tbuckley/cabot-search huggingface dataset:
771 DECLINE OF DETECTABLE RESISTANCE MUTATIONS WITHIN THE HCV NS3 PROTEASE QUASISPECIES DURING LONG-TERM FOLLOW-UP AFTER TREATMENT WITH TELAPREVIR
Authors: S. Susser, N. Forestier, J. Vermehren, N. Grigorian, U. Karey, S. Zeuzem, C. Sarrazin
Journal: Journal of Hepatology (2010)
765 RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND, DOSE RESPONSE (RPCDBDR) TRIAL OF CTS-1027, AN INHIBITOR OF MATRIX METALLOPROTEASES (MMPS) IN PATIENTS WITH HCV WHO HAD FAILED PRIOR THERAPIES
Authors: P.J. Pockros, S.C. Gordon, A. McCullough, M. Charlton, N. Bzowej, J. Vierling, M. Bansal, B. Yoffe, G. Everson, M. Huyghe, A. Fox, S. Mento, O. Bohm, B. Plouffe, R. Cross, M. Shiffman
Journal: Journal of Hepatology (2010)
Judith Ann Stewart (nee Emmerson)
Authors: N. Direkze
Journal: BMJ (2002)

Specialist registrar in neurology Atkinson Morley's Hospital, London (b 1963; q Oxford/St Thomas's Hospital, London, 1987), died from breast cancer on 28 January 2002. 

Judy worked in Oxford and Bristol before choosing her specialty—neurology. Her research at St Thomas's resulted in what is now the largest and longest running stroke registry in Europe. She was diagnosed with breast cancer in October 1997. She returned to work but required more treatment for recurrence in 1999. Despite this she continued to make efforts to return to work. She leaves a husband, Jim.
320. Antitumor Effect of Intrahepatic Interleukin-12 Expression from a Regulable Plasmid Vector in Murine Models of Primary and Metastatic Liver Cancer
Authors: Maider Zabala, Ruben Hernandez-Alcoceba, Margarita Ecay, Ignacio Melero, Christine Perret, Ivan Penuelas, Jesus Prieto, Gabriela M. Kramer
Journal: Molecular Therapy (2005)

Interleukin-12 (IL-12) is a potent antitumoral cytokine, but it can be toxic at high doses. In order to minimize side effects, we have optimized the Tet-on inducible system for liver-specific expression of murine IL-12 with reduced basal activity. The plasmid was transferred to mice by the hydrodynamics-based procedure and the antitumor effect of IL-12 was evaluated using two different animal models.
Neuronal MHC-I display in T-cell mediated neurodegeneration
Authors: Carolina Cebrián, Fabio Zucca, Luigi Zecca, John Loike, David Sulzer
Journal: Molecular Neurodegeneration (2013)

Parkinson’s disease (PD) and other disorders feature the degeneration of ventral midbrain (VM) catecholamine neurons. Recent data suggest that neuroinflammatory mechanisms contribute to a cascade of events leading to chronic neuronal degeneration.

In primary murine neuronal cultures, substantia nigra (SN) and locus coeruleus (LC) neurons are induced to express the major histocompatibility class I complex (MHC-I) by the proinflammatory cytokine, γ-interferon, L-DOPA, or conditioned medium from microglia exposed to α-synuclein or NM. SN DA neurons, moreover, process the foreign protein ovalbumin to an antigenic peptide that is presented by their MHC-I and triggers their specific destruction by CD8+ killer T-cells. In human postmortem samples, we find by immunolabel, mRNA profiling, and proteomic analysis that neuromelanin (NM)-containing catecholamine SN and LC neurons in adult human control and PD brains express MHC-I, often in proximity to CD8+ T-cells. These data reveal a novel inflammatory T-cell mediated neurodegenerative processes that could underlie neuronal death.
THE LONG-TERM COMPARATIVE RESULTS OF THREE DIFFERENT LOBOTOMY PROCEDURES
Authors: NORMAN L. PAUL, EDWARD FITZGERALD, MILTON GREENBLATT
Journal: American Journal of Psychiatry (1957)

