tbuckley/cabot-search huggingface dataset:
Abstract P2-16-01: A randomized, phase II, multicenter, double-blind, placebo-controlled trial evaluating onartuzumab with or without bevacizumab in combination with weekly paclitaxel in locally recurrent or metastatic triple-negative breast cancer (TNBC)
Authors: V Dieras, D Yardley, G Romieu, V Valero, S Isakoff, H Koeppen, H Thurm, M Teng, M Campone, S Mocci
Journal: Cancer Research (2013)

Abstract Background: Dysregulation of the hepatocyte growth factor (HGF)/MET pathway has been observed in many malignancies. In patients with TNBC, overexpression of MET has been shown to be associated with poor prognosis. Onartuzumab (MetMAb) is a recombinant, humanized, monovalent, monoclonal antibody directed against MET, which selectively blocks ligand binding and subsequent HGF activation. A recent phase 2 trial demonstrated improved progression-free survival (PFS) and overall survival (OS) when onartuzumab was added to erlotinib for patients with MET 2+/3+ non-small-cell lung cancer (NSCLC). Methods: Patients with locally recurrent or metastatic TNBC who had received 0 or 1 prior therapies for metastatic disease were enrolled, provided tumor sample, and randomized (1:1:1) to receive paclitaxel (P) + bevacizumab (B) + onartuzumab (O); P+O; or P+B. Dosing regimens were given IV q4w: P 90 mg/m2 d1, 8 &amp; 15; B 10 mg/kg d1 &amp; 15; O 10 mg/kg d1 &amp; 15. Treatment continued until disease progression or unacceptable toxicity or death; crossover was not permitted. Stratification was by number of metastatic sites (&amp;lt;3, ≥3), number of prior MBC regimens (1 vs 2), and disease-free interval for first-line patients (≤6 months, &amp;gt;6 months). The primary endpoint was PFS; secondary endpoints included OS, objective response rate (ORR), and safety. MET immunohistochemistry (IHC) was performed centrally for exploratory analyses. Results: 185 patients were enrolled from 30 US and 37 EU sites: median age was 53 years (range 30-79); 77% and 23% were treated in the first- and second-line settings, respectively. Baseline characteristics were balanced. Efficacy data for the ITT population are shown in Table 1. The distribution of MET expression using the NSCLC diagnostic algorithm is shown in Table 2. The MET 2+/3+ group was too small for efficacy analyses. Frequently observed AEs (all grades) included peripheral edema (58% vs 59% vs 18%), fatigue (47% vs 41% vs 48%) and diarrhea (53% vs 22% vs 50%), in the P+B+O vs P+O vs P+B arms, respectively. No new safety signals were observed. Table 1Table 1ITT populationP+B+O n = 63P+O n = 60P+B (control) n = 62Median PFS, months7.35.47.2HR vs control (95% CI)1.08 (0.69 - 1.70)1.74 (1.13 - 2.78)-Median OS, months14.713.417.4HR vs control (95% CI)1.35 (0.74 - 2.44)1.88 (1.00 - 3.54)-ORR,% (95% CI)42 (29 - 57)28 (16 - 41)55 (41 - 68) Conclusions: In the ITT population, the addition of O to either P+B or to P alone did not improve PFS and other clinical outcomes compared with P+B alone. Further exploratory subgroup analyses are ongoing. Table 2Table 2MET IHC score01+2+3+Not availablen (%)81 (44)75 (41)21 (11)1 (0.5)7 (4) Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-01.
934-27 Patterns of Target Lesion Calcification in Coronary Artery Disease
Authors: Gary S. Mintz, Jeffrey J. Popma, Augusto D. Pichard, Kenneth M. Kent, Lowell F. Satler, Ya Chien Chuang, Gaston R. Dussaillant, Christine J. Ditrano, Martin B. Leon
Journal: Journal of the American College of Cardiology (1995)
Type II Collagen Gene Variants and Inherited Osteonecrosis of the Femoral Head
Authors: Yu-Fen Liu, Wei-Ming Chen, Yung-Feng Lin, Ruei-Cheng Yang, Ming-Wei Lin, Ling-Hui Li, Ya-Hui Chang, Yuh-Shan Jou, Pei-Yu Lin, Jih-Shyun Su, Shiu-Feng Huang, Kwang-Jen Hsiao, Cathy S.J. Fann, Hun-Way Hwang, Yuan-Tsong Chen, Shih-Feng Tsai
Journal: New England Journal of Medicine (2005)

