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First-in-Human Phase I Study of Lumretuzumab, a Glycoengineered Humanized Anti-HER3 Monoclonal Antibody, in Patients with Metastatic or Advanced HER3…

2016

Abstract Purpose: A first-in-human phase I study was conducted to characterize safety, efficacy, and pharmacokinetic (PK) and pharmacodynamic (PD) properties of lumretuzumab, a humanized and glycoengineered anti-HER3 monoclonal antibody, in patients with advanced cancer. Experimental Design: Twenty-five patients with histologically confirmed HER3-expressing tumors received lumretuzumab (100, 200, 400, 800, 1,600, and 2,000 mg) every two weeks (q2w) in 3+3 dose-escalation phase. In addition, 22 patients were enrolled into an extension cohort at 2,000 mg q2w. Results: There were no dose-limiting toxicities. Common adverse events (any grade) included diarrhea (22 patients, 46.8%), fatigue (21 …

AdultMale0301 basic medicineCancer Researchmedicine.medical_specialtyPathologyMaximum Tolerated DoseReceptor ErbB-3CmaxAntibodies Monoclonal HumanizedResearch SupportGastroenterologyClinical Trial Phase I03 medical and health sciencesPhase I0302 clinical medicinePharmacokineticsInternal medicineJournal ArticlemedicineHumansNon-U.S. Gov'tAdverse effectAgedAnalgesicsbusiness.industryResearch Support Non-U.S. Gov'tCancerMiddle AgedLumretuzumabmedicine.diseaseClinical TrialMulticenter StudyTreatment Outcome030104 developmental biologyOncology030220 oncology & carcinogenesisPharmacodynamicsMonoclonalFemaleColorectal NeoplasmsbusinessEx vivo
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Contact dermatitis due to nickel allergy in patients suffering from non-celiac wheat sensitivity

2017

Background: Non‐celiac wheat sensitivity (NCWS) is a new clinical entity in the world of gluten‐related diseases. Nickel, the most frequent cause of contact allergy, can be found in wheat and results in systemic nickel allergy syndrome and mimics irritable bowel syndrome (IBS). Objective: To evaluate the frequency of contact dermatitis due to nickel allergy in NCWS patients diagnosed by a double‐blind placebo‐controlled(DBPC)challenge,and to identify the characteristics of NCWS patients with nickel allergy. Methods: We performed a prospective study of 60 patients (54 females, 6 males; mean age 34.1 ± 8.1 years) diagnosed with NCWS from December 2014 to November 2016; 80 age‐ and sex‐matched…

AdultMale0301 basic medicineNickel allergymedicine.medical_specialtyLetterSettore MED/09 - Medicina InternaNon-celiac wheat sensitivitynon-celiac wheat insensitivityNickel allergyWheat HypersensitivityArticlecutaneous symptoms03 medical and health sciences0302 clinical medicineDouble-Blind MethodNickelHypersensitivitymedicineCutaneous symptomHumansIngestionIn patientProspective StudiesProspective cohort studysystemic nickel allergy syndromeTriticumIrritable bowel syndromeNutrition and Dieteticsbusiness.industryCase-control studyPatch testnon‐celiac  wheat  sensitivity;  nickel  allergy;  cutaneous  symptoms;  irritable  bowel  syndromeCutaneous symptoms; Irritable bowel syndrome; Nickel allergy; Non-celiac wheat sensitivity; Food SciencePatch Testsmedicine.diseaseintradermal testingDermatologySurgeryIrritable bowel syndromenickel allergy ; non-celiac wheat sensitivity ; irritable bowel syndrome ; cutaneous symptoms030104 developmental biologyCase-Control StudiesDermatitis Allergic ContactFemale030211 gastroenterology & hepatologybusinessContact dermatitisFood Science
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Treatment response to dimethyl fumarate is characterized by disproportionate CD8+ T cell reduction in MS