A 5-year follow-up of 116 chronic mentally ill patients, divided into 3 groups each of which was subjected to a different lobotomy procedure (e.g., full bilateral, bimedial, and unilateral operations) disclosed that bimedial lobotomy was superior to either of the other 2 procedures in the treatment of chronic mentally ill patients. "Significant" improvement at 5 years was found in 21 or 65% of the bimedial group, compared with lesser frequencies in the other 2 groups. Also, at 5 years, there was an improvement in work adjustment over that observed at 1 year which was most evident in the bimedial group. The greater relief of anxiety, tension, hostility, and disorganization at 5 years after bimedial operation emphasizes its therapeutic superiority. The number of cases who had one or more convulsive seizures was greater at 5 years than at 1 year. However, only 1 person had status epilepticus and this proved to be fatal.
Ageism occurs in prevention of heart disease too
Authors: T. Marshall
Journal: BMJ (2000)

EDITOR—Bowling's article on ageism in cardiology focused exclusively on the treatment of ischaemic heart disease.1 She might also have looked at prevention.

I have constructed a model of prevention of cardiovascular disease. Broadly speaking, lowering blood pressure by 10 mm Hg systolic (or cholesterol concentration by 20%) reduces the risk of an ischaemic heart disease event by about 30%. This is roughly the effect of an antihypertensive drug or a statin. As the reduction in risk depends on the initial level of …
Will Evidence Be Enough to Promote Interactive Communication for the Benefit of Patients?
Authors: Alain Braillon
Journal: Annals of Internal Medicine (2010)

Letters20 July 2010Will Evidence Be Enough to Promote Interactive Communication for the Benefit of Patients?Alain Braillon, MD, PhD, Aurore Bernardy-Prud'homme, MD, and Gerard Dubois, MD, PhDAlain Braillon, MD, PhDFrom Public Health, Northern Hospital, 80000 Amiens, France.Search for more papers by this author, Aurore Bernardy-Prud'homme, MDFrom Public Health, Northern Hospital, 80000 Amiens, France.Search for more papers by this author, and Gerard Dubois, MD, PhDFrom Public Health, Northern Hospital, 80000 Amiens, France.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-2-201007200-00012 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Foy and colleagues (1) provided evidence to support common sense, showing that patients with depression or diabetes have better outcomes when family physicians and specialists work together as a team, with different kinds of collaboration (for example, e-mail or face-to-face conversations).We recently conducted a study to improve quality of care, specifically evaluating the follow-up after discharge in a series of 176 persons aged 15 to 25 years who attempted suicide (mean age, 20 years) and were hospitalized (mean duration, 1.1 day) in the 9 main hospitals in Picardie, France. Among the 90% of persons who were ...Reference1. Foy R, Hempel S, Rubenstein L, Suttorp M, Seelig M, Shanman R, et al. Meta-analysis: effect of interactive communication between collaborating primary care physicians and specialists. Ann Intern Med. 2010;152:247-58. [PMID: 20157139] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Alain Braillon, MD, PhD; Aurore Bernardy-Prud'homme, MD; Gerard Dubois, MD, PhDAffiliations: From Public Health, Northern Hospital, 80000 Amiens, France.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMeta-analysis: Effect of Interactive Communication Between Collaborating Primary Care Physicians and Specialists Robbie Foy , Susanne Hempel , Lisa Rubenstein , Marika Suttorp , Michelle Seelig , Roberta Shanman , and Paul G. Shekelle Will Evidence Be Enough to Promote Interactive Communication for the Benefit of Patients? Robbie Foy Metrics 20 July 2010Volume 153, Issue 2Page: 131KeywordsAdolescentsConflicts of interestDiagnosis related groupsEvidence based medicineHealth care qualityHospitalizationsPatientsSuicide ePublished: 20 July 2010 Issue Published: 20 July 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Unrecognizable Intramucosal Spread of Diffuse-Type Mucosal Gastric Carcinomas of Less than 20 mm in Size
Authors: None Ninomiya, None Yanagisawa, None Kato, None Tomimatsu
Journal: Endoscopy (2000)

