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https://www.readbyqxmd.com/read/28329898/-analysis-of-secondary-data-to-determine-the-prevalence%C3%A2-of%C3%A2-cardiovascular-high-risk-patients-with-hypercholesterolemia-and-refractory-course-of-treatment
#1
Franz-Werner Dippel, Klaus G Parhofer, Thomas Müller-Bohn, Steffen Gebhardt, Karel Kostev
Background Hypercholesterolemia plays a causal role in the development of cardiovascular diseases. Patients are affected differently. There is a lack of epidemiological data about the frequence and characteristics of patients in Germany, especially about those who do not respond sufficiently to high intensity statins with or without other lipid modifying therapies. Methods From more than 2.6 million patient records of office based general practitioners, patients with hypercholestrolemia and high cardiovascular risk, who do not reach their individual LDL-C goal despite a best supplied twelve month maximum lipid lowering therapy (MPR ≥ 80 %), were extracted from the database...
March 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28329870/application-of-imaging-techniques-to-cases-of-drug-induced-crystal-nephropathy-in-preclinical-studies
#2
B Lenz, A Brink, M Siam, A De Paepe, S Bassett, A Eichinger-Chapelon, P Maliver, R Neff, U Niederhauser, B Steinhuber, R Zurbach, T Singer, C Funk, F Schuler, M Albassam, S Schadt
A number of drugs can cause precipitates within renal tubules leading to crystal nephropathy. Crystal nephropathy is usually an exposure-related finding and is not uncommon in preclinical studies, where high doses are tested. An understanding of the nature of precipitates is important for human risk assessment and further development. Our aim was to investigate the ability of various imaging techniques to detect the presence of drugs or metabolites in renal crystals. We applied matrix-assisted laser desorption/ionization - Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) imaging, Raman and infrared microspectroscopy, scanning electron microscopy coupled with energy dispersive X-ray (SEM/EDX) spectroscopy and standard histopathology to cases of drug-induced crystal nephropathy, induced in rodents and primates by four compounds...
February 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28329443/analyzing-the-potential-root-causes-of-variability-of-pharmacokinetics-in-preclinical-species
#3
Pierre Daublain, Kung-I Feng, Michael D Altman, Iain Martin, Suman Mukherjee, Rebecca Nofsinger, Alan B Northrup, Richard Tschirret-Guth, Mark Cartwright, Caroline McGregor
The purpose of this research was to assess variability in pharmacokinetic profiles (PK variability) in preclinical species and identify the risk factors associated with the properties of a drug molecule that contribute to the variability. Exposure data in mouse, rat, dog and monkey for a total of 16,592 research compounds studied between 1999 and 2013 were included in the analysis. Both in vivo study parameters and in silico/experimental physicochemical properties of the molecules were analyzed. Areas under the plasma concentration vs...
March 22, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28329346/posttreatment-reactions-after-single-dose-diethylcarbamazine-or-ivermectin-in-subjects-with-loa-loa-infection
#4
Jesica A Herrick, Fanny Legrand, Raceline Gounoue, Godwin Nchinda, Céline Montavon, Jean Bopda, Steve Mbickmen Tchana, Bienvenu Etogo Ondigui, Konrad Nguluwe, Michael P Fay, Michelle Makiya, Simon Metenou, Thomas B Nutman, Joseph Kamgno, Amy D Klion
Background.: Severe adverse reactions have been observed in individuals with Loa loa infection treated with either diethylcarbamazine (DEC), the drug of choice for loiasis, or ivermectin (IVM), which is used in mass drug administration programs for control of onchocerciasis and lymphatic filariasis in Africa. In this study, posttreatment clinical and immunologic reactions were compared following single-dose therapy with DEC or IVM to assess whether these reactions have the same underlying pathophysiology...
March 13, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28329286/short-course-tlr9-agonist-treatment-impacts-innate-immunity-and-plasma-viremia-in-individuals-with-hiv-infection
#5
Line Vibholm, Mariane H Schleimann, Jesper F Højen, Thomas Benfield, Rasmus Offersen, Katrine Rasmussen, Rikke Olesen, Anders Dige, Jørgen Agnholt, Judith Grau, Maria Buzon, Burghardt Wittig, Mathias Lichterfeld, Andreas Munk Petersen, Xutao Deng, Mohammed Abdel-Mohsen, Satish K Pillai, Sofie Rutsaert, Wim Trypsteen, Ward De Spiegelaere, Linos Vandekerchove, Lars Østergaard, Thomas A Rasmussen, Paul W Denton, Martin Tolstrup, Ole S Søgaard
Background: Treatment with latency reversing agents (LRA) enhances HIV-1 transcription in vivo but only leads to modest reductions in the size of the reservoir, possibly due to insufficient immune-mediated elimination of infected cells. We hypothesized that a single drug molecule - a novel toll-like receptor 9 (TLR9) agonist, MGN1703 - could function as an enhancer of innate immunity and an LRA in vivo. Methods: We conducted a single-arm, open-label study, where 15 virologically suppressed HIV-1 infected individuals on antiretroviral therapy received 60 mg MGN1703 s...
