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showing 10 items of 2898 documents

Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Canc…

2018

AbstractPurpose: This single-arm, open-label phase II study evaluated the safety and efficacy of taselisib (GDC-0032) plus fulvestrant in postmenopausal women with locally advanced or metastatic HER2-negative, hormone receptor (HR)-positive breast cancer.Patients and Methods: Patients received 6-mg oral taselisib capsules daily plus intramuscular fulvestrant (500 mg) until disease progression or unacceptable toxicity. Tumor tissue (if available) was centrally evaluated for PIK3CA mutations. Adverse events (AE) were recorded using NCI-CTCAE v4.0. Tumor response was investigator-determined using RECIST v1.1.Results: Median treatment duration was 4.6 (range: 0.9–40.5) months. All patients expe…

Adult0301 basic medicineOncologyCancer Researchmedicine.medical_specialtyDrug-Related Side Effects and Adverse ReactionsClass I Phosphatidylinositol 3-KinasesReceptor ErbB-2Phases of clinical researchBreast NeoplasmsDisease-Free SurvivalArticle03 medical and health sciences0302 clinical medicineBreast cancerInternal medicineAntineoplastic Combined Chemotherapy ProtocolsmedicineHumansAdverse effectFulvestrantAgedAged 80 and overResponse rate (survey)Fulvestrantbusiness.industryImidazolesCancerMiddle Agedmedicine.diseaseOxazepines030104 developmental biologyReceptors EstrogenOncologyHormone receptor030220 oncology & carcinogenesisMutationToxicityFemalebusinessmedicine.drugClinical Cancer Research
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Flexible switching of feedback control mechanisms allows for learning of different task dynamics.

2013

To produce skilled movements, the brain flexibly adapts to different task requirements and movement contexts. Two core abilities underlie this flexibility. First, depending on the task, the motor system must rapidly switch the way it produces motor commands and how it corrects movements online, i.e. it switches between different (feedback) control policies. Second, it must also adapt to environmental changes for different tasks separately. Here we show these two abilities are related. In a bimanual movement task, we show that participants can switch on a movement-by-movement basis between two feedback control policies, depending only on a static visual cue. When this cue indicates that the …

AdultAnatomy and PhysiologyCognitive NeuroscienceMovementFeedback controlNeurophysiologylcsh:MedicineMotor ActivitySocial and Behavioral SciencesNeurological SystemFeedbackMotor ReactionsYoung Adult03 medical and health sciencesLearning and Memory0302 clinical medicineHuman–computer interactionTask Performance and AnalysisMotor systemReaction TimePsychologyLearningHumansMotor activitylcsh:ScienceBiologySensory cue030304 developmental biologyMotor SystemsComputational NeurosciencePhysics0303 health sciencesMultidisciplinarybusiness.industrylcsh:RCognitive PsychologyMotor commandsRoboticsMental HealthArmMedicinelcsh:QArtificial intelligenceCuesbusiness030217 neurology & neurosurgeryHuman learningResearch ArticleNeurosciencePLoS ONE
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Synthetic antioxidants: biochemical actions and interference with radiation, toxic compounds, chemical mutagens and chemical carcinogens.

1984

Abstract Biological actions of 4 commonly used synthetic antioxidants — butylated hydroxyanisole, butylated hydroxytoluene, ethoxquin and propul gallate — on the molecular, cellular and organ level are compiled. Such actions may be divided into modulation of growth, macromolecule synthesis and differentiation, modulation of immune response, interference with oxygen activation and miscellaneous. Moreover, an overview of beneficial and adverse interactions of these antioxidants with exogenous noxae is given. Beneficial interactions include radioprotection, protection against acute toxicity of chemicals, antimutagenic activity and antitumorigenic action. Possible mechanisms of the antitumorige…

AdultAntioxidantmedicine.medical_treatmentButylated HydroxyanisoleMutagenAnisolesIn Vitro TechniquesToxicologymedicine.disease_causeKidneyRadiation ToleranceAntioxidantschemistry.chemical_compoundMiceEthoxyquinGallic AcidNeoplasmsmedicineButylated hydroxytolueneAnimalsHumansDrug InteractionsPropyl GallateCarcinogenCarcinogen MetabolismKidney metabolismBiological activityButylated HydroxytolueneRatsBiochemistrychemistryLiverEnzyme InductionAntibody FormationCarcinogensQuinolinesButylated hydroxyanisoleMutagensToxicology
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Treatment outcome of invasive mould disease after sequential exposure to azoles and liposomal amphotericin B

