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https://www.readbyqxmd.com/read/29055166/drug-monitoring-of-sunitinib-in-patients-with-advanced-solid-tumors-a-monocentric-observational-french-study
#1
Luc Cabel, Benoit Blanchet, Audrey Thomas-Schoemann, Olivier Huillard, Audrey Bellesoeur, Anatole Cessot, Julie Giroux, Pascaline Boudou-Rouquette, Romain Coriat, Michel Vidal, Nathaniel E B Saidu, Lisa Golmard, Jérome Alexandre, Francois Goldwasser
Therapeutic drug monitoring (TDM) could be helpful in oral targeted therapies. Data are sparse to evaluate its impact on treatment management. This study aimed to determine a threshold value of plasma drug exposure associated with the occurrence of grade 3-4 toxicity, then the potential impact of TDM on clinical decision. Consecutive outpatients treated with sunitinib were prospectively monitored between days 21-28 of the first cycle, then monthly until disease progression. At each consultation, the composite AUCƬ,ss (sunitinib + active metabolite SU12662) was assayed...
October 21, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29055164/reflectance-confocal-microscopy-identification-of-subclinical-basal-cell-carcinomas-during-and-after-vismodegib-treatment
#2
Caroline Couzan, Elisa Cinotti, Bruno Labeille, Paul Vercherin, Pietro Rubegni, Frédéric Cambazard, Jean Luc Perrot
BACKGROUND: Recently, it has been shown that reflectance confocal microscopy (RCM) could identify subclinical basal cell carcinoma (BCC) during vismodegib treatment of locally-advanced BCC. OBJECTIVES: To evaluate specificity and sensitivity of clinical, dermoscopic and RCM examination for BCC in patients with multiple BCCs treated by vismodegib. METHODS: 94 BCCs had 710 clinical, dermoscopic and RCM examinations during 72 weeks of vismodegib treatment...
October 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29055158/a-phase-2a-randomized-controlled-study-to-evaluate-the-pharmacokinetic-safety-tolerability-and-clinical-effect-of-topically-applied-umeclidinium-in-subjects-with-primary-axillary-hyperhidrosis
#3
A Nasir, R Bissonnette, C Maari, J DuBois, T Pene Dumitrescu, J Haddad, Y Yamaguchi, M Dalessandro
BACKGROUND: Hyperhidrosis is a common medical condition which can have a significant impact on quality of life. Umeclidinium (UMEC) is a long acting muscarinic antagonist (LAMA) developed as a dermal formulation. OBJECTIVES: This 2-week, double-blind, randomized, vehicle-controlled study evaluated systemic exposure, safety, and tolerability of topically administered UMEC in subjects with primary axillary hyperhidrosis. Clinical effect was a secondary objective, measured by gravimetry and the hyperhidrosis disease severity scale (HDSS)...
October 21, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29055125/vascular-endothelial-growth-factor-vegf-related-single-nucleotide-polymorphisms-rs10738760-and-rs6921438-are-not-associated-with-diabetic-retinopathy-dr-in-slovenian-patients-with-type-2-diabetes-mellitus-t2dm
#4
Rifet Terzić, Ines Cilenšek, Ruda Zorc Pleskovič, Sara Mankoč, Aleksandra Milutinović
Diabetic retinopathy (DR) is a complication of diabetes characterized by vascular permeability, increased tissue ischemia, and angiogenesis. One of the most important proteins involved in angiogenesis is vascular endothelial growth factor (VEGF, also known as VEGFA). A previous study demonstrated that two single nucleotide polymorphisms (SNPs), rs6921438 and rs10738760, account for nearly half the variation in circulating VEGF levels. The aim of our study was to assess the association between rs6921438 and rs10738760 and DR in Slovenian patients with type 2 diabetes mellitus (T2DM)...
October 20, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29055113/accelerating-patient-access-to-novel-biologics-using-stable-pool-derived-product-for-non-clinical-studies-and-single-clone-derived-product-for-clinical-studies
#5
Trent P Munro, Kim Le, Huong Le, Li Zhang, Jennitte Stevens, Neil Soice, Sabrina A Benchaar, Robert W Hong, Chetan T Goudar
Cell cloning and subsequent process development activities are on the critical path directly impacting the timeline for advancement of next generation therapies to patients with unmet medical needs. The use of stable cell pools for early stage material generation and process development activities is an enabling technology to reduce timelines. To successfully use stable pools during development, it is important that bioprocess performance and requisite product quality attributes be comparable to those observed from clonally derived cell lines...