March 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28329062/comparison-of-demographic-and-photobiological-features-of-chronic-actinic-dermatitis-in-patients-with-lighter-vs-darker-skin-types
#6
Ki-Wei Tan, Ann K Haylett, Tsui C Ling, Lesley E Rhodes
Importance: Chronic actinic dermatitis (CAD) is classically described in older, white men, although increasing reports describe younger patients with darker skin types, particularly South Asians. Photocontact allergy occurs in CAD but is less studied than contact allergy in this exquisitely photosensitive condition. Objective: To evaluate for differences in demographic and photobiological features between persons with darker and lighter skin types who have CAD. Design, Setting, and Participants: This retrospective review included 70 consecutive adult patients (≥18 years) undergoing investigation for photosensitivity who were diagnosed with CAD from November 1, 2000, through August 31, 2015, at the specialist Photobiology Unit of a tertiary academic referral center...
March 22, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28328947/a-spontaneous-mutation-in-kdsd-a-biosynthesis-gene-for-3-deoxy-d-manno-octulosonic-acid-occurred-in-a-ciprofloxacin-resistant-strain-of-francisella-tularensis-and-caused-a-high-level-of-attenuation-in-murine-models-of-tularemia
#7
Taylor Chance, Jennifer Chua, Ronald G Toothman, Jason T Ladner, Jonathan E Nuss, Jo Lynne Raymond, Fabrice V Biot, Samandra Demons, Lynda Miller, Stephanie Halasohoris, Sherry Mou, Galina Koroleva, Sean Lovett, Gustavo Palacios, Nicholas J Vietri, Patricia L Worsham, Christopher K Cote, Todd M Kijek, Joel A Bozue
Francisella tularensis, a gram-negative facultative intracellular bacterial pathogen, is the causative agent of tularemia and able to infect many mammalian species, including humans. Because of its ability to cause a lethal infection, low infectious dose, and aerosolizable nature, F. tularensis subspecies tularensis is considered a potential biowarfare agent. Due to its in vitro efficacy, ciprofloxacin is one of the antibiotics recommended for post-exposure prophylaxis of tularemia. In order to identify therapeutics that will be efficacious against infections caused by drug resistant select-agents and to better understand the threat, we sought to characterize an existing ciprofloxacin resistant (CipR) mutant in the Schu S4 strain of F...
2017: PloS One
https://www.readbyqxmd.com/read/28328763/induration-at-injection-or-infusion-site-may-reduce-bioavailability-of-parenteral-phenobarbital-administration
#8
Hirokazu Nakayama, Hirotoshi Echizen, Ryuichi Ogawa, Atsuya Akabane, Toshiaki Kato, Takao Orii
BACKGROUND: Phenobarbital is well tolerated and effective for controlling agitation or preventing convulsion at the end of life. No information is available concerning parenteral bioavailability of phenobarbital when induration develops at injection or infusion site. We investigated whether induration at injection or infusion site is related to phenobarbital bioavailability via parenteral routes of continuous subcutaneous infusion and intermittent subcutaneous or intramuscular injection...
March 21, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28328762/a-significant-influence-of-metronidazole-on-busulfan-pharmacokinetics-a-case-report-of-therapeutic-drug-monitoring
#9
Hyewon Chung, Kyung-Sang Yu, Kyung Taek Hong, Jung Yoon Choi, Che Ry Hong, Hyoung Jin Kang, Kyung Duk Park, Hee Young Shin, SeungHwan Lee
Busulfan is a cytotoxic agent used in preconditioning for hematopoietic stem cell transplantation (HSCT). Therapeutic drug monitoring of busulfan is necessary owing to its narrow therapeutic range. Patients undergoing preconditioning are susceptible to infection and might require co-administration of antibiotics. We present a case study of a three-year-old girl with precursor T-cell acute lymphoblastic leukemia who received intravenous busulfan before HSCT. Metronidazole was co-administered before the third dose of busulfan because of Clostridium difficile infection...
