tbuckley/cabot-search huggingface dataset:
Sedation and Analgesia in the Mechanically Ventilated Patient
Authors: Shruti B. Patel, John P. Kress
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Sedation and analgesia are important components of care for the mechanically ventilated patient in the intensive care unit (ICU). An understanding of commonly used medications is essential to formulate a sedation plan for individual patients. The specific physiological changes that a critically ill patient undergoes can have direct effects on the pharmacology of drugs, potentially leading to interpatient differences in response. Objective assessments of pain, sedation, and agitation have been validated for use in the ICU for assessment and titration of medications. An evidence-based strategy for administering these drugs can lead to improvements in short- and long-term outcomes for patients. In this article, we review advances in the field of ICU sedation to provide an up-to-date perspective on management of the mechanically ventilated ICU patient.
Cancer-Specific Outcomes Among Young Adults Without Health Insurance
Authors: Ayal A. Aizer, Benjamin Falit, Mallika L. Mendu, Ming-Hui Chen, Toni K. Choueiri, Karen E. Hoffman, Jim C. Hu, Neil E. Martin, Quoc-Dien Trinh, Brian M. Alexander, Paul L. Nguyen
Journal: Journal of Clinical Oncology (2014)

The Patient Protection and Affordable Care Act (ACA) will likely improve insurance coverage for most young adults, but subsets of young adults in the United States will face significant premium increases in the individual market. We examined the association between insurance status and cancer-specific outcomes among young adults.We used the SEER program to identify 39,447 patients age 20 to 40 years diagnosed with a malignant neoplasm between 2007 and 2009. The association between insurance status and stage at presentation, employment of definitive therapy, and all-cause mortality was assessed using multivariable logistic or Cox regression, as appropriate.Patients who were uninsured were more likely to be younger, male, nonwhite, and unmarried than patients who were insured and were also more likely to be from regions of lower income, education, and population density (P < .001 in all cases). After adjustment for pertinent confounding variables, an association between insurance coverage and decreased likelihood of presentation with metastatic disease (odds ratio [OR], 0.84; 95% CI, 0.75 to 0.94; P = .003), increased receipt of definitive treatment (OR, 1.95; 95% CI, 1.52 to 2.50; P < .001), and decreased death resulting from any cause (hazard ratio, 0.77; 95% CI, 0.65 to 0.91; P = .002) was noted.The improved coverage fostered by the ACA may translate into better outcomes among most young adults with cancer. Extra consideration will need to be given to ensure that patients who will face premium increases in the individual market can obtain insurance coverage under the ACA.
The simultaneous comparison of acetylene or carbon dioxide flux as a measure of effective pulmonary blood flow in children
Authors: M Rosenthal, A Bush
Journal: European Respiratory Journal (1997)

Both acetylene (Ac) and carbon dioxide can be used to measure effective pulmonary blood flow (Q'eff) noninvasively. They are safe and reasonably accurate in adults during rest and exercise, but there have been no simultaneous comparisons in children. One hundred and six healthy children (55 males and 51 females, aged 8-17 yrs) were studied using an Innovision quadrupole mass spectrometer. They all underwent five rebreathing manoeuvres at rest, and then single measurements were again taken after 9 min of bicycle exercise. Mixed venous CO2 levels were calculated either by a linear (L) or curvilinear (C) extrapolation method. At rest, the coefficients of variation for Q'eff were Ac 8%, L 20%, and C 16% (p&lt;0.001). The median resting values were: Ac 3.2 (95% confidence interval (95% CI) 3.1-3.4) L 5.1 (95 % CI 4.6-5.4) and C 4.7 (95 % CI 4.3-5.1) L x min(-1) x m(-2), (p&lt;0.001). Compared to Ac, only 14 and 17% of L and C values, respectively, were +/-0.5 L x min(-1) x m(-2), whilst 41 and 29%, respectively were more than +/-2 L x min(-1) x m(-2). During exercise, median values were: Ac 6.7 (95% CI 6.3-7.0); L 8.0 (95% CI 7.3-8.4); and C 7.2 (95% CI 6.5-7.9) L x min(-1) x m(-2). L was significantly greater than C (p&lt;0.001), but C was similar to Ac (p=0.06). More than 50% of L and C values could not be calculated for various reasons, whereas all 106 Ac values could be calculated. Neither carbon dioxide method is sufficiently reliable to be used in children in a clinical setting. Acetylene was safe, reliable, accurate and preferred.
Inhibitory Effect of Epinephrine on Insulin-stimulated Glucose Uptake by Rat Skeletal Muscle
Authors: Jean-Louis Chiasson, Hisataka Shikama, David T. W. Chu, John H. Exton
Journal: Journal of Clinical Investigation (1981)