2017

Background: The effect of dimethyl fumarate (DMF) on circulating lymphocyte subsets and their contribution as predictors of clinical efficacy have not yet been investigated in multiple sclerosis (MS). Objective: To evaluate lymphocytes and lymphocyte subsets (analyzed 6 months after DMF start) in MS patients with and without disease activity after 1 year of treatment in a retrospective study. Methods: Peripheral blood lymphocyte subsets were analyzed by flow cytometry. Untreated MS patients ( n = 40) were compared to those 6 months after onset of DMF treatment ( n = 51). Clinical and magnetic resonance imaging (MRI) disease activity of DMF-treated patients were assessed in the first year un…

AdultMale0301 basic medicineTreatment responseMultiple SclerosisAdolescentDimethyl FumarateAntigens CD19CD4-CD8 RatioCD8-Positive T-LymphocytesPharmacologyStatistics NonparametricReduction (complexity)Young Adult03 medical and health scienceschemistry.chemical_compound0302 clinical medicineText miningLymphopeniamedicineHumansCytotoxic T cellLongitudinal StudiesLymphocyte CountClinical efficacyRetrospective StudiesB-LymphocytesDimethyl fumarateChemistrybusiness.industryMultiple sclerosisMiddle AgedFlow Cytometrymedicine.diseaseMagnetic Resonance ImagingCross-Sectional StudiesTreatment Outcome030104 developmental biologyROC CurveNeurologyDisease ProgressionFemaleNeurology (clinical)businessImmunosuppressive Agents030217 neurology & neurosurgeryFollow-Up StudiesLymphocyte subsetsMultiple Sclerosis Journal
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The rs2294918 E434K variant modulates patatin-like phospholipase domain-containing 3 expression and liver damage

2016

The patatin-like phosholipase domain-containing 3 (PNPLA3) rs738409 polymorphism (I148M) is a major determinant of hepatic fat and predisposes to the full spectrum of liver damage in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate whether additional PNPLA3 coding variants contribute to NAFLD susceptibility, first in individuals with contrasting phenotypes (with early-onset NAFLD vs. very low aminotransferases) and then in a large validation cohort. Rare PNPLA3 variants were not detected by sequencing coding regions and intron-exon boundaries either in 142 patients with early-onset NAFLD nor in 100 healthy individuals with alanine aminotransferase22/20 IU/mL. …

AdultMale0301 basic medicinemedicine.medical_specialtyAdolescentPolymorphism Single Nucleotide03 medical and health sciences0302 clinical medicineNon-alcoholic Fatty Liver DiseaseLipid dropletInternal medicineNonalcoholic fatty liver diseasemedicineHumansGenetic Predisposition to DiseaseAlleleChildGeneticsHepatologybiologyMembrane ProteinsAlanine TransaminaseLipaseMiddle AgedHepatologyLipid Metabolismmedicine.diseasedigestive system diseases030104 developmental biologyEndocrinologyHaplotypesLiverAlanine transaminasePatatin-like phospholipaseadolescent; adult; alanine transaminase; case-control studies; child; female; genetic predisposition to disease; haplotypes; humans; lipase; lipid metabolism; liver; male; membrane proteins; middle aged; non-alcoholic fatty liver disease; polymorphism; single nucleotide; hepatologyCase-Control Studiesbiology.proteinFemale030211 gastroenterology & hepatologySteatosisSteatohepatitis
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PTPN22 and CTLA-4 Polymorphisms Are Associated With Polyglandular Autoimmunity

2017

Context Single nucleotide polymorphisms (SNPs) of various genes increase susceptibility to monoglandular autoimmunity. Data on autoimmune polyglandular syndromes (APSs) are scarce. Objective Evaluate potential associations of eight SNPs with APSs. Setting Academic referral endocrine clinic. Patients A total of 543 patients with APS and monoglandular autoimmunity and controls. Intervention The SNP protein tyrosine phosphatase nonreceptor type 22 (PTPN22) rs2476601 (+1858); cytotoxic T-lymphocyte‒associated antigen 4 (CTLA-4) rs3087243 (CT60) and rs231775 (AG49); vitamin D receptor (VDR) rs1544410 (Bsm I), rs7975232 (Apa I), rs731236 (Taq I); tumor necrosis factor α rs1800630 (-863); and inte…