2009

Objectives To analyse the potential antagonism between azoles, which inhibit ergosterol synthesis, and polyenes, which bind directly to ergosterol in cell membranes, in patients receiving sequential azole-polyene treatment. Methods In an earlier randomized, double blind study of liposomal amphotericin as initial therapy for invasive filamentous fungal infection (IFFI), a 3 mg/kg/day dose had a favourable overall response rate of 50% and 12 week survival rate of 72%. No improved outcome was seen with 10 mg/kg/day for the first 14 days. The study population was further analysed for the effect of prior azole exposure on treatment responses to liposomal amphotericin B. The protocol allowed prio…

AdultAzolesMaleMicrobiology (medical)medicine.medical_specialtyAntifungal AgentsAdolescentmedicine.drug_classAntibioticsPharmacologyAspergillosisGastroenterologyYoung AdultPharmacotherapyDouble-Blind MethodAmphotericin BInternal medicineAmphotericin BmedicineHumansDrug InteractionsPharmacology (medical)ChildSurvival rateMycosisAgedPharmacologyVoriconazolechemistry.chemical_classificationbusiness.industryInfantMiddle Agedmedicine.diseaseTreatment OutcomeInfectious DiseasesMycoseschemistryChild PreschoolAzoleFemalebusinessmedicine.drugJournal of Antimicrobial Chemotherapy
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False positive rate of an arrayCGH platform for single-cell preimplantation genetic screening and subsequent clinical application on day-3

2013

In this work, false positive rate of an arrayCGH platform for its use in day-3 single-blastomere analysis was calculated. For this purpose, 38 embryos diagnosed as abnormal on day-3 by FISH were re-biopsied on day-4. Single-cell day-4 arrayCGH diagnosis was then performed. A successful amplification was obtained in 97.4 % (37/38) of the day-4 cells analysed by arrayCGH. Day-3 FISH and day-4 arrayCGH diagnosis were concordant in 35/37 cases. The two discordant embryos were spread and all the cells from each embryo were re-analysed by FISH on day 5. The same error rate (2.7 %) for day-3 FISH and day-4 arrayCGH was obtained when comparing day-5 FISH re-analysis. After this pre-clinical phase, …

AdultBlastomeresmedicine.medical_specialtyTime FactorsPregnancy RateBiopsyConcordanceClinical pregnancyBiologySensitivity and SpecificityMiscarriagePregnancyarrayCGHDay-5 FISH re-analysisGeneticsmedicineChromosomes HumanHumansFalse Positive ReactionsEmbryo ImplantationGenetic TestingProspective StudiesIn Situ Hybridization FluorescenceGenetics (clinical)CryopreservationGynecologyComparative Genomic HybridizationReproducibility of ResultsObstetrics and GynecologyGeneral MedicineAneuploidyEmbryo Transfermedicine.diseaseBlastocystReproductive MedicineBlastomere biopsyBlastomere biopsyFish <Actinopterygii>Day-3 PGSFemaleFalse positive rateDevelopmental Biology
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Inhibition of dextromethorphan metabolism by moclobemide.

1998

This pilot study was conducted to evaluate the potential of the new antidepressant moclobemide to inhibit the cytochrome enzyme P4502D6 (CYP2D6) using the cough suppressant dextromethorphan as a substrate in four extensive metabolizers (EM) of debrisoquine. The subjects received seven oral doses of 20 mg dextromethorphan at 4-h intervals over 2 days (1 and 2) and subsequently moclobemide (300 mg b.i.d.) for 9 days. On days 10 and 11, they received seven doses of 20 mg dextromethorphan in addition to moclobemide. During monotreatment and combined treatment, blood was collected on days 2 and 11, respectively, for determination of dextromethorphan and its demethylated metabolites using automat…

AdultCYP2D6animal structuresMonoamine Oxidase InhibitorsAdolescentMoclobemidePharmacologyDextromethorphanchemistry.chemical_compoundPharmacokineticsOral administrationDextrorphanMoclobemideMedicineHumansDrug InteractionsBiotransformationPharmacologybusiness.industryDextromethorphanDrug interactionAntidepressive AgentsDebrisoquinechemistryArea Under CurveBenzamidesbusinessmedicine.drugPsychopharmacology
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Soluble-protein and antigenic heterogeneity in axenic Blastocystis hominis isolates: pathogenic implications.

