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https://www.readbyqxmd.com/read/28528528/ustekinumab-a-review-in-moderate-to-severe-crohn-s-disease
#1
Yvette N Lamb, Sean T Duggan
Ustekinumab (Stelara(®)) has been recently approved in the EU and the USA as intravenous induction and subcutaneous maintenance therapy for adult patients with moderately to severely active Crohn's disease who have failed or were intolerant to treatment with immunomodulators, corticosteroids or at least one tumour necrosis factor (TNF) antagonist. Ustekinumab, a monoclonal antibody to the shared p40 subunit of the proinflammatory interleukin (IL)-12 and IL-23 cytokines, has a unique mechanism of action distinct from that of TNF antagonists...
May 20, 2017: Drugs
https://www.readbyqxmd.com/read/28528510/immunogenomics-using-genomics-to-personalize-cancer-immunotherapy
#2
Rance C Siniard, Shuko Harada
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy...
May 20, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28528469/multiple-sclerosis-treatment-with-fingolimod-profile-of-non-cardiologic-adverse-events
#3
REVIEW
Yara Dadalti Fragoso
Fingolimod was the first oral medication approved for management of multiple sclerosis and is currently used by tens of thousands patients worldwide. Fingolimod acts via the sphingosine 1-phosphate (S1P) receptor, maintaining peripheral lymphocytes entrapped in the lymph nodes. In consequence, there is a reduction in the infiltration of aggressive lymphocytes into the central nervous system. The drug is safe and effective, and its first hours of use are associated with related to S1P receptors in the heart...
May 20, 2017: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/28528358/dna-topoisomerase-targeting-chemotherapeutics-what-s-new
#4
REVIEW
Selma M Cuya, Mary-Ann Bjornsti, Robert C A M van Waardenburg
To resolve the topological problems that threaten the function and structural integrity of nuclear and mitochondrial genomes and RNA molecules, human cells encode six different DNA topoisomerases including type IB enzymes (TOP1 and TOP1mt), type IIA enzymes (TOP2α and TOP2β) and type IA enzymes (TOP3α and TOP3β). DNA entanglements and the supercoiling of DNA molecules are regulated by topoisomerases through the introduction of transient enzyme-linked DNA breaks. The covalent topoisomerase-DNA complexes are the cellular targets of a diverse group of cancer chemotherapeutics, which reversibly stabilize these reaction intermediates...
May 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28528303/discovery-of-a-potent-dual-alk-and-egfr-t790m-inhibitor
#5
Jaebong Jang, Jung Beom Son, Ciric To, Magda Bahcall, So Young Kim, Seock Yong Kang, Mierzhati Mushajiang, Younho Lee, Pasi A Jänne, Hwan Geun Choi, Nathanael S Gray
The mutational activations of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR) are validated oncogenic events and the targets of approved drugs to treat non-small cell lung cancer (NSCLC). Here we report highly potent dual small molecule inhibitors of both ALK and EGFR, particularly the T790M mutant which confers resistance to first generation EGFR inhibitors. Dual ALK/EGFR inhibitors may provide an efficient approach to prevent resistance that arises as a consequence of clinically reported reciprocal activation mechanisms...
May 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28528302/nanomolar-anti-sickling-compounds-identified-by-ligand-based-pharmacophore-approach
#6
Odailson Santos Paz, Milena de Jesus Pinheiro, Renan Fernandes do Espirito Santo, Cristiane Flora Villarreal, Marcelo Santos Castilho
Adenosine receptors are considered as potential targets for drug development against several diseases. The discovery of subtype 2B adenosine receptors role in erythrocyte sickling process proved its importance to neglected diseases such as sickle cell anemia, which affects approximately 29.000 people around the world, but whose treatment is restricted to just one FDA approved drug (hydroxyurea). In order to widen the therapeutic arsenal available to treat sickle cell anemia patients, it is imperative to identify new lead compounds that modify the sickling course and not just its symptoms...