The effect of epinephrine on basal and insulin-stimulated glucose uptake in perfused hindlimbs of fed rats was studied. Insulin increased glucose uptake in a dose-dependent manner from a basal value of 1.5+/-0.3 up to a maximum value of 5.3+/-0.9 mumol/min per 100 g with 6 nM (1 m U/ml). Epinephrine at 10 nM and 0.1 muM also increased glucose uptake to 2.6+/-0.1 and 3.1+/-0.1 mumol/min per 100 g, respectively. These same concentrations of epinephrine, however, suppressed the insulin-stimulated glucose uptake to 3.2+/-0.3 mumol/min per 100 g. Both the stimulatory and inhibitory effects of epinephrine on glucose uptake were completely reversed by propranolol, but were not significantly altered by phentolamine. Uptake of 3-O-methylglucose and 2-deoxyglucose into thigh muscles of the perfused hindlimbs was stimulated fivefold by insulin, but was unaffected by epinephrine. Epinephrine also did not inhibit the stimulation of uptake by insulin. Epinephrine decreased the phosphorylation of 2-deoxyglucose, however, and caused the intracellular accumulation of free glucose. These last two effects were more prominent in the presence of insulin. Whereas epinephrine caused large rises in glucose-6-P and fructose-6-P, insulin did not alter the concentration of these metabolites either in the absence or presence of epinephrine.THESE DATA INDICATE THAT: (a) epinephrine has a stimulatory effect on glucose uptake by perfused rat hindlimbs that does not appear to be exerted on skeletal muscle; (b) epinephrine does not affect hexose transport in skeletal muscle; (c) epinephrine inhibits insulin-stimulated glucose uptake in skeletal muscle by inhibiting glucose phosphorylation. It is hypothesized that the inhibition of glucose phosphorylation is due to the stimulation of glycogenolysis, which leads to the accumulation of hexose phosphates, which inhibit hexokinase.
Human Leukocyte Antigen-A2–Restricted CTL Responses to Mutated BRAF Peptides in Melanoma Patients
Authors: Rajasekharan Somasundaram, Rolf Swoboda, Laura Caputo, Laszlo Otvos, Barbara Weber, Patricia Volpe, Patricia van Belle, Susan Hotz, David E. Elder, Francesco M. Marincola, Lynn Schuchter, DuPont Guerry, Brian J. Czerniecki, Dorothee Herlyn
Journal: Cancer Research (2006)

Abstract Mutated BRAF (BRAFV600E) is a potential immunotherapeutic target for melanoma because of its tumor specificity and expression in the majority of these lesions derived from different patients. BRAFV600E is expressed intracellularly and not on the cell surface, therefore providing a target for T cells but not B cells. Demonstration of patients' T cell responses to BRAFV600E would suggest the feasibility of active specific immunotherapy targeting the mutation in these patients. In the present study, BRAFV600E peptides with putative binding sites for human leukocyte antigen (HLA)-A2 were used to stimulate T lymphocytes of HLA-A2–positive melanoma patients. Four of five patients with BRAFV600E-positive lesions showed lymphoproliferative responses to BRAFV600E peptide stimulation. These responses were specific for the mutated epitope and HLA-A2 was restricted in three patients. Lymphocytes from these three patients were cytotoxic against HLA-A2–matched BRAFV600E-positive melanoma cells. None of the four patients with BRAFV600E-negative lesions and none of five healthy donors had lymphoproliferative responses specific for the mutated epitope. The high prevalence (∼50%) of HLA-A2 among melanoma patients renders HLA-A2–restricted BRAFV600E peptides attractive candidate vaccines for these patients. (Cancer Res 2006; 66(6): 3287-93)
Information Processing in the Primate Retina: Circuitry and Coding
Authors: G.D. Field, E.J. Chichilnisky
Journal: Annual Review of Neuroscience (2007)

The function of any neural circuit is governed by connectivity of neurons in the circuit and the computations performed by the neurons. Recent research on retinal function has substantially advanced understanding in both areas. First, visual information is transmitted to the brain by at least 17 distinct retinal ganglion cell types defined by characteristic morphology, light response properties, and central projections. These findings provide a much more accurate view of the parallel visual pathways emanating from the retina than do previous models, and they highlight the importance of identifying distinct cell types and their connectivity in other neural circuits. Second, encoding of visual information involves significant temporal structure and interactions in the spike trains of retinal neurons. The functional importance of this structure is revealed by computational analysis of encoding and decoding, an approach that may be applicable to understanding the function of other neural circuits.
p53 Enhances Gefitinib-Induced Growth Inhibition and Apoptosis by Regulation of Fas in Non–Small Cell Lung Cancer
Authors: Jin Kyung Rho, Yun Jung Choi, Baek-Yeol Ryoo, Im II Na, Sung Hyun Yang, Cheol Hyeon Kim, Jae Cheol Lee
Journal: Cancer Research (2007)