AdultMale0301 basic medicinemedicine.medical_specialtyGenotypeEndocrinology Diabetes and MetabolismGraves' diseaseClinical Biochemistry030209 endocrinology & metabolismSingle-nucleotide polymorphismPolymorphism Single NucleotideBiochemistryCalcitriol receptorPTPN22Young Adult03 medical and health sciences0302 clinical medicineEndocrinologyGene FrequencyInternal medicinemedicineHumansCTLA-4 AntigenGenetic Predisposition to DiseasePolyendocrinopathies AutoimmuneAllele frequencyGenetic Association Studiesbusiness.industryBiochemistry (medical)HaplotypeCase-control studyProtein Tyrosine Phosphatase Non-Receptor Type 22Odds ratioMiddle Agedmedicine.disease030104 developmental biologyEndocrinologyCase-Control StudiesFemalebusinessThe Journal of Clinical Endocrinology & Metabolism
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Angiopoietin-Like Protein 8 Is a Novel Vitamin D Receptor Target Gene Involved in Nonalcoholic Fatty Liver Pathogenesis

2018

Hepatic vitamin D receptor (VDR) expression is increased in patients with nonalcoholic fatty liver (NAFL) and is required for liver steatosis in an NAFL mouse model. However, how hepatocyte VDR is involved in setting up steatosis remains unclear. The authors transduced human hepatocyte-derived cells with an adenoviral vector encoding human VDR and found that angiopoietin-like protein 8 (ANGPTL8) expression was increased upon VDR activation by vitamin D or lithocholic acid. The mRNA levels of hepatic VDR- and vitamin D-related genes [cytochrome P450 (CYP) 2R1, CYP27A1, and CYP3A4] were higher in NAFL patients compared with normal liver subjects. Noteworthy, hepatic ANGPTL8 mRNA and protein l…

AdultMale0301 basic medicinemedicine.medical_specialtyLithocholic acidPeptide HormonesFatty Acids NonesterifiedCalcitriol receptorPathology and Forensic Medicine03 medical and health scienceschemistry.chemical_compound0302 clinical medicineAngiopoietin-Like Protein 8Non-alcoholic Fatty Liver DiseaseInternal medicineCYP27A1medicineHumansInsulinCells CulturedTriglyceridesGene knockdownCYP3A4Fatty liverMiddle Agedmedicine.diseaseAngiopoietin-like Proteins030104 developmental biologymedicine.anatomical_structureEndocrinologyGene Expression RegulationchemistryCase-Control StudiesHepatocyteHepatocytesReceptors CalcitriolFemale030211 gastroenterology & hepatologySteatosisThe American Journal of Pathology
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Measuring deterioration in international classification of functioning domains of people with multiple sclerosis who are ambulatory.

2007

Background and PurposeMeasures to detect important effects related to physical therapy interventions must be able to detect an important change. The purpose of this study was to select the most responsive physical functioning measures for multiple sclerosis (MS) using the International Classification of Functioning, Disability and Health (ICF) as a framework.SubjectsThe participants were 120 people with MS who were ambulatory from a population-based sample.MethodsPhysical functioning was assessed by quantitative clinical measures of activities (n=5) and body functions (n=7) and by self-reported performance in self-care, mobility, and domestic life domains in the activities and participation…

AdultMale030506 rehabilitationmedicine.medical_specialtyActivities of daily livingMultiple SclerosisPopulationPsychological interventionPhysical Therapy Sports Therapy and RehabilitationStatistics Nonparametric03 medical and health sciences0302 clinical medicinePhysical medicine and rehabilitationInternational Classification of Functioning Disability and HealthSurveys and QuestionnairesActivities of Daily LivingmedicineHumansDisabled Persons10. No inequalityeducationAgededucation.field_of_studyExpanded Disability Status ScaleReceiver operating characteristicMiddle AgedTest (assessment)Self CareROC CurveAmbulatoryPhysical therapyFemale0305 other medical sciencePsychology030217 neurology & neurosurgeryPhysical therapy
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Testing Individual Risk of Acute Mountain Sickness at Greater Altitudes