March 21, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28328695/effect-of-biperiden-treatment-in-acute-orofacial-and-extremity-dyskinesia-with-methylphenidate-therapy
#10
Elif Acar Arslan, Erhan Arslan, Anil Kilinç, Özkan Göksu
Methylphenidate is a stimulant drug commonly prescribed to individuals with attention-deficit/hyperactivity disorder. The suggested underlying mechanism of acute dyskinesias is dopaminergic transmission increase. We describe a 9-year-old boy with a diagnosis of attention-deficit/hyperactivity disorder admitted to emergency clinic with primarily orofacial and extremity dyskinesia after administration of a first dose of 18 mg OROS (osmotic [controlled] release oral) methylphenidate (Concerta). OROS methylphenidate was discontinued, and the patient's symptoms resolved within 20 minutes after injection of biperiden by intravenous route (0...
March 21, 2017: Pediatric Emergency Care
https://www.readbyqxmd.com/read/28328548/characterization-of-hiv-seroconverters-in-a-tdf-ftc-prep-study-hptn-067-adapt
#11
Mariya V Sivay, Maoji Li, Estelle Piwowar-Manning, Yinfeng Zhang, Sarah E Hudelson, Mark A Marzinke, Rivet K Amico, Andrew Redd, Craig W Hendrix, Peter L Anderson, Kevin Bokoch, Linda Gail-Bekker, Frits van Griensven, Sharon Mannheimer, James P Hughes, Robert Grant, Susan H Eshleman
BACKGROUND: HPTN 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in women (South Africa) and men who have sex with men (Thailand, US). Participants received once-weekly directly observed TDF/FTC (DOT), and were then randomized to daily, time-driven, or event-driven PrEP. This report describes characterization of 12 HIV seroconversion events in this trial. METHODS: HIV rapid testing was performed at study sites...
March 22, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28328286/identification-of-the-minimum-effective-dose-for-normally-distributed-data-using-a-bayesian-variable-selection-approach
#12
Martin Otava, Ziv Shkedy, Ludwig A Hothorn, Willem Talloen, Daniel Gerhard, Adetayo Kasim
The identification of the minimum effective dose is of high importance in the drug development process. In early stage screening experiments, establishing the minimum effective dose can be translated into a model selection based on information criteria. The presented alternative, Bayesian variable selection approach, allows for selection of the minimum effective dose, while taking into account model uncertainty. The performance of Bayesian variable selection is compared with the generalized order restricted information criterion on two dose-response experiments and through the simulations study...
February 16, 2017: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/28328081/btk-inhibition-is-a-potent-approach-to-block-ige-mediated-histamine-release-in-human-basophils
#13
Dubravka Smiljkovic, Katharina Blatt, Gabriele Stefanzl, Yulia Dorofeeva, Cathrin Skrabs, Margarete Focke-Tejkl, Wolfgang R Sperr, Ulrich Jaeger, Rudolf Valenta, Peter Valent
BACKGROUND: Recent data suggest that Bruton's tyrosine kinase (BTK) is an emerging therapeutic target in IgE receptor (IgER) cross-linked basophils. METHODS: We examined the effects of four BTK inhibitors (ibrutinib, dasatinib, AVL-292, CNX-774) on IgE-dependent activation and histamine release in blood basophils obtained from allergic patients (n=11) and non-allergic donors (n=5). In addition, we examined the effects of these drugs on the growth of the human basophil cell line KU812 and the human mast cell line HMC-1...
March 22, 2017: Allergy
https://www.readbyqxmd.com/read/28328034/extraction-efficiency-and-implications-for-absolute-quantitation-of-propranolol-in-mouse-brain-liver-and-kidney-tissue-sections-using-droplet-based-liquid-microjunction-surface-sampling-high-performance-liquid-chromatography-electrospray-ionization-tandem-mass
#14
Vilmos Kertesz, Taylor M Weiskittel, Marissa Vavrek, Carol Freddo, Gary J Van Berkel
RATIONALE: Currently, the absolute quantitation aspects of droplet-based surface sampling for tissue analysis using a fully automated autosampler/high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS) system have not been fully evaluated. Knowledge of extraction efficiency and its reproducibility is required to judge the potential of the method for absolute quantitation of analytes from tissue sections. METHODS: Adjacent tissue sections of propranolol-dosed mouse brain (10-μm-thick), kidney (10-μm-thick) and liver (8-, 10-, 16- and 24-μm-thick) were obtained...