Avascular necrosis of the femoral head (ANFH) causes disability that often requires surgical intervention. Most cases of ANFH are sporadic, but we identified three families in which there was autosomal dominant inheritance of the disease and mapped the chromosomal position of the gene to 12q13.We carried out haplotype analysis in the families, selected candidate genes from the critical interval for ANFH on 12q13, and sequenced the promoter and exonic regions of the type II collagen gene (COL2A1) from persons with inherited and sporadic forms of ANFH.We identified a G-->A transition in exon 50 of COL2A1 in affected members of a four-generation family with ANFH. This transition predicts the replacement of glycine with serine at codon 1170 in a GXY repeat of type II collagen. Another pedigree was shown to harbor the same transition, but the mutant allele occurred on a different haplotype background. In a third family, a G-->A transition in exon 33 of the gene, causing a glycine-to-serine change at codon 717, was detected. No mutation was found in the COL2A1 coding region in sporadic cases of ANFH.All the patients with familial ANFH whom we studied carried COL2A1 mutations. In families with ANFH, haplotype and sequence analysis of the COL2A1 gene can be used to identify carriers of the mutant allele before the onset of clinical symptoms, allowing the initiation of measures that may delay progression of the disease.
[602] INHIBITION OF HCV REPLICATION BY PSI-6130: CHARACTERIZATION OF ACTIVITY IN THE HCV REPLICON SYSTEM
Authors: W.R. Jiang, S. Ali, S. Le Pogam, C. Daniel, S. Chiu, T. Kretz, I. Najera, P. Furman, N. Cammack, J. Symons
Journal: Journal of Hepatology (2007)
Does Z-Protein Have a Role in Transport of Bilirubin and Bromosulfophthalein by Isolated Perfused Rat Liver?
Authors: Lorenz Theilmann, Yacov R. Stollman, Irwin M. Arias, Allan W. Wolkoff
Journal: Hepatology (1984)

Bilirubin and other organic anions are transported in serum avidly bound to albumin from which they are extracted and transferred into the hepatocyte where they bind to cytosolic proteins. Two abundant organic anion binding proteins, ligandin and Z-protein, were previously purified from liver cytosol and characterized. Other studies in isolated perfused rat liver revealed that selectively increased cytosolic ligandin concentration, following phenobarbital treatment or thyroidectomy, directly correlated with net bilirubin uptake which resulted from reduced bilirubin efflux. To clarify the role of Z-protein in hepatic organic anion transport, we have now determined the kinetics of bilirubin and bromosulfophthalein (BSP) uptake in isolated perfused liver of normal rats and compared results to rats in which Z-protein, but not ligandin, was selectively increased following treatment with clofibrate (ethylchlorophenoxy-isobutyrate). These studies revealed that despite a 147% induction of Z-protein in treated animals, there was no effect on influx or efflux of tracer doses of bilirubin or BSP. Addition of albumin to the protein-free 10% fluorocarbon perfusate reduced influx of 3H-bilirubin (p less than 0.03) and tended to reduce influx of BSP. In this situation, there was still no influence of Z-protein concentration on efflux. These studies indicate that Z-protein does not appear to play a role in the hepatic uptake of bilirubin and BSP.
Riedel's thyroiditis with multiple organ fibrosis.
Authors: D Davies, P Furness
Journal: Thorax (1984)