Diffuse-type intramucosal gastric carcinomas sometimes spread within the mucosa beyond their macroscopic margins, often causing positive resection margins upon local resections such as endoscopic mucosal resection.A consecutive series of 34 patients with solitary, small (less than 20 mm in diameter macroscopically), and macroscopically well demarcated diffuse-type mucosal carcinomas, who were treated with gastrectomy followed by detailed pathological examination, were included in the present study. Unrecognizable intramucosal spread is defined as an area of cancer which is indistinguishable macroscopically from its peripheral noncancerous area, and covered by normal epithelium with neither morphologic nor color changes. We examined the extent of unrecognizable intramucosal spread, measuring the maximum distances between macroscopic and microscopic margins on the sections, and investigated its relationship with four factors: location of the lesion, macroscopic size, histologic ulcer formation, and degree of atrophy of the background mucosa.The maximum distance between macroscopic and microscopic margins was significantly larger (maximum 10 mm) in the background mucosas with marked atrophy than in those with little or no atrophy. No other factors, including location, macroscopic size and ulcer formation, correlated with it.We should pay particular attention to unrecognizable intramucosal spread, especially in markedly atrophied mucosa, when treating small diffuse-type mucosal gastric cancer by local resections such as endoscopic mucosal resection. In addition, because of unrecognizable intramucosal spread, a surgical incision margin of at least 10 mm from the macroscopic margin is indicated.
pH‐Controlled Delivery of Nanoparticles into Tumor Cells
Authors: Liang Han, Haojun Ma, Yubo Guo, Yuyang Kuang, Xi He, Chen Jiang
Journal: Advanced Healthcare Materials (2013)

Nanoparticles target tumor cells by pH-controlled means. Nanoparticles carry three synergistic delivery functions: 1) tumor tissue targeting by the EPR effect; 2) tumor cell targeting by pHLIP-mediated membrane-localization; and 3) tumor cell uptake by adsorptive-mediated endocytosis. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Staging laparotomy and splenectomy: Treatment and complications of hodgkin's disease in children
Authors: P. Lanzkowsky, A. Shende, G. Karayalcin, I. Aral
Journal: American Journal of Hematology (1976)

Twenty-five cases of hodgkin's Disease (15 males and 10 females) aged 5 to 17 years were studied from April 1970 to July 1976 (75 month period). Histology revealed that 2 had lymphocytic predominance, 12 had nodular sclerosis, and 11 had mixed cellularity. Pathologic staging revealed that 3 were IA, 1 IB, 5 IIA, 4IIB, 6IIIA, and 6 IIIB. Laparotomy altered the staging in 12 patients (9 were staging up and 3 down). All but 2 patients received extended field radiation, and 5 had recurrence of disease and were treated with combination chemotherapy. Twenty-three are alive without evidence of disease (21-75 months), and the 2 deaths were not due to Hodgkin's Disease but to hemobilia (postliver biopsy) and penumococcal septicemia, purpura fulminans, and disseminated intravascular coagulation (14 months postsplenectomy). Other complications included 2 patients with intestinal obstruction, 1 with postoperative subphrenic abscess, and 1 with streptococcal septicemia and polyarthritis. Nineteen patients received continuous penicillin prophylaxis postoperatively and the 2 with serious infections were amongst the 6 who had not received penicillin or whose penicillin had been discontinued at the time of infection. It is concluded that laparotomy and splenectomy in children is essential for accurate staging but carries significant risk, and continuous penicillin prophylaxis is recommended.
The effect of lung biopsy on lung function in diffuse lung disease
Authors: Z. Daniil, F.C. Gilchrist, S.J. Marciniak, P. Pantelidis, P. Goldstraw, U. Pastorino, R.M. du Bois
Journal: European Respiratory Journal (2000)

The aim of this study was to investigate the effect on lung function of lung biopsy used in the diagnosis of diffuse lung disease carried out by an open procedure or by video-assisted thoracoscopy. One hundred and sixteen patients with diffuse lung disease who attended the Royal Brompton Hospital were studied retrospectively. Thirty five patients underwent open lung biopsy, and 33 video-assisted thoracoscopic biopsy and 48 had their diagnosis made without biopsy. All patients underwent lung function tests before and after surgery, or at an interval of 3-6 months in those who did not undergo biopsy. No significant differences were found in changes in lung function between those who had and had not undergone biopsy, and the proportions of patients whose lung function improved or deteriorated were similar. Lung biopsy by an open procedure or by video-assisted thoracoscopy did not differ in its effects on lung function. The results for older patients, those with severe disease and those with fibrosing alveolitis were the same as for the whole group. Open lung biopsy for the diagnosis of diffuse lung disease does not deleteriously affect lung function whether carried out by an open or a minimally invasive procedure.
Lymphadenopathy associated with monoamine oxidase inhibitors
Authors: Andre M. Kallab, Eileen M. Marley, Debra Frei-Lahr
Journal: American Journal of Hematology (1999)