October 21, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/29055072/reproductive-outcome-of-women-with-congenital-uterine-anomalies-after-assisted-reproduction-a-prospective-observational-study
#6
Matthew Prior, Alison Richardson, Sonia Asif, Lukasz Polanski, Michelle Parris-Larkin, Jane Chandler, Lynne Fogg, Pooja Jassal, Jim G Thornton, Nick J Raine-Fenning
OBJECTIVE: To assess the effect on reproductive outcome of congenital uterine anomalies in subfertile women in women undergoing assisted reproduction. METHODS: All women referred with subfertility between May 2009 and November 2015 who underwent assisted reproduction. As part of their initial assessment each woman was assessed by pelvic three-dimensional ultrasonography. The uterine morphology was classified using the modified American Fertility Society (AFS) classification of congenital anomalies...
October 21, 2017: Ultrasound in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29055041/the-possible-clinical-impact-of-risperidone-on-p-glycoprotein-mediated-transport-of-tacrolimus-a-case-report-and-in-vitro-study
#7
Nao Watanabe, Hiroki Higashi, Saki Nakamura, Keiko Nomura, Yuichi Adachi, Masato Taguchi
The authors encountered the case of an 8-fold increase in the concentration/dose (C/D) ratio of tacrolimus (TAC) following the coadministration of voriconazole (VRCZ) in a hematopoietic stem cell transplantation (HSCT) recipient. The interaction observed was much greater than expected and the patient had also been treated with oral risperidone (RSP). We hypothesized that cytochrome P450 (CYP)3A inhibition of the small intestine by VRCZ and P-glycoprotein (P-gp) inhibition of the small intestine by RSP exerted a synergistic effect on the bioavailability of TAC...
October 20, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29054982/discovery-of-a-highly-selective-nampt-inhibitor-that-demonstrates-robust-efficacy-and-improved-retinal-toxicity-with-nicotinic-acid-co-administration
#8
Genshi Zhao, Colin F Green, Yu-Hua Hui, Lourdes Prieto, Robert Shepard, Sucai Dong, Tao Wang, Bo Tan, Xueqian Gong, Lisa Kays, Robert L Johnson, Wenjuan Wu, Shobha Bhattachar, Miriam Del Prado, James R Gillig, Maria-Carmen Fernandez, Ken D Roth, Sean Buchanan, Ming-Shang Kuo, Sandaruwan Geeganage, Timothy P Burkholder
NAMPT, an enzyme essential for NAD+ biosynthesis, has been extensively studied as an anti-cancer target for developing potential novel therapeutics. Several NAMPT inhibitors have been discovered, some of which have been subjected to clinical investigations. Yet, the on-target hematological and retinal toxicities have hampered their clinical development. In this study, we report the discovery of a unique NAMPT inhibitor, LSN3154567. This molecule is highly selective, and has a potent and broad spectrum of anti-cancer activity...
October 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29054922/protein-turnover-measurements-in-human-serum-by-serial-immunoaffinity-lc-ms-ms
#9
Vahid Farrokhi, Xiaoying Chen, Hendrik Neubert
BACKGROUND: The half-life of target proteins is frequently an important parameter in mechanistic pharmacokinetic and pharmacodynamic (PK/PD) modeling of biotherapeutics. Clinical studies for accurate measurement of physiologically relevant protein turnover can reduce the uncertainty in PK/PD model-based predictions, for example, of the therapeutic dose and dosing regimen in first-in-human clinical trials. METHODS: We used a targeted mass spectrometry work flow based on serial immunoaffinity enrichment of multiple human serum proteins from a [5,5,5-(2)H3]-L-leucine tracer pulse-chase study in healthy volunteers...
October 20, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/29054907/secondary-aortoduodenal-fistula-and-the-unrecognised-herald-bleed
#10
Francesc Simó Alari, Esther Molina González, Israel Gutierrez, Aïcha Ahamdanech-Idrissi
A 65-year-old man with history of aortobifemoral surgery 4 years ago was admitted to hospital after sudden abdominal pain. Initially misdiagnosed as renal colic, he was treated with analgesics, and while on observation he started with haematemesis, rapidly responding to volume infusion. Upper gastrointestinal endoscopy showed fresh blood in the stomach with no visible active bleeding. CT scan showed an important contrast extravasation from the aorta to the third duodenal portion, restarting haemodynamic instability and a cardiac arrest...