of Denison and colleagues are not major (see below).Our technique is based on a general evaluation of gas behaviour during the several phases of respiration.'Hence all equa- tions are absolute closed solutions for each phase of breathing.Like the approach of Denison and colleagues, we correct for uneven volume to function by dividing instantaneous absorbable gas concentrations (carbon monoxide, acetylene) by simultaneous inert gas (helium) concentration.Mild to moderate maldistribution does not
92. Efficient Trangene Expression in Central Nervous System through a Non-Integrative Lentiviral Vector
Authors: Stephanie Philippe, Che Serguera, Sebastien Bonnel, Christelle Vetu, Martine Barkats, Caroline Petit, Marc Abitbol, Chamsy Sarkis, Jacques Mallet
Journal: Molecular Therapy (2005)

Lentiviral vectors are widely used in experimental gene transfer and are a promising tool for clinical applications, particularly for the treatment of neurodegenerative diseases. However, one of the most important limits to the application of this technology to humans is the risk of insertional mutagenesis through the integration of the viral genome into the host cell chromatin. This risk remains poorly evaluated and uncontrolled. In order to eliminate this risk, we have developed a lentiviral vector derived from the human immunodeficiency virus type 1 lacking integration property. After cell transduction, the vector genome persists in an extrachromosomic circular form in the nucleus and allows an effective and stable transgene expression in vitro and in vivo.
Phosphoproteomic study of breast cancer: quantitative analysis of SH2 binding proteins.
Authors: K Machida, KP Claffey, CM Thompson, S Hong, D Shin, BJ Mayer
Journal: Cancer Research (2009)

Abstract Abstract #2034 Background: An important biological process involved in breast cancer cell is tyrosine phosphorylation. Particularly, two tyrosine kinases, Src and HER2, are over expressed in invasive breast cancer tissues and both are considered excellent prognostic markers and therapeutic targets. Since tyrosine kinases transduce downstream signals by phosphorylating substrate proteins, leading to cellular responses, we assume the status of tyrosine-phosphorylated proteins in tumors can also provide molecular markers for breast cancer. Recently we established a method termed SH2 profiling, in which a battery of Src Homology 2 (SH2) domains are used to profile proteomes based on interaction between SH2 domains and tyrosine phosphorylated proteins. In this study we developed a semi-automated method to quantify SH2 binding proteins on multiple blots, and explored the feasibility of SH2 binding patterns as potential molecular markers for breast cancer. Material and Methods: Protein lysates from 10 breast cancer patient tissues as well as cancer cell lines were prepared and loaded into multiple precast gels. Proteins were separated using a SDS-PAGE multigel apparatus and transferred onto nitrocellulose membranes. Blocked membranes were incubated with HRP-labeled GST-SH2 domain probes, and SH2 binding patterns were detected by chemiluminescence with a phosphorimager. To correct blot-to-blot variation, we produced a semi-automated imaging tool for multiple blots. SH2 binding proteins were individually quantified based on their molecular sizes on blots, and different breast cancer samples were compared using the SH2 binding profiles. Results and discussion: 1. We have developed a method to quantify and incorporate data from multiple protein blots, a task that is always challenging due to blot-to-blot variation. 2. Using the semi-automated quantitation approach, large numbers of SH2 binding proteins in breast cancer samples were analyzed. SH2 domains including Vav2 and Eat2 bound strongly to proteins even in HER-2 negative tumors suggesting activation of HER-2 independent tyrosine kinase signaling pathways in breast cancer. 3. Further development of the quantitation method is underway to determine if specific SH2 binding patterns are potential prognostic molecular markers for breast cancer. This study is supported by the Connecticut Breast Health Initiative, Inc. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2034.
DOES PARASYMPATHETIC-MEDIATED CHANGE IN RESTITUTION AND ALTERNANS CHARACTERISTICS CONTRIBUTE TO VAGAL ATRIAL FIBRILLATION?
Authors: David Gordon, Rishi Arora, Roger Villuendas, Brandon Benefield, Kathy Harris, Rodney Greene, Greg Shade, Jeffrey J. Goldberger, Alan H. Kadish, Jason Ng
Journal: Journal of the American College of Cardiology (2010)
Narrow-band imaging in the evaluation of villous morphology: a feasibility study assessing a simplified classification and observer agreement
Authors: R. Singh, G. Nind, G. Tucker, N. Nguyen, R. Holloway, J. Bate, M. Shetti, B. George, W. Tam
Journal: Endoscopy (2010)