May 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28528300/treating-metastatic-triple-negative-breast-cancer-with-cd44-neuropilin-dual-molecular-targets-of-multifunctional-nanoparticles
#7
De-Sheng Liang, Wen-Jie Zhang, Ai-Ting Wang, Hai-Tao Su, Hai-Jun Zhong, Xian-Rong Qi
Metastasis of cancer makes up the vast majority of cancer-related deaths, and it usually initiates from tumor cells invasiveness and develops through tumor neovasculature. In this work, we have fabricated a CD44/neuropilin dual receptor-targeting nanoparticulate system (tLyP-1-HT NPs) with endogenous or FDA approved components for treating metastatic triple negative breast cancer (TNBC). The enhanced specific targeting of tLyP-1-HT NPs to both metastatic tumor cells and metastasis-supporting tumor neovasculature was contributed by means of CD44/neuropilin dual receptor-mediated interaction...
May 13, 2017: Biomaterials
https://www.readbyqxmd.com/read/28528267/using-mri-to-non-invasively-and-accurately-quantify-preoperative-hepatic-steatosis
#8
Callisia N Clarke, Haesun Choi, Ping Hou, Catherine H Davis, Jingfei Ma, Asif Rashid, Jean-Nicolas Vauthey, Thomas A Aloia
BACKGROUND: The obesity epidemic has significantly increased the incidence and severity of hepatic steatosis in liver surgery patients and liver donors, potentially impacting postoperative liver regeneration and function. Development of a non-invasive means to quantify hepatic steatosis would facilitate selection of candidates for liver resection and transplant donation. METHODS: An IRB-approved protocol prospectively enrolled 28 patients with liver tumors requiring hepatic resection...
May 17, 2017: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/28527965/perfusion-index-an-indicator-of-success-during-endoscopic-thoracic-sympathectomy-for-hyperhidrosis
#9
Eric I-Hun Jeng, Nikolaus Gravenstein, Charles T Klodell
BACKGROUND: Endoscopic thoracic sympathectomy (ETS) is indicated for refractory hyperhidrosis. The pulse oximetry-derived perfusion index (PI) quantifies pulsatile blood flow at the oximeter. Thoracic sympathectomy increases blood flow; thus we postulate it will reliably increase PI. We evaluated the ipsilateral finger PI as a predictor of successful sympathectomy during ETS. METHODS: After institutional review board approval and informed consent, 100 adult patients undergoing bilateral ETS were studied...
May 17, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28527831/different-efficacy-of-inhaled-and-oral-medications-in-pulmonary-hypertension
#10
Batool J AbuHalimeh, Joseph G Parambil, Adriano R Tonelli
Pulmonary arterial hypertension (PAH) is progressive disorder characterized by elevated pulmonary vascular resistance that can lead to right heart failure and death. One of the main therapeutic options for PAH are medications targeting the prostacyclin pathway. Treprostinil is a prostacyclin analogue and selexipag is a selective IP receptor agonist. Treprostinil can be delivered by a variety of routes including oral, inhaled, subcutaneous and intravenous. Selexipag is currently approved as an oral formulation...
May 17, 2017: Heart & Lung: the Journal of Critical Care
https://www.readbyqxmd.com/read/28527633/anthelmintic-activity-of-cytochrome-p450-inhibitors-miconazole-and-clotrimazole-in-vitro-effect-on-the-liver-fluke-opisthorchis-felineus
#11
Viatcheslav A Mordvinov, Alexander G Shilov, Maria Y Pakharukova
Discovery of drugs for the treatment of opisthorchiasis and schistosomiasis is a high priority. The basic metabolic cytochrome P450 (CYP) system in parasitic flatworms contains a single gene. CYP of the liver fluke Opisthorchis felineus, the causative agent of opisthorchiasis, is important for survival of the worm, so may be a promising target for therapeutics against liver fluke infection. The aims of this study were: (i) to analyse in-vitro anthelmintic activity of various CYP inhibitors using standard motility and mortality assays against juvenile and adult O...