2009

The assessment of an individual's degree of acclimatization to altitude is difficult. This is particularly applicable to military operations that have to be performed at altitude. This study describes a new and simple test that allows for the determination of an individual's risk for high-altitude illness at higher altitudes. The prediction is based on the lowest oxygen saturation (SaO2) found during an uphill run at high altitude (11,060 ft [3,371 m]), combined with the time needed to complete the run. The test results were compared against the severity of high-altitude symptomatology on the summit of Mont Blanc (15,762 ft [4,808 m]). The main outcome was the significant correlation betwee…

AdultMaleAcclimatizationAltitude SicknessIndividual riskRisk AssessmentStatistics NonparametricRunningOxygen ConsumptionAltitudePredictive Value of TestsGermanySurveys and QuestionnairesTask Performance and AnalysisHumansMedicineOximetryMont blancOxygen saturation (medicine)business.industryAltitudePublic Health Environmental and Occupational HealthGeneral MedicineEffects of high altitude on humansMountaineeringMilitary PersonnelbusinessDemographyMilitary Medicine
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Metastatic Anterior Chamber Non-Hodgkin Lymphoma in a Patient With Acquired Immunodeficiency Syndrome

1997

Purpose To alert ophthalmologists to the possibility of metastatic anterior chamber intraocular non-Hodgkin lymphoma in patients with acquired immunodeficiency syndrome (AIDS). Methods We examined a 19-year-old man with AIDS who had an anterior uveitis with pseudohypopyon and a history of 2 months of malaise. A specimen of the lesion was obtained with a 25-gauge needle for pathologic examination. RESULTS: Systemic exploration showed hepatomegaly. Abdominal computed tomography showed multiple lesions in the liver and spleen. Fine-needle aspiration disclosed a high-grade non-Hodgkin lymphoma. The result of a fine-needle aspiration obtained from a lesion in the anterior chamber was consistent …

AdultMaleAcquired Immunodeficiency SyndromePathologymedicine.medical_specialtyAnterior Chamberbusiness.industryEye NeoplasmsLymphoma Non-HodgkinEye diseaseBiopsy Needlemedicine.diseaseLymphomaMetastasisMalaiseLesionOphthalmologyImmunopathologymedicineHumansmedicine.symptombusinessComplicationUveitisAmerican Journal of Ophthalmology
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Autoimmune associations and autoantibody screening show focused recognition in patient subgroups with generalized myasthenia gravis

2013

Autoimmune associations in myasthenia gravis (MG)-patients and their relatives have not been re-assessed since their separation into early- or late-onset MG (EOMG, LOMG), or thymoma-associated MG. Here, we analysed 226 EOMG-, 97 LOMG-, and 150 thymoma-patients for autoimmune disorders in themselves and their relatives. From 283 of them sera were tested for different organ- and non-organ-specific autoantibodies (autoAbs) by immunofluorescence test (IFT) and ELISA; genotyping was performed in 213 patients. Relatives with autoimmune disorders were reported by more patients with EOMG (40% of 210) than LOMG (20% of 89; p0.01) than thymomas (8% of 150; p0.001). In 150 genotyped EOMG-females, the …

AdultMaleAdolescentGenotypeThymomaAnti-nuclear antibodyImmunologyPTPN22Young AdultPrimary biliary cirrhosisPopulation GroupsMyasthenia GravismedicineHumansImmunology and AllergyAge of OnsetChildAgedAutoantibodiesAged 80 and overProtein Tyrosine Phosphatase Non-Receptor Type 2Neuromyelitis opticabusiness.industryMultiple sclerosisAutoantibodyGeneral MedicineMiddle Agedmedicine.diseaseMuscle StriatedMyasthenia gravisPedigreeOrgan SpecificityChild PreschoolRheumatoid arthritisImmunologyAdrenal CortexFemalebusinessHuman Immunology
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