Fulminant Brain Lymphoid Infiltration in a Patient With Chronic Lymphocytic LeukemiaTo the Editor: Symptomatic involvement of the central nervous system (CNS) in chronic lymphocytic leukemia (CLL) is very rare.We present a TABLE I. Drugs Associated With Lymphadenopathy* Phenytoin Carbamazepine Para-amino salicylic
ET-30 * A PHASE I TRIAL OF AZD7451, A TROPOMYOSIN-RECEPTOR KINASE (TRK) INHIBITOR, FOR ADULTS WITH RECURRENT GLIOBLASTOMA MULTIFORME (GBM)
Authors: T. N. Kreisl, C. Peer, J. Brown, W. D. Figg, H. A. Fine
Journal: Neuro-Oncology (2014)

BACKGROUND: We have shown that inhibition of TrkA both genetically and pharmacologically results in profound inhibition of glioma stem cell migration in vitro and in vivo. AZD7451 is the first in class of highly potent and selective Trk inhibitors and therefore may have significant anti-glioma cell invasive properties. METHODS: We conducted an open label phase I study of AZD 7451 mesylate, with a standard 3 + 3 dose escalation scheme, to determine the MTD and describe pharmacokinetics. The drug was administered as an oral solution (10 mg/ml) at 12 mg, 24 mg, 40 mg, and 60 mg daily. DL3 and DL4 were administered with divided twice daily dosing. Plasma concentrations of AZD7451 were measured with ultra-performance liquid chromatography and tandem mass spectrometry using samples obtained at baseline and various points through the first 4 week cycle of therapy. RESULTS: 14 patients were enrolled. There were no radiographic responses to therapy, and no patients achieved disease control beyond cycle 2. There were no DLTs. Unexpected treatment related toxicities included grade 1-2 thrombocytopenia and anemia. No neurological adverse events related to therapy were observed. All patients were evaluable for C1D1 pharmacokinetics. The majority of samples were below the limit of quantitation (LLOQ) of 0.5 ng/mL by ∼ 4 h post-dose. AZD7451 T1/2 ranged from 20-50 min with once daily or BID dosing. No statistically significant increases in CMAX, AUCINF, T1/2, or volume of distribution were observed as dose increased. CONCLUSIONS: Based on the interim PK analysis for AZD7451 indicating poor oral bioavailability, short <60 min plasma T1/2 half-life, and rapid clearance kinetics, PK exposures are insufficient in humans to inhibit Trk at target plasma concentrations necessary for efficacy in preclinical models. The absence of DLT's or early efficacy signals in GBM patients is also consistent with poor AZD7451 exposures in humans.
Valentine's Day Abstract
Authors: Brenda Butka
Journal: Annals of Internal Medicine (2013)

Ad Libitum5 February 2013Valentine's Day AbstractBrenda Butka, MDBrenda Butka, MDFrom Nashville, Tennessee.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-158-3-201302050-00015 Audio Reading - “Valentine's Day Abstract” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Valentine's Day Abstract," by B. Butka. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Stopthis multicenter trial,controlled and randomized.It's time.I've been double-blindlong enough.We've crunched the numbers—end point: cardiac events—stuttering hearts hopingto disprove the null hypothesiswhich claims no difference.(Edit: hope is not partof peer review, and must go.Delete.)But still, unblinded,the data tend to showa positive risk–benefit ratio,survival advantage approachingstatistical significance.We now knowyou suit me to a p-value of less than point-oh-five.Baby, you're the remedy,a significant savings perQuality-Adjusted Life-Year,the curefor this cracked and unlovely heart.Or at least the currentstandard of care.All I need is yourinformed consentandyouapplied in all directionsforeverrandomly anduncontrolled.Brenda Butka, MDNashville, Tennessee Author, Article, and Disclosure InformationAffiliations: From Nashville, Tennessee.Current Author Address: Brenda Butka, MD; e-mail, [email protected]. PreviousarticleNextarticle Advertisement Audio Reading - “Valentine's Day Abstract” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Valentine's Day Abstract," by B. Butka. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 5 February 2013Volume 158, Issue 3Page: 216KeywordsHeartPeer reviewQuality adjusted life yearsStatistical data ePublished: 5 February 2013 Issue Published: 5 February 2013 Copyright & PermissionsCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Evolutionary Rate Variation in Anthocyanin Pathway Genes
Authors: Y. Lu
Journal: Molecular Biology and Evolution (2003)