Treatment with gefitinib, a specific inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK), has resulted in dramatic responses in some patients with non-small cell lung cancer (NSCLC). Most patients who respond to gefitinib have EGFR-TK mutations; however, >10% of patients with EGFR-TK mutations do not respond. Similarly, some patients without EGFR-TK mutations respond to this drug, suggesting that other factors determine sensitivity to gefitinib. Aberrations of the tumor suppressor gene p53 are frequently associated with drug resistance. In this study, we investigated the role of p53 in growth-inhibitory and apoptotic effects of gefitinib in the human NSCLC cell lines NCI-H1299 and A549, which have no EGFR-TK mutations. NCI-H1299 cells, which had a p53-null genotype, were more resistant to gefitinib compared with A549 cells, which were wild-type p53 (IC(50), 40 micromol/L in NCI-H1299 and 5 micromol/L in A549). Treatment of A549 with gefitinib resulted in the translocation of p53 from cytosol to nucleus and the up-regulation of Fas, which was localized to the plasma membrane. In the stable H1299 cell line with tetracycline-inducible p53 expression, induced p53 enhanced growth inhibition and apoptosis by gefitinib through the up-regulation of Fas and restoration of caspase activation. A caspase inhibitor, Z-VAD-fmk, reduced these effects. Conversely, inhibition of p53 using antisense oligonucleotide in A549 caused a significant decrease in apoptosis by gefitinib and down-regulation of Fas under the same conditions. In conclusion, p53 may play a role in determining gefitinib sensitivity by regulating Fas expression in NSCLC.
Frederic John Aumonier
Authors: D. Lacy
Journal: BMJ (2003)

Former histologist and venereologist London (b 1911; q Guy's Hospital, London 1944; DA), d 6 June 2003.

John Aumonier studied zoology at University College London before starting medicine at Guy's in 1939. After qualifying he became an assistant medical officer at Monmouthshire County Mental Hospital and was briefly a lecturer in zoology at Southampton before becoming a lecturer in histology at Middlesex Hospital Medical School in 1948. In 1953 he became a histologist at St Bartholomew's Hospital Medical College, where he and the professor of anatomy explored intricate and poorly understood internal features of large mammals. He left St Bartholomew's in 1972 to pursue a career in venereology, working in many clinics, including at St Mary's, Paddington, and Pentonville prison. He was an enthusiastic sailor. Predeceased by his wife, Nell, he leaves two daughters and four grandchildren.
Prospective Validation of <i>HLA-DRB1</i>*<i>07:01</i> Allele Carriage As a Predictive Risk Factor for Lapatinib-Induced Liver Injury
Authors: Daniel J. Schaid, Colin F. Spraggs, Shannon K. McDonnell, Laura R. Parham, Charles J. Cox, Bent Ejlertsen, Dianne M. Finkelstein, Erica Rappold, Joan Curran, Lon R. Cardon, Paul E. Goss
Journal: Journal of Clinical Oncology (2014)

Liver injury is a serious adverse event leading to permanent discontinuation of lapatinib in affected patients. This study aimed to validate previously associated major histocompatibility complex (MHC) variants as predictors of risk of liver injury by using a large, randomized, placebo-controlled trial of lapatinib in human epidermal growth factor receptor 2-positive, early-stage breast cancer (Tykerb Evaluation After Chemotherapy [TEACH]: Lapatinib Versus Placebo In Women With Early-Stage Breast Cancer).The frequency of ALT elevation cases was compared among four MHC variants in 1,194 patients randomly assigned to lapatinib. Cumulative ALT elevation time courses during treatment were also compared between carriers and noncarriers of specified MHC variants.In lapatinib-treated patients, there was a significant difference in ALT case incidence between HLA carriers and noncarriers. The highly correlated alleles HLA-DRB1*07:01 and HLA-DQA1*02:01 (study frequency, 22.4%) were associated with ALT elevation (odds ratio, 14) between cases (n = 37) and controls (n = 1,071). These associations strengthened at higher ALT elevation thresholds and in Hy's Law cases. In lapatinib-treated patients, the overall risk for National Cancer Institute-Common Terminology Criteria for Adverse Events grade 3 ALT elevation (> 5× upper limit of normal) was 2.1%; HLA allele carriers had an increased risk of 7.7%; in noncarriers, risk was reduced to 0.5%, comparable to ALT elevation for all patients receiving placebo. The increase in ALT case incidence in the lapatinib arm showed no evidence of plateau during 1 year of lapatinib treatment.These results validate HLA-DRB1*07:01 allele carriage as a predictor of increased risk of lapatinib-induced liver injury and implicate an immune pathology. The HLA association could support clinical management of patients experiencing hepatotoxicity during lapatinib treatment.
The B Cell Receptor Itself Can Activate Complement to Provide the Complement Receptor 1/2 Ligand Required to Enhance B Cell Immune Responses In Vivo
Authors: Joerg Rossbacher, Mark J. Shlomchik
Journal: The Journal of Experimental Medicine (2003)