See also: Commentaire de travail de R. Singh et al., pp. 889Endoscopy 2010; 42(11): 994-995DOI: 10.1055/s-0032-1306706
Implementation of an electronic health record
Authors: J. L. Haughom
Journal: BMJ (2011)

Involves numerous challenges, but examples show it can be done successfully

Implementing an electronic health record along with computerised provider order entry and clinical decision support is hard. Integrating these advanced technologies into a complex and rapidly changing healthcare delivery environment is a major task, but the associated cultural, process, and change management obstacles make the task even harder. Furthermore, the challenges and costs often accrue long before any real value of the effort is seen.

The current controversy regarding the NHS effort to implement a system-wide electronic health record is a good case study of how difficult these initiatives can be.1 When health systems encounter the associated and inevitable difficulties, the natural inclination is to question whether the aggravation and effort is worthwhile. This is clearly at the core of the debate in the United Kingdom regarding the NHS effort. At such times, leaders who are seriously interested in improving the safety, quality, efficacy, and cost of care need to do what all good leaders do—pause, carefully assess the situation, and learn from the experience of their efforts as well as that of others. They should then use this knowledge to determine how to achieve the ultimate goals of the initiative—better …
Interaction of angiotensin II with the angiotensin type 2 receptor inhibits the cardiac transient outward potassium current
Authors: R Caballero
Journal: Cardiovascular Research (2004)

The Ca2+ -independent transient outward K+ current (Ito) plays a crucial role in shaping the cardiac action potential. In the present study, we examined whether angiotensin II (AngII) regulated the Ito as well as the putative intracellular cascade responsible for the effects.Ito was recorded in rat ventricular myocytes using the nystatin-perforated patch-clamp configuration.AngII (0.1 microM) inhibited Ito (21.9+/-4.8% at +40 mV), but not the IK1, in a voltage- and time-independent manner. The inhibition decreased at concentrations higher than 1 microM resulting in a bell-shaped dose-response curve (IC50 = 3.1+/-1.5 microM). The blocking effects were abolished in the presence of the type 2 AngII receptor (AT2R) antagonist PD123319, but not in the presence of the selective type 1 AngII receptor (AT1R) antagonist candesartan. Moreover, the selective AT2R agonist CGP42112A completely reproduced the effects of AngII (20.5+/-2.4% of block at +40 mV), indicating that AngII-induced Ito block was mediated via stimulation of AT2R. Furthermore, selective stimulation of AT2R by CGP42112A significantly prolonged the rat atrial action potentials recorded using conventional microelectrode techniques. The AngII-induced inhibition of I(to) was not modified by either Npi-nitro-L-arginine-methyl ester (L-NAME) or eicosatetrayonic acid (ETYA), indicating that neither the nitric oxide (NO)-guanosine 3',5'-cyclic monophosphate (cGMP) system nor the arachidonic acid cascade was implicated in the effects of AngII on Ito. However, the AngII-induced Ito inhibition was completely abolished by the serine/threonine phosphatase type 2A (PP2A) inhibitors, okadaic acid and cantharidin, but not by the inactive analog of okadaic acid, 1-norokadaone. Intracellular application of PP2A decreased Kv4.2 currents recorded in transiently transfected Chinese hamster ovary cells (CHO).These results indicate that AngII activates PP2A through the stimulation of the AT2R, resulting in a decrease of the Ito amplitude.
Diaphragm thickness and inspiratory strength in patients with Duchenne muscular dystrophy
Authors: P. F. De Bruin, J. Ueki, A. Bush, Y. Khan, A. Watson, N. B. Pride
Journal: Thorax (1997)