Over a broad taxonomic range that spans monocots and dicots, upstream enzymes of the anthocyanin pigment pathway have evolved less rapidly than downstream enzymes. In this article we show that this pattern is also evident within the genus Ipomoea. Specifically, the most upstream enzyme, chalcone synthase (CHS-D), evolves more slowly than the two most downstream enzymes, ancyocyanidin synthase (ANS) and UDP glucose flavonoid 3-oxy-glucosyltransferase (UFGT). This pattern appears not to be due to variation in mutation rates, because the CHS-D gene exhibits higher synonymous substitution rates than the genes for the other two enzymes. Codon-based tests for positive selection suggest that it has been negligible or absent in all three genes. In addition, the mean number of indel-creating events is four times as high in the downstream genes as in CHS-D. Unlike the downstream genes, CHS-D also exhibits evidence of codon bias. Together, the evidence suggests that the difference in nonsynonymous substitution rates between upstream and downstream genes is due to relaxed constraint on the downstream genes rather than a greater frequency of positively selected substitutions.
Modified APC-resistance test: Variable ratios with respect to source of factor V-deficient plasma
Authors: Chung-hsin Ts'ao, Demetra Neofotistos, Maria Oropeza, Shahla Vahabinejad, William G. Finn
Journal: American Journal of Hematology (1997)

A single point mutation of the factor V (FV) gene, leading to the substitution Arg506GIn in the FV molecule (FV-Leiden) and hence resistance to its breakdown by activated protein C (APC), is the most prevalent risk factor for venous thrombosis in the Caucasians. A ratio determined by activated partial thromboplastin time (APTT) of test plasma in the presence or absence of exogenous APC (the APC ratio), is the method widely used to screen individuals with this risk factor for thrombosis. Because of functional defects of vitamin K-dependent clotting factors in patients on oral anticoagulant therapy, this method cannot be applied to those patients without modification. One modification is to mix test plasma (1:5 or 1:10) with FV-deficient plasma so that 80–90% of functioning vitamin K-dependent factors are supplied by the FV-deficient plasma. Even with 10–20% of FV in the mixture, APC-resistance still can be demonstrated. In this report, we present our results of the modified APC-sensitivity assay using FV-deficient plasma from different commercial sources. APC ratios determined by the original method in which test plasma is not mixed with FV-deficient plasma can be significantly different from those determined by the modified method in which test plasma is diluted 1:5 with FV-deficient plasma. This difference between methods was observed not only in normal individuals, but also in FV-Leiden positive individuals, and in patients on warfarin therapy. Further, APC ratios varied significantly depending on the commercial source of the FV-deficient plasma. The modified method is apparently suitable to identity APC-resistance in patients on warfarin therapy, as well as in individuals not receiving anticoagulant treatment. However, one must be aware that APC-resistance ratios obtained with the modified method are likely to be different from those established with the original method, and the source of FV-deficient plasma can be a factor influencing the ratios in the former cases. Am. J. Hematol. 54:214–218, 1997 © Wiley-Liss, Inc.
Rilonacept (IL-1 Trap) Demonstrates Rapid Reduction Of Clinical Symptoms In Patients With Cryopyrin-Associated Periodic Syndromes (CAPS) In A Placebo-Controlled Trial
Authors: R. Cartwright, M. Throne, D. Nadler, M. Mahony, S.P. Weinstein, S.J. Mellis
Journal: Journal of Allergy and Clinical Immunology (2009)
THE USE OF COTTON DENTAL ROLLS FOR EAR DRAINS
Authors: Mearle C Fox
Journal: JAMA (1926)

There is a difference of opinion as to whether irrigation or dry drainage is the more beneficial for acute suppuration of the middle ear, the two being equally well supported by good authority. For the benefit of those who wish to use dry drainage, I would call attention to the use of no. 1, inch and a half, cotton dental rolls, such as are used by dentists for blocking off the secretion from their fields of operation. The roll is cut diagonally across as represented in the illustration, a small portion being left at each end to prevent the cotton from flattening out when being placed in the ear. The ear is first thoroughly cleansed by the use of cotton-tipped applicators and, if need be, by the aid of hydrogen peroxide, followed by drying and whatever antiseptic the clinician prefers. The ear is grasped firmly and