B cells express complement receptors (CRs) that bind activated fragments of C3 and C4. Immunized CR knockout (KO) mice have lower antibody titers and smaller germinal centers (GCs), demonstrating the importance of CR signals for the humoral immune response. CR ligands were thought to be generated via complement fixation mediated by preexisting “natural” IgM or early Ab from inefficiently activated B cells. This concept was recently challenged by a transgenic (Tg) mouse model that lacks circulating antibody but still retains membrane IgM (mIgM) and mounts normal immune responses. To test whether CR ligands could be generated by the B cell receptor (BCR) itself, we generated similar mice carrying a mutated mIgM that was defective in C1q binding. We found that B cells from such mutant mice do not deposit C3 on B cells upon BCR ligation, in contrast to B cells from mIgM mice. This has implications for the immune response: the mutant mice have smaller GCs than mIgM mice, and they are particularly deficient in the maintenance of the GC response. These results demonstrate a new BCR-dependent pathway that is sufficient and perhaps necessary to provide a CR1/2 ligand that promotes efficient B cell activation.
Lower limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon.
Authors: J V Jones, W Fitch, E T MacKenzie, S Strandgaard, A M Harper
Journal: Circulation Research (1976)

The effect of arterial hypertension on cerebral blood flow was studied by the intracarotid 133Xe clearance method in baboons. The arterial blood pressure was raised in gradual steps with angiotensin. Baboons with renal hypertension of 8-12 weeks duration were studied along with normotensive baboons. In initially normotensive baboons, cerebral blood flow remained constant until the mean arterial blood pressure had risen to the range of 140 to 154 mm Hg; thereafter cerebral blood flow increased with each rise in mean arterial blood pressure. In the chronically hypertensive baboons, cerebral blood flow remained constant until the mean arterial blood pressure had been elevated to the range of 155 to 169 mm Hg. Thus, in chronic hypertension it appears that there are adaptive changes in the cerebral circulation which may help to protect the brain from further increases in arterial blood pressure.
The Implications of Webster for Practicing Physicians
Authors: Ann E. Allen
Journal: JAMA (1989)

Writing under the auspices of the American College of Obstetricians and Gynecologists (ACOG), the authors assess the impact on physicians of the U.S. Supreme Court's decision in the Missouri abortion case Webster v. Reproductive Health Services (3 July 1989). They see Webster as having little immediate impact on physicians' practices except in Missouri, the only state to which the decision applies. Allen and Pearse predict that the long-range impact of Webster will be greater and more widespread as it opens the door to more extensive state regulation of abortion and other reproductive services. They argue that the prevention of unwanted pregnancy, not limiting access, is the way to reduce the abortion rate. They urge physicians to become involved in a public education campaign to further ACOG's goal of preventing unwanted pregnancies through encouraging sex education and family planning programs, contraceptive research, and wider advertising of contraceptives.
An exploration of the basis for patient complaints about the oldness of magazines in practice waiting rooms: cohort study
Authors: B. Arroll, S. Alrutz, S. Moyes
Journal: BMJ (2014)