May 17, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28527613/no-344-opportunistic-salpingectomy-and-other-methods-of-risk-reduction-for-ovarian-fallopian-tube-peritoneal-cancer-in-the-general-population
#12
Shannon Salvador, Stephanie Scott, Julie Ann Francis, Anita Agrawal, Christopher Giede
OBJECTIVE: This guideline reviews the potential benefits of opportunistic salpingectomy to prevent the development of high grade serous cancers (HGSC) of the ovary/fallopian tube/peritoneum based on current evidence supporting the fallopian tube origin of disease. INTENDED USERS: Gynaecologists, obstetricians, family doctors, registered nurses, nurse practitioners, residents, and health care providers. TARGET POPULATION: Adult women (18 and older): OPTIONS: Women considering hysterectomy who wish to retain their ovaries in situ have traditionally also retained their fallopian tubes...
June 2017: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
https://www.readbyqxmd.com/read/28527421/a-phase-iii-randomized-multi-center-double-blind-placebo-controlled-study-of-safety-and-efficacy-of-lofexidine-for-relief-of-symptoms-in-individuals-undergoing-inpatient-opioid-withdrawal
#13
Charles W Gorodetzky, Sharon L Walsh, Peter R Martin, Andrew J Saxon, Kristen L Gullo, Kousick Biswas
BACKGROUND: Lofexidine is an alpha-2-adrenergic receptor agonist approved in the United Kingdom (UK) for the treatment of opioid withdrawal symptoms. Lofexidine has demonstrated better efficacy than placebo for reducing opioid withdrawal symptoms in patients undergoing opioid withdrawal with less reported hypotension than clonidine. METHODS: Designed as an FDA registration trial, this 8-day, randomized, double-blind, placebo-controlled, parallel-group study in 264 patients dependent on short-acting opioids evaluated the efficacy of lofexidine hydrochloride in reducing withdrawal symptoms in patients undergoing opioid withdrawal...
May 10, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28527407/mechanisms-of-resistance-to-systemic-therapy-in-metastatic-castration-resistant-prostate-cancer
#14
REVIEW
Giuseppe Galletti, Benjamin I Leach, Linda Lam, Scott T Tagawa
Patients with metastatic castration-resistant prostate cancer (mCPRC) now have an unprecedented number of approved treatment options, including chemotherapies (docetaxel, cabazitaxel), androgen receptor (AR)-targeted therapies (enzalutamide, abiraterone), a radioisotope (radium-223) and a cancer vaccine (sipuleucel-T). However, the optimal treatment sequencing pathway is unknown, and this problem is exacerbated by the issues of primary and acquired resistance. This review focuses on mechanisms of resistance to AR-targeted therapies and taxane-based chemotherapy...
May 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28527341/unravelling-respiratory-syncytial-virus-outbreaks-in-buenos-aires-argentina-molecular-basis-of-the-spatio-temporal-transmission
#15
Gabriel Lihue Rojo, Stephanie Goya, Mariana Orellana, Andrea Sancilio, Alberto Rodriguez Perez, César Montali, Carolina García, Lilian Sosa, Alejandra Musto, Daniela Alvarez, Alejandro Castello, Mariana Viegas
Respiratory syncytial virus (RSV) is the main viral cause of hospitalization due to acute lower respiratory tract infections in infants worldwide. Several vaccines against RSV are under research and development, which are about to be approved. We evaluated transmission patterns in different settings to determine age-specific vaccination targets from a viral perspective. We sequenced the G glycoprotein's ectodomain of a constant clinical sampling between two epidemic outbreaks in a limited geographical region and performed phylogeographic analyses...
May 17, 2017: Virology
https://www.readbyqxmd.com/read/28527325/dyslipidemia-management-update
#16
REVIEW
Yingzi Chang, Jacques Robidoux
Association of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) is well established. Reducing low-density lipoprotein-cholesterol (LDL-C) and raising high-density lipoprotein-cholesterol (HDL-C) have been the therapeutic targets to reduce the risk of ASCVD. Cholesterol-lowering medications have been used to provide both primary and secondary prevention of ASCVD for many years by reducing the absorption and reabsorption, promoting excretion, or decreasing the synthesis of cholesterol. Within the past five years, several new classes of cholesterol-lowering drugs have been tested and approved for patients with hypercholesterolemia that are not well controlled by conventional therapy (ezetimibe, bile-acid sequestrants, and statins)...