October 20, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/29054884/assessing-the-extent-of-non-aggressive-cancer-in-clinically-detected-stage-i-non-small-cell-lung-cancer
#11
Minal S Kale, Keith Sigel, Grace Mhango, Juan P Wisnivesky
BACKGROUND: Overdiagnosis among clinically detected lung cancers likely consists of cases that are non-aggressive and slowly progressive and will never disseminate, cause symptoms or be a threat to a subject's survival, even if untreated. In this study, we estimate the prevalence of non-aggressive lung cancers from a large, population-based cancer registry. METHODS: We identified individuals ≥65 years with histologically confirmed, untreated stage I non-small cell lung cancers (NSCLCs) from the Surveillance, Epidemiology, and End Results-Medicare registry...
October 20, 2017: Thorax
https://www.readbyqxmd.com/read/29054878/pathological-tau-strains-from-human-brains-recapitulate-the-diversity-of-tauopathies-in-non-transgenic-mouse-brain
#12
Sneha Narasimhan, Jing L Guo, Lakshmi Changolkar, Anna Stieber, Jennifer D McBride, Luisa V Silva, Zhuohao He, Bin Zhang, Ronald J Gathagan, John Q Trojanowski, Virginia M Y Lee
Pathological tau aggregates occur in Alzheimer's disease (AD) and other neurodegenerative tauopathies. It is not clearly understood why tauopathies vary greatly in the neuroanatomical and histopathological patterns of tau aggregation, which contribute to clinical heterogeneity in these disorders. Recent studies have shown that tau aggregates may form distinct structural conformations, known as tau strains. Here, we developed a novel model to test the hypothesis that cell-to-cell transmission of different tau strains occurs in non-transgenic (non-Tg) mice, and to investigate whether there are strain-specific differences in the pattern of tau transmission...
October 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29054842/acute-biventricular-mechanical-circulatory-support-for-cardiogenic-shock
#13
Sudeep Kuchibhotla, Michele L Esposito, Catalina Breton, Robert Pedicini, Andrew Mullin, Ryan O'Kelly, Mark Anderson, Dennis L Morris, George Batsides, Danny Ramzy, Mark Grise, Duc Thinh Pham, Navin K Kapur
BACKGROUND: Biventricular failure is associated with high in-hospital mortality. Limited data regarding the efficacy of biventricular Impella axial flow catheters (BiPella) support for biventricular failure exist. The aim of this study was to explore the clinical utility of percutaneously delivered BiPella as a novel acute mechanical support strategy for patients with cardiogenic shock complicated by biventricular failure. METHODS AND RESULTS: We retrospectively analyzed data from 20 patients receiving BiPella for biventricular failure from 5 tertiary-care hospitals in the United States...
October 20, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29054821/an-in-vitro-experiment-to-simulate-how-easy-tablets-are-to-swallow
#14
M Marconati, S Raut, A Burbidge, J Engmann, M Ramaioli
The compliance of patients to solid oral dosage forms is heavily conditioned by the perceived ease of swallowing, especially in geriatric and pediatric populations. This study proposes a method, based on an in vitro model of the human oropharyngeal cavity, to quantitatively study the oral phase of human swallowing in presence of single or multiple tablets. The dynamics of swallowing was investigated varying the size and shape of model tablets and adjusting the applied force to the mechanical setup to simulate tongue pressure variations among individuals...
October 17, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29054772/through-clinical-observation-the-history-of-priapism-after-spinal-cord-injuries
#15
REVIEW
Mihaela Dana Turliuc, Serban Turliuc, Andrei Ionut Cucu, Camelia Tamas, Alexandru Carauleanu, Catalin Buzduga, Anca Sava, Gabriela Florenta Dumitrescu, Claudia Florida Costea
Since ancient times, the physicians of Antiquity noted the occurrence of priapism in some spinal cord injuries. Although priests saw it as a consequence of curses and witchcraft, after clinical observations of the Middle Ages and Renaissance, first medical hypotheses emerged in the 17(th)-19(th) centuries completed and argued by neuroscience and neurology developed in the European laboratories and hospitals. This study aims to present a short overview of the history of clinical observations of posttraumatic male priapism after spinal cord injuries since Antiquity until the beginning of the 20(th) century...