There is little information on the morphometric characteristics of the diaphragm in patients with Duchenne muscular dystrophy.The thickness of the diaphragm was measured at the zone of apposition using B mode ultrasonography in 10 boys with Duchenne muscular dystrophy of mean (SD) age 10.3 (1.3) years and 12 normal controls of mean (SD) age 11.3 (2.0) years during relaxation (DiTrelax) and during maximum effort inspiratory manoeuvres (DiTPimax) at functional residual capacity.DiTrelax was greater in the patients with Duchenne muscular dystrophy (1.74 (0.21) mm) than in controls (1.48 (0.20) mm), mean difference (95% CI) 0.26 (0.08 to 0.44), despite considerable impairment of maximum effort inspiratory mouth pressure (Pimax) (patients with Duchenne muscular dystrophy -37 (8) cm H2O, controls -80 (33) cm H2O), mean difference (95% CI) 43 (65 to 20). During a Pimax manoeuvre, compared with measurements taken during relaxation, the diaphragm thickened 1.6 times in patients with Duchenne muscular dystrophy and 2.3 times in controls (DiTPimax 2.62 (0.7) mm and 3.5 (0.85) mm, respectively), mean difference (95% CI) -0.88 (-1.58 to -0.18).Resting diaphragm thickness is increased in young patients with Duchenne muscular dystrophy with impaired respiratory muscle force. This finding could be analogous to the pseudo-hypertrophy that is observed in some limb muscle groups.
HIGH BLOOD SUGAR WITHOUT GLYCOSURIA
Authors: Arthur H. Terry
Journal: JAMA (1927)

To the Editor:  —A correspondent (The Journal, January 8, p. 121) inquires about the significance of high blood sugar without glycosuria. The reply seems conservative if not informative. These cases are not infrequent, and they are more often in the older diabetic patients and the cases associated with nephritis and hypertension. A recent patient of mine had supposed her condition satisfactory from the fact that the urine, which formerly contained sugar, had been sugar free the past two years. Her fasting blood sugar was over 200, and she was confined to bed with so-called rheumatic aches and pains and stiffness for six months. Her carbohydrates were reduced to 100 Gm. but without effect on the blood sugar or the clinical condition. Insulin was then given up to 20 units three times a day until her blood sugar was driven down to 100 fasting. Since then her aches and pains have
Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults
Authors: Seema Jain, Wesley H. Self, Richard G. Wunderink, Sherene Fakhran, Robert Balk, Anna M. Bramley, Carrie Reed, Carlos G. Grijalva, Evan J. Anderson, D. Mark Courtney, James D. Chappell, Chao Qi, Eric M. Hart, Frank Carroll, Christopher Trabue, Helen K. Donnelly, Derek J. Williams, Yuwei Zhu, Sandra R. Arnold, Krow Ampofo, Grant W. Waterer, Min Levine, Stephen Lindstrom, Jonas M. Winchell, Jacqueline M. Katz, Dean Erdman, Eileen Schneider, Lauri A. Hicks, Jonathan A. McCullers, Andrew T. Pavia, Kathryn M. Edwards, Lyn Finelli
Journal: New England Journal of Medicine (2015)

Community-acquired pneumonia is a leading infectious cause of hospitalization and death among U.S. adults. Incidence estimates of pneumonia confirmed radiographically and with the use of current laboratory diagnostic tests are needed.
Diagnostic Cytology and Its Histopathologic Bases
Authors: Tilde S. Kline
Journal: JAMA (1969)