May 17, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28527303/insulin-therapy-in-neonatal-diabetes-mellitus-a-review-of-the-literature
#17
REVIEW
Ivana Rabbone, Fabrizio Barbetti, Raffaella Gentilella, Gilberto Mossetto, Riccardo Bonfanti, Claudio Maffeis, Dario Iafusco, Elvira Piccinno
AIMS: Neonatal diabetes mellitus (NDM) is a rare disorder, and guidance is limited regarding its optimal management. We reviewed insulin usage in NDM, with a focus on continuous subcutaneous insulin infusion (CSII). METHODS: A PubMed search identified 40 reports of patients with NDM treated with insulin published between 1994 and 2016. RESULTS: Data concerning treatment of NDM are limited. CSII resolves some of the issues associated with insulin therapy in neonates...
April 13, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28527254/-cross-cultural-adaptation-of-the-community-acquired-pneumonia-score-questionnaire-in-patients-with-mild-to-moderate-pneumonia-in-colombia
#18
Mónica Alejandra Bernal-Vargas, Jorge Alberto Cortés, Ricardo Sánchez
INTRODUCTION: One of the strategies for the rational use of antibiotics is the use of the score for community-acquired pneumonia (CAP Score). This instrument clinically evaluates patients with community-acquired pneumonia, thereby facilitating decision making regarding the early and safe withdrawal of antibiotics. OBJECTIVE: To generate a translation and cross-cultural adaptation of the Community-Acquired Pneumonia (CAP) Score questionnaire in Spanish. MATERIALS AND METHODS: Authorization for cross-cultural adaptation of the Community-Acquired Pneumonia (CAP) Score questionnaire was obtained; the recommendations of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) and the European Organisation for Research and Treatment of Cancer (EORTC) were carried out through the following stages: forward translation, reconciliation, backward translation, harmonization, obtaining a provisional questionnaire, and applying the questionnaire in a pilot test...
January 24, 2017: Biomédica: Revista del Instituto Nacional de Salud
https://www.readbyqxmd.com/read/28527166/consensus-on-initiation-and-intensification-of-premix-insulin-in-type-2-diabetes-management
#19
Viswanathan Mohan, Sanjay Kalra, Jothydev Kesavadev, Awadhesh Kumar Singh, Ajay Kumar, Ambika Gopalakrishnan Unnikrishnan, Rajeev Chawla, Jagat Jyoti Mukherjee, Rakesh Kumar Sahay, J S Kumar, Anil Bhoraskar, Arthur J Asirvatham, Jayanta Kumar Panda, Abdul Hamid Zargar, Ashok Kumar Das
INTRODUCTION: Premix insulin is the most commonly used insulin preparation in India. The first Indian premix guidelines were developed in 2009 and thereafter were updated in 2013. There is a need to revisit the Indian premix insulin guidelines, in view of emerging evidence and introduction of newer co-formulations. OBJECTIVE: The present consensus has been developed to evaluate available premix formulations, examine existing evidence related to premix formulations, and evolve consensus statement of recommendations on the topic...
April 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28527008/the-role-of-bevacizumab-in-the-treatment-of-glioblastoma
#20
REVIEW
Roberto Jose Diaz, Sheikh Ali, Mehreen Gull Qadir, Macarena I De La Fuente, Michael E Ivan, Ricardo J Komotar
Bevacizumab has been used in patients with GBM as a salvage therapy since its approval in the United States for recurrent GBM in 2009. In order to review the therapeutic effect of bevacizumab in the primary and recurrent clinical setting we have performed a systematic analysis of data from the published literature. Weighted median progression free survival and overall survival were calculated and compared to standard therapy or other experimental therapies. A qualitative analysis of the limited studies on health related quality of life and effects on steroid requirements was also undertaken...
May 19, 2017: Journal of Neuro-oncology
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