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https://www.readbyqxmd.com/read/29782330/a-transgenic-mouse-model-for-hla-b-57-01-linked-abacavir-drug-tolerance-and-reactivity
#1
Marco Cardone, Karla Garcia, Mulualem E Tilahun, Lisa F Boyd, Sintayehu Gebreyohannes, Masahide Yano, Gregory Roderiquez, Adovi D Akue, Leslie Juengst, Elliot Mattson, Suryatheja Ananthula, Kannan Natarajan, Montserrat Puig, David H Margulies, Michael A Norcross
Adverse drug reactions (ADRs) are a major obstacle to drug development, and some of these, including hypersensitivity reactions to the HIV reverse transcriptase inhibitor abacavir (ABC), are associated with HLA alleles, particularly HLA-B*57:01. However, not all HLA-B*57:01+ patients develop ADRs, suggesting that in addition to the HLA genetic risk, other factors may influence the outcome of the response to the drug. To study HLA-linked ADRs in vivo, we generated HLA-B*57:01-Tg mice and show that, although ABC activated Tg mouse CD8+ T cells in vitro in a HLA-B*57:01-dependent manner, the drug was tolerated in vivo...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29782303/clindamycin-induced-maculopapular-exanthema-with-preferential-involvement-of-striae-distensae-a-koebner-phenomenon
#2
Benigno Monteagudo, Miguel Cabanillas, Pilar Iriarte, Aquilina Ramírez-Santos, Elvira León-Muinos, Daniel González-Vilas, Óscar Suárez-Amor
Clindamycin is a lincomycin-derived antibiotic useful for the treatment of anaerobic and Gram-positive aerobic bacterial infections. Cutaneous adverse reactions are usually maculopapular exanthemas, although hypersensitivity syndrome, acute generalized exanthematous pustulosis, and Stevens-Johnson syndrome have also been reported (1). We report the case of a patient with a maculopapular rash triggered by clindamycin who developed cutaneous lesions on striae distensae (SD). A 47-year-old woman was referred to our clinic for pruritic cutaneous lesions which had started 6 days earlier...
April 2018: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/29781810/active-suppression-rather-than-ignorance-tolerance-to-abacavir-induced-hla-b-57-01-peptide-repertoire-alteration
#3
Elizabeth J Phillips, Simon A Mallal
The discovery of HLA-B*57:01-associated abacavir hypersensitivity is a translational success story that eliminated adverse reactions to abacavir through pretreatment screening and defined a mechanistic model of an altered peptide repertoire. In this issue of the JCI, Cardone et al. have developed an HLA-B*57:01-transgenic mouse model and demonstrated that CD4+ T cells play a key role in mediating tolerance to the dramatically altered endogenous peptide repertoire induced by abacavir and postulate a known mechanism by which CD4+ T cells suppress DC maturation...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29780064/systemic-lupus-erythematosus-and-sj%C3%A3-gren-s-syndrome-complicated-by-conversion-disorder-a-case-report
#4
Misa Nakamura, Seiji Tanaka, Tadashi Inoue, Yasuto Maeda, Kiyohito Okumiya, Takuya Esaki, G O Shimomura, Kenji Masunaga, Shinichiro Nagamitsu, Yushiro Yamashita
Conversion disorder (CD) is sometimes accompanied by motor and sensory impairments, such as muscle weakness, paralysis, sensory hypersensitivity, and sensory loss. Sjögren's syndrome (SS) complicates 5-10% of cases of systemic lupus erythematosus (SLE). Patients with SS or SLE present with various neurological symptoms and psychiatric manifestations. When neurological symptoms are present, it is important to distinguish whether the symptoms are caused by a neurological or a mental disorder because the former requires early intensive intervention, such as methylprednisolone pulse therapy (MPT), whereas psychotherapy or antidepressant drugs are recommended for mental disorders...
May 21, 2018: Kurume Medical Journal
https://www.readbyqxmd.com/read/29769286/targeted-inhibition-of-histone-h3k27-demethylation-is-effective-in-high-risk-neuroblastoma
#5
Timothy L Lochmann, Krista M Powell, Jungoh Ham, Konstantinos V Floros, Daniel A R Heisey, Richard I J Kurupi, Marissa L Calbert, Maninderjit S Ghotra, Patricia Greninger, Mikhail Dozmorov, Madhu Gowda, Andrew J Souers, C Patrick Reynolds, Cyril H Benes, Anthony C Faber
High-risk neuroblastoma is often distinguished by amplification of MYCN and loss of differentiation potential. We performed high-throughput drug screening of epigenetic-targeted therapies across a large and diverse tumor cell line panel and uncovered the hypersensitivity of neuroblastoma cells to GSK-J4, a small-molecule dual inhibitor of lysine 27 of histone 3 (H3K27) demethylases ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), and histone demethylase Jumonji D3 (JMJD3). Mechanistically, GSK-J4 induced neuroblastoma differentiation and endoplasmic reticulum (ER) stress, with accompanying up-regulation of p53 up-regulated modulator of apoptosis (PUMA) and induction of cell death...
May 16, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29766368/systemic-contact-dermatitis
#6
REVIEW
Marcella Aquino, Greg Rosner
Systemic contact dermatitis (SCD) traditionally refers to a skin condition where an individual who is cutaneously sensitized to an allergen will subsequently react to that same allergen or a cross reacting allergen via a different route. It occurs to allergens including metals, medications, and foods. The exact pathophysiology underlying this disease remains unknown, although it appears to be mediated by type 4 hypersensitivity reactions and possibly type 3 hypersensitivity reactions. The p-I concept (pharmacologic interaction with immunoreceptors) hypothesized that drugs are able to bind directly to a T cell receptor without first being presented by MHC (major histocompatibility complex) molecules and without prior metabolism, which would help explain why SCD can be seen on first exposure to medications...