July 30, 2016: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28328020/detection-of-glutathione-conjugates-of-amiodarone-and-its-reactive-diquinone-metabolites-in-rat-bile-using-mass-spectrometry-tools
#15
Keyur R Parmar, Shalu Jhajra, Saranjit Singh
RATIONALE: Amiodarone is reported to cause hepato and pulmonary toxicity in humans, which has been envisaged to be due to formation of its reactive metabolites, essentially based on its structural similarity to benzbromarone, a drug withdrawn from the market due to reasons of similar hepatotoxicity. Therefore, the purpose of this study was to detect glutathione conjugates of amiodarone and its reactive diquinone metabolites in rat bile using mass spectrometry tools. METHODS: Wistar rats were dosed orally with an amiodarone suspension and bile was collected via bile duct cannulation followed by solid-phase extraction, protein precipitation and centrifugation...
May 30, 2016: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28327820/adverse-systemic-reaction-to-benznidazole
#16
María Verónica Pacheco Coronel, Laura Oriente Frutos, Eva Calabuig Muñoz, Diana Kury Valle, Dolores Hernández Fernández de Rojas
Benznidazole, drug of choice for Chagas disease (CD), has been associated with a high incidence of adverse reactions that can become serious, necessitating discontinuation of the drug. We describe the case of a Bolivian patient living in Spain for 9 years, who, following treatment with benznidazole for CD in indeterminate chronic phase, presented with fever, skin lesions, digestive symptoms, general malaise, and laboratory abnormalities. After the discontinuation of benznidazole and, the intake of antihistamines and systemic corticosteroids, the patient presented a complete resolution of the symptoms...
January 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28327785/ultrastructural-alterations-in-schistosoma-mansoni-juvenile-and-adult-male-worms-after-in-vitro-incubation-with-primaquine
#17
Reem Osama A Kamel, Fatma El-Zahraa Anwar Bayaumy
BACKGROUND: Praziquantel has been cited as the only drug for treating schistosomiasis. However, concerns over drug resistance have encouraged the search for novel drug leads. The antimalarial drug primaquine possesses interesting anti-schistosmal properties. OBJECTIVES: This study is the first to document the potential role of primaquine as a schistosomicide and the ultrastructural changes induced by primaquine on juvenile or adult male worms of Schistosoma mansoni...
April 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28327425/protein-drug-nanoconjugates-finding-the-alternative-proteins-as-drug-carrier
#18
Iqra Munir, Sadia Ajmal, Muhammad Raza Shah, Aftab Ahmad, Abdul Hameed, Syed Abid Ali
Present study was conducted to establish the interaction of bovine fetuin-A to validate its binding modalities with doxorubicin (Dox). Fetuin-A was purified to highest purity and monodispersity. Green synthesis of fetuin-A conjugated gold nanoparticles (F-GNPs) have been performed giving typical UV-maxima with subtle variation in fourier transform infrared spectroscopy (FTIR). Atomic force microscopy (AFM) revealed spherical shaped, polydisperse F-GNPs of varying sizes, complementing the radius of hydration (19...
March 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28327340/epileptic-activity-in-alzheimer-s-disease-causes-and-clinical-relevance
#19
REVIEW
Keith A Vossel, Maria C Tartaglia, Haakon B Nygaard, Adam Z Zeman, Bruce L Miller
Epileptic activity is frequently associated with Alzheimer's disease; this association has therapeutic implications, because epileptic activity can occur at early disease stages and might contribute to pathogenesis. In clinical practice, seizures in patients with Alzheimer's disease can easily go unrecognised because they usually present as non-motor seizures, and can overlap with other symptoms of the disease. In patients with Alzheimer's disease, seizures can hasten cognitive decline, highlighting the clinical relevance of early recognition and treatment...
April 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28327122/midodrine-as-adjunctive-support-for-treatment-of-refractory-hypotension-in-the-intensive-care-unit-a-multicenter-randomized-placebo-controlled-trial-the-midas-trial
#20
Matthew H Anstey, Bradley Wibrow, Tharusan Thevathasan, Brigit Roberts, Khushi Chhangani, Pauline Yeung Ng, Alexander Levine, Alan DiBiasio, Todd Sarge, Matthias Eikermann
BACKGROUND: Patients admitted to intensive care units (ICU) are often treated with intravenous (IV) vasopressors. Persistent hypotension and dependence on IV vasopressors in otherwise resuscitated patients lead to delay in discharge from ICU. Midodrine is an oral alpha-1 adrenergic agonist approved for treatment of symptomatic orthostatic hypotension. This trial aims to evaluate whether oral administration of midodrine is an effective adjunct to standard therapy to reduce the duration of IV vasopressor treatment, and allow earlier discharge from ICU and hospital...
March 21, 2017: BMC Anesthesiology
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