-0.77), and any atherosclerotic event 0.69 (0.56-0.84). The corresponding RRs in patients without the metabolic syndrome were 0.72 (0.56-0.91), 0.62 (0.45-0.84), 0.71 (0.61-0.82), and 0.76 (0.68-0.85).Nondiabetic CHD patients with or without the metabolic syndrome realize from simvastatin treatment a similar, substantial relative reduction in the risk of cardiovascular events. The absolute benefit may be greater in patients with the metabolic syndrome because they are at a higher absolute risk.
Radiogenic Breast Cancer Effects of Mammographic Screening
Authors: J K Gohagan, W P Darby, E L Spitznagel, B S Monsees, A E Tome
Journal: JNCI Journal of the National Cancer Institute (1986)

The radiocarcinogenic implications of published breast-screening policies were compared. With the use of radioepidemiologic data published recently by the National Institutes of Health, expected excess breast cancers were projected. With a base-line mammogram at age 35 and annual mammography after age 40, as few as 150 or as many as 1,000 radiogenic breast cancers were projected for a screening population of 1 million women, depending on the mammographic system employed and the screening schedule.
High plasma level of nucleocapsid-free envelope glycoprotein-positive lipoproteins in hepatitis C patients
Authors: Caroline Scholtes, Christophe Ramière, Dominique Rainteau, Laure Perrin-Cocon, Claude Wolf, Lydie Humbert, Martine Carreras, Aurélie Guironnet-Paquet, Fabien Zoulim, Ralf Bartenschlager, Vincent Lotteau, Patrice André, Olivier Diaz
Journal: Hepatology (2012)

Hepatitis C virus (HCV) particles associate viral and lipoprotein moieties to form hybrid lipoviral particles (LVPs). Cell culture-produced HCV (HCVcc) and ex vivo-characterized LVPs primarily differ by their apolipoprotein (apo) B content, which is low for HCVcc, but high for LVPs. Recombinant nucleocapsid-free subviral LVPs are assembled and secreted by apoB-producing cell lines. To determine whether such subviral particles circulate in HCV-infected individuals, LVPs complexed with immunoglobulin were precipitated with protein A from low-density plasma fractions of 36 hepatitis C patients, and their lipid content, apolipoprotein profile, and viral composition were determined. HCV RNA in LVPs was quantified and molar ratios of apoB and HCV genome copy number were calculated. LVPs lipidome from four patients was determined via electrospray ionization/tandem mass spectrometry. Protein A-purified LVPs contained at least the envelope glycoprotein E2 and E2-specific antibodies. LVPs were present in every patient and were characterized by high lipid content, presence of apolipoproteins characteristic of triglyceride-rich lipoproteins (TRLs), HCV RNA, and viral glycoprotein. Importantly, save for four patients, LVPs fractions contained large amounts of apoB, with on average more than 1 × 10(6) apoB molecules per HCV RNA genome. Because there is one apoB molecule per TRL, this ratio suggested that most LVPs are nucleocapsid-free, envelope glycoprotein-containing subviral particles. LVPs and TRLs had similar composition of triacylglycerol and phospholipid classes.LVPs are a mixed population of particles, comprising predominantly subviral particles that represent a distinct class of modified lipoproteins within the TRL family.