After almost a year's absence from the book stores, Koss's<i>Diagnostic Cytology</i>is back again in its second edition. This is probably the most complete book on cytology available, correlating the exfoliated cell with its parent healthy or diseased organ. As is the trend of modern texts, the new book is almost 300 pages longer than the original. Among its new features are a greatly expanded discussion of basic cellular structures with abundant photographs of electron microscopy. There also are several new chapters by Miles on the chromosome. Coverage of normal female genital-tract cytology has been increased by more illustrations of excellent quality. However, the second edition still describes what are probably metaplastic cells as parabasal cells with intercellular bridges. Another error has been corrected. In the new volume a special variety of multinucleated cells which previously had been called "trophoblastic syncitial cells" now is correctly identified as a cell
An Introduction to the Principles of Disease
Authors: Frances K. Widmann
Journal: JAMA (1977)

Old traditions die hard. Walter's "Introduction to the Principles of Disease" exemplifies the notion that a detailed, all-inclusive pathology course is indispensable in training students for a career in health care. Since his audience is the allied health worker, he has simplified concepts and exposition and adopted the educationalists' shibboliths of outlines, behavorial objectives, and review questions, but this is still the second-year course in pathology of the old medical curriculum. For allied health curriculums able to give a semester-long pathology course, this book fills the void left when the more elementary of Boyd's textbooks went out of business. The prose style is pedestrian, with many prepositions and passive constructions, but the material is clear, complete, and well organized. In addition to the fundamental mechanisms of general pathology and a quick canvass of temperature regulation, fluid balance, nutritional-metabolic interactions, and the etiologic categories of infection, there is a procession of
STUDIES ON THE CHEMOTHERAPY OF THE HUMAN MALARIAS. IX. EFFECT OF PAMAQUINE ON THE BLOOD CELLS OF MAN 123
Authors: David P. Earle, Frederick S. Bigelow, Charles G. Zubrod, Charles A. Kane
Journal: Journal of Clinical Investigation (1948)

Pamaquine (6-methoxy-8-amino [N-diethylaminoisopentyl] quinoline) is recognized to be a potentially dangerous drug.However, a definitive appraisal of its hazard had not been achieved at a time when the further exploration of the antima- larial activity of the 8-aminoquinolines was con- sidered advisable.Pamaquine toxicity can in- volve the gastro-intestinal tract, the central nerv- ous system, and the circulating blood.Symptoms referable to the gastro-intestinal tract and the cen- tral nervous system may be annoying, but there is no evidence that they constitute a hazard to life or persist beyond the termination of therapy.Effects on the blood do constitute a serious hazard and are considered in this paper. MATERIALS AND METHODSMost of the patients utilized as subjects either were having malaria at the time of the observations or had had the disease from one to six weeks previously.None of the patients had malaria long enough to be considered likely subjects for the development of blackwater fever.Most subjects were suffering from asymptomatic neuro- syphilis and many had received prior antiluetic therapy.1 The work described in this paper was done under a contract, recommended by
Salivary Secretion of Blood-Group Factors in Cancer
Authors: Melvin J. Krant
Journal: JAMA (1968)

Several recent papers have indicated that a relationship exists between the clinical course of cancer and the blood-group substance secretor factor in saliva.<sup>1,2</sup>An etiologic relation in 88 cases of primary bronchogenic carcinoma in the Salt Lake City area described a distinct lack of nonsecretors.<sup>3</sup>To confirm this finding, an analysis was conducted of the frequency of this particular genetic factor occurring in a series of patients with various cancers at the Lemuel Shattuck Hospital. <h3>Methods</h3> In 1966, studies were made on 195 patients with cancer who admitted to the Lemuel Shattuck Hospital. Blood-group analysis and salivary-secretor status were obtained; an analysis of the clinical course of the patient was made. Five milliliters of saliva was collected; standard techniques were used for treatment of saliva and for testing it with an extract of<i>Ulex europaeus</i>.<sup>4</sup> All nonsecretor saliva was retested with the extract and with 0 cells.