1999

The protein profile and the antigenic cross-reactivity of 18 axenic isolates of Blastocystis hominis obtained from symptomatic patients with chronic diarrhea (14 isolates) showing no evidence of parasitic etiology and from patients with acute diarrhea attributable in 2 cases to Salmonella spp. were analyzed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of soluble proteins showed the existence of a common profile composed of 31 bands, with molecular weights ranging between 24 and >200 kDa, and minor differences in the proteins of 149, 118, 106, 50, 48, 47, and 30 kDa. These differences allowed us to classify the strains into three related patterns (I–III). In an indirect immunof…

AdultDiarrheaSalmonellaImmunodiffusionProtozoan ProteinsAntigens ProtozoanHIV InfectionsBlastocystis InfectionsBiologyLoboseaCross Reactionsmedicine.disease_causeMicrobiologyAntigenmedicineAnimalsHumansBlastocystis hominisAxenicGel electrophoresisBlastocystisGeneral VeterinaryGeneral Medicinebiology.organism_classificationVirologyMolecular WeightDiarrheaInfectious DiseasesInsect ScienceAcute DiseaseChronic DiseaseSalmonella InfectionsProtozoaParasitologyElectrophoresis Polyacrylamide Gelmedicine.symptomParasitology research
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Medication safety in a psychiatric hospital

2007

Objective: We sought to assess the epidemiology of medication errors (MEs) and adverse drug events (ADEs) in a psychiatric hospital. Methods: We conducted a 6-month prospective observational study in a 172-bed academic psychiatric hospital. Errors and ADEs were found by way of chart review, staff reports and pharmacy intervention reports. Physicians rated incidents as to the presence of injury, preventability and severity of an injury. Serious MEs were nonintercepted MEs with potential for harm (near misses) and preventable ADEs. Results: We studied 1871 admissions with 19,180 patient-days. The rate of ADEs and serious MEs were 10 and 6.3 per 1000 patient-days, respectively. Preventable ADE…

AdultHospitals PsychiatricMalePediatricsmedicine.medical_specialtyanimal structuresDrug-Related Side Effects and Adverse Reactionsbusiness.industryPublic healthPsychological interventionPharmacyLength of StayPsychiatry and Mental healthPatient safetyPharmacotherapyEpidemiologyEmergency medicinemedicineHumansMedication ErrorsPsychiatric hospitalFemaleObservational studyProspective StudiesbusinessGeneral Hospital Psychiatry
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Negative biopsy of focal hepatic lesions: Decision tree model for patient management

2019

OBJECTIVE. The purpose of this study was to investigate patient- and procedure-related variables affecting the false-negative rate of ultrasound (US)-guided liver biopsy and to develop a standardized patient-tailored predictive model for the management of negative biopsy results. MATERIALS AND METHODS. We retrospectively included 389 patients (mean age ± SD, 62 ± 12 years old) who had undergone US-guided liver biopsy of 405 liver lesions between January 1, 2013, and June 30, 2015. We collected multiple patient- and procedure-related variables. By comparing pathology reports of biopsy and the reference standard (further histology or imaging follow-up), we were able to categorize the biopsy r…

AdultImage-Guided BiopsyMalemedicine.medical_specialtyRadiology Nuclear Medicine and ImagingFalse Negative Result030218 nuclear medicine & medical imaging03 medical and health sciencesCore biopsyFalse-negative result0302 clinical medicineBiopsymedicineHumansFalse Negative ReactionsUltrasonography InterventionalAgedRetrospective StudiesAged 80 and overFine-needle aspirationmedicine.diagnostic_testUS-guided liver biopsybusiness.industryLiver DiseasesDecision TreesUltrasoundnutritional and metabolic diseasesGeneral MedicineMiddle AgedPatient managementDiagnostic errorFine-needle aspiration030220 oncology & carcinogenesisLiver biopsyFemaleRadiologybusinessCore biopsyDecision tree model
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Development of a Peptide-Based Sandwich Elisa for Human Tissue Prokallikrein with No Cross-Reactivity from Mature Kallikrein

2000

Human tissue prokallikrein is the enzymatically inactive zymogen of a serine proteinase involved in the liberation of vasoactive kinin peptides, and it is supposed that an impaired prokallikrein-to-kallikrein conversion is closely related to certain hypertensive and inflammatory disorders. Progress in understanding the biological role of the proenzyme has been limited by the absence of an accurate assay for the kallikrein precursor. We describe a sandwich enzyme-linked immunosorbent assay to measure human tissue prokallikrein using monospecific anti-peptide antibodies raised against propeptide derivatives. This method could detect a minimum concentration of 60 pg/ml prokallikrein and displa…

AdultImmunologyTissue kallikreinEnzyme-Linked Immunosorbent AssayPeptideCross Reactionsmedicine.disease_causeSensitivity and SpecificityCross-reactivityZymogenmedicineHumansProtein precursorPharmacologychemistry.chemical_classificationEnzyme Precursorsmedicine.diagnostic_testChemistryReproducibility of ResultsKallikreinKininMolecular biologyPeptide FragmentsBiochemistryImmunoassayKallikreinsJournal of Immunoassay
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