October 17, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/29054612/dihydropyrimidinase-deficiency-in-four-east-asian-patients-due-to-novel-and-rare-dpys-mutations-affecting-protein-structural-integrity-and-catalytic-activity
#16
Yoko Nakajima, Judith Meijer, Doreen Dobritzsch, Tetsuya Ito, Chunhua Zhang, Xu Wang, Yoriko Watanabe, Kyoko Tashiro, Rutger Meinsma, Jeroen Roelofsen, Lida Zoetekouw, André B P van Kuilenburg
Dihydropyrimidinase (DHP) is the second enzyme of the pyrimidine degradation pathway and catalyzes the ring opening of 5,6-dihydrouracil and 5,6-dihydrothymine. To date, only 31 genetically confirmed patients with a DHP deficiency have been reported and the clinical, biochemical and genetic spectrum of DHP deficient patients is, therefore, still largely unknown. Here, we show that 4 newly identified DHP deficient patients presented with strongly elevated levels of 5,6-dihydrouracil and 5,6-dihydrothymine in urine and a highly variable clinical presentation, ranging from asymptomatic to infantile spasm and reduced white matter and brain atrophy...
October 12, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29054589/baseline-asthma-burden-comorbidities-and-biomarkers-in-omalizumab-treated-patients-in-prospero
#17
Bradley E Chipps, Robert S Zeiger, Allan T Luskin, William W Busse, Benjamin L Trzaskoma, Evgeniya N Antonova, Hooman Pazwash, Susan L Limb, Paul G Solari, Noelle M Griffin, Thomas B Casale
BACKGROUND: Patients included in clinical trials do not necessarily reflect the real-world population. OBJECTIVE: To understand the characteristics, including disease and comorbidity burden, of patients with asthma receiving omalizumab in a real-world setting. METHODS: The Prospective Observational Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab (PROSPERO) was a US-based, multicenter, single-arm, and prospective study...
October 17, 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/29054515/blood-transfusion-management-and-transfusion-related-outcomes-in-daratumumab-treated-patients-with-relapsed-or-refractory-multiple-myeloma
#18
Ajai Chari, Suzanne Arinsburg, Sundar Jagannath, Toshihisa Satta, Ivey Treadwell, Donna Catamero, Gillian Morgan, Huaibao Feng, Clarissa Uhlar, Imran Khan, Parul Doshi, Saad Usmani
INTRODUCTION: Daratumumab, a human CD38 monoclonal antibody approved for multiple myeloma (MM) treatment, binds red blood cells (RBCs), resulting in panagglutination in compatibility tests. Published mitigation methods avoid additional testing, ensuring timely release of blood products. Blood transfusion management and transfusion-related outcomes of daratumumab-treated patients in the SIRIUS study are reported, with emphasis on 2 clinical sites. PATIENTS AND METHODS: Patients had MM treated with ≥ 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or were refractory to a proteasome inhibitor and an immunomodulatory drug...
September 19, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29054487/patterns-of-self-care-and-clinical-events-in-a-cohort-of-adults-with-heart-failure-1-year-follow-up
#19
Christopher S Lee, Julie T Bidwell, Marco Paturzo, Rosaria Alvaro, Antonello Cocchieri, Tiny Jaarsma, Anna Strömberg, Barbara Riegel, Ercole Vellone
BACKGROUND: Heart failure (HF) self-care is important in reducing clinical events (all-cause mortality, emergency room visits and hospitalizations). HF self-care behaviors are multidimensional and include maintenance (i.e. daily adherence behaviors), management (i.e. symptom response behaviors) and consulting behaviors (i.e. contacting a provider when appropriate). Across these dimensions, patterns of successful patient engagement in self-care have been observed (e.g. successful in one dimension but not in others), but no previous studies have linked patterns of HF self-care to clinical events...
October 17, 2017: Heart & Lung: the Journal of Critical Care
https://www.readbyqxmd.com/read/29054474/deubiquitylating-enzymes-as-cancer-stem-cell-therapeutics
#20
REVIEW
Saba Haq, Bharathi Suresh, Suresh Ramakrishna
The focus of basic and applied research on core stem cell transcription factors has paved the way to initial delineation of their characteristics, their regulatory mechanisms, and the applicability of their regulatory proteins for protein-induced pluripotent stem cells (protein-IPSC) generation and in further clinical settings. Striking parallels have been observed between cancer stem cells (CSCs) and stem cells. For the maintenance of stem cells and CSC pluripotency and differentiation, post translational modifications (i...
October 17, 2017: Biochimica et Biophysica Acta
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