To explore the basis for patient complaints about the oldness of most magazines in practice waiting rooms.Cohort study.Waiting room of a general practice in Auckland, New Zealand.87 magazines stacked into three mixed piles and placed in the waiting room: this included non-gossipy magazines (Time magazine, the Economist, Australian Women's Weekly, National Geographic, BBC History) and gossipy ones (not identified for fear of litigation). Gossipy was defined as having five or more photographs of celebrities on the front cover and most gossipy as having up to 10 such images.The magazines were marked with a unique number on the back cover, placed in three piles in the waiting room, and monitored twice weekly.Disappearance of magazines less than 2 months old versus magazines 3-12 months old, the overall rate of loss of magazines, and the rate of loss of gossipy versus non-gossipy magazines.47 of the 82 magazines with a visible date on the front cover were aged less than 2 months. 28 of these 47 (60%) magazines and 10 of the 35 (29%) older magazines disappeared (P=0.002). After 31 days, 41 of the 87 (47%, 95% confidence interval 37% to 58%) magazines had disappeared. None of the 19 non-gossipy magazines (the Economist and Time magazine) had disappeared compared with 26 of the 27 (96%) gossipy magazines (P<0.001). All 15 of the most gossipy magazines and none of the non-gossipy magazines [corrected] had disappeared by 31 days. The study was terminated at this point.General practice waiting rooms contain mainly old magazines. This phenomenon relates to the disappearance of the magazines rather than to the supply of old ones. Gossipy magazines were more likely to disappear than non-gossipy ones. On the grounds of cost we advise practices to supply old copies of non-gossipy magazines. A waiting room science curriculum is urgently needed.
Muscle force during an acute exacerbation in hospitalised patients with COPD and its relationship with CXCL8 and IGF-I
Authors: M A Spruit
Journal: Thorax (2003)

<b>Background:</b> Chronic obstructive pulmonary disease (COPD) is often associated with peripheral muscle weakness, which is caused by several factors. Acute exacerbations may contribute, but their impact on muscle force remains unclear. Correlations between peripheral muscle force and inflammatory and anabolic markers have never been studied in COPD. The effect of an acute exacerbation on quadriceps peak torque (QPT) was therefore studied in hospitalised patients, and the aforementioned correlations were examined in hospitalised and in stable patients. <b>Methods:</b> Lung function, respiratory and peripheral muscle force, and inflammatory and anabolic markers were assessed in hospitalised patients on days 3 and 8 of the hospital admission and 90 days later. The results on day 3 (n=34) were compared with those in clinically stable outpatients (n=13) and sedentary healthy elderly subjects (n=10). <b>Results:</b> Hospitalised patients had lowest mean (SD) QPT (66 (22)% predicted) and highest median (IQR) levels of systemic interleukin-8 (CXCL8, 6.1 (4.5 to 8.3) pg/ml). Insulin-like growth factor I (IGF-I) tended to be higher in healthy elderly subjects (p=0.09). QPT declined between days 3 and 8 in hospital (mean −5% predicted (95% CI −22 to 8)) and partially recovered 90 days after admission to hospital (mean 6% predicted (95% CI −1 to 23)). QPT was negatively correlated with CXCL8 and positively correlated with IGF-I and lung transfer factor in hospitalised and in stable patients. <b>Conclusions:</b> Peripheral muscle weakness is enhanced during an acute exacerbation of COPD. CXCL8 and IGF-I may be involved in the development of peripheral muscle weakness in hospitalised and in stable patients with COPD.
Gastropleural Fistula in a Patient With Recurrent Ovarian Cancer Receiving Combination Therapy With Carboplatin, Gemcitabine, and Bevacizumab
Authors: Thorsten Dohrmann, Asad Kutup, Sven Mahner, Volkmar Müller, Fritz Jaenicke, Jacob R. Izbicki, Yogesh K. Vashist
Journal: Journal of Clinical Oncology (2013)
First-line erlotinib and bevacizumab in patients with locally advanced and/or metastatic non-small-cell lung cancer: a phase II study including molecular imaging
Authors: A.-M. C. Dingemans, A.J. de Langen, V. van den Boogaart, J.T. Marcus, W.H. Backes, H.T.G.M. Scholtens, H. van Tinteren, O.S. Hoekstra, J. Pruim, B. Brans, F.B. Thunnissen, E.F. Smit, H.J.M. Groen
Journal: Annals of Oncology (2010)
Activity and safety of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomised phase 2 dose expansion trial
Authors: Karim Fizazi, Christophe Massard, Petri Bono, Robert Jones, Vesa Kataja, Nicholas James, Jorge A Garcia, Andrew Protheroe, Teuvo L Tammela, Tony Elliott, Leena Mattila, John Aspegren, Annamari Vuorela, Peter Langmuir, Mika Mustonen
Journal: The Lancet Oncology (2014)
Lipid transfer protein is involved in rhinoconjunctivitis and asthma produced by rice inhalation
Authors: Ernesto Enrique, Oussama Ahrazem, Joan Bartra, M. Dolores Latorre, José Vicente Castelló, José Antonio de Mateo, Erika Montoya, Tamim Malek, Domingo Barber, Gabriel Salcedo
Journal: Journal of Allergy and Clinical Immunology (2005)