May 15, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29765441/suspected-unexpected-and-other-adverse-reactions-to-antiretroviral-drugs-used-as-post-exposure-prophylaxis-of-hiv-infection-five-year-experience-from-clinical-practice
#7
Justyna D Kowalska, Ewa Pietraszkiewicz, Ewa Firląg-Burkacka, Andrzej Horban
Introduction: With increased use of antiretroviral drugs (ARVs) in HIV uninfected persons, proper reporting on suspected unexpected serious adverse reactions (SUSARs) and continued insight into adverse drug reactions (ADRs) are needed for adequate information on safety of ARVs in such populations. Material and methods: Medical documentation of persons receiving ARVs after non-occupational HIV exposure (non-occupational post-exposure prophylaxis - nPEP) during 5 successive years (2009-2013) was evaluated by two HIV physicians...
April 2018: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29765217/allergy-to-chlorpromazine-and-valproic-acid-following-carbamazepine-hypersensitivity-in-a-patient-with-an-hla-b-4601-allele
#8
Kumi Sakurada, Takeshi Kozaru, Kazuo Yamada, Masashi Nibuya, Kiyoshi Nagata, Eiji Suzuki
A 73-year-old man, exhibiting psychomotor excitement after traumatic brain injury, developed allergic cutaneous eruptions and hepatic inflammation that did not resolve after the cessation of carbamazepine (CBZ). Fusing maculopapular erythema was observed in the face, neck, presternal region, and bilaterally in the forearms and feet. A drug-induced lymphocyte stimulation test revealed hypersensitivity to chlorpromazine (CPZ) and valproic acid (VPA), as well as to CBZ. The allergic reaction with eosinophilia to CPZ and VPA was suspected to have emerged following CBZ hypersensitivity, since previous treatment with CPZ and VPA prior to the introduction of CBZ had not been associated with adverse reactions earlier in the course of treatment...
2018: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29760877/an-eaaci-task-force-report-recognising-the-potential-of-the-primary-care-physician-in-the-diagnosis-and-management-of-drug-hypersensitivity
#9
REVIEW
I Doña, J C Caubet, K Brockow, M Doyle, E Moreno, I Terreehorst, M J Torres
Adverse drug reactions include drug hypersensitivity reactions (DHRs), which can be immunologically mediated (allergy) or non-immunologically mediated. The high number of DHRs that are unconfirmed and often self-reported is a frequent problem in daily clinical practice, with considerable impact on future prescription choices and patient health. It is important to distinguish between hypersensitivity and non-hypersensitivity reactions by adopting a structured diagnostic approach to confirm or discard the suspected drug, not only to avoid life-threatening reactions, but also to reduce the frequent over-diagnosis of DHRs...
2018: Clinical and Translational Allergy
https://www.readbyqxmd.com/read/29755982/clinical-genetics-in-interstitial-lung-disease
#10
REVIEW
Chad A Newton, Philip L Molyneaux, Justin M Oldham
Interstitial lung disease (ILD) comprises a heterogeneous group of diffuse parenchymal lung processes with overlapping clinical, radiographic, and histopathologic features. Among the most common and deadly ILDs are idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (CHP). As the name implies, the cause of IPF remains elusive, but a variety of genetic and infectious risk factors have been identified. CHP results from chronic inhalation of an organic antigen, usually of avian or mold origin, and may occur in patients with a genetic predisposition...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29755712/lymphoproliferative-syndromes-associated-with-human-herpesvirus-6a-and-human-herpesvirus-6b
#11
REVIEW
Eva Eliassen, Gerhard Krueger, Mario Luppi, Dharam Ablashi
Human herpesvirus 6A and 6B (HHV-6A and HHV-6B) have been noted since their discovery for their T-lymphotropism. Although it has proven difficult to determine the extent to which HHV-6A and HHV-6B are involved in the pathogenesis of many diseases, evidence suggests that primary infection and reactivation of both viruses may induce or contribute to the progression of several lymphoproliferative disorders, ranging from benign to malignant and including infectious mononucleosis-like illness, drug induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (DIHS/DRESS), and nodular sclerosis Hodgkin's lymphoma...
2018: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/29751529/the-use-and-safety-of-tnf-inhibitors-during-pregnancy-in-women-with-psoriasis-a-review
#12
REVIEW
Cæcilie Bachdal Johansen, Espen Jimenez-Solem, Ann Haerskjold, Freja Lærke Sand, Simon Francis Thomsen
Psoriasis is a chronic immune-mediated inflammatory disease affecting women of childbearing potential. Biologic agents, notably Tumor Necrosis Factor inhibitors (TNFi), are the only current non-contraindicated systemic treatment option during pregnancy. TNFi comprised of complete immunoglobulin G (IgG) antibodies antibodies (adalimumab, golimumab, and infliximab) actively cross the placenta from the second trimester and are detectable in the child up to one year postpartum. Data on safety of TNFi are conflicting; however a trend towards drug-specific harm has been reported, with increased risk of congenital malformations and preterm birth...
May 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29744372/recent-advances-in-drug-induced-hypersensitivity-syndrome-drug-reaction-with-eosinophilia-and-systemic-symptoms
#13
REVIEW
Hideaki Watanabe
Drug-induced hypersensitivity syndrome (DIHS), also termed as drug reaction with eosinophilia and systemic symptoms (DRESS), is a multiorgan systemic reaction characterized by a close relationship with the reactivation of herpes virus. Published data has demonstrated that among patients with DIHS/DRESS, 75-95% have leukocytosis, 18.2-90% show atypical lymphocytes, 52-95% have eosinophilia, and 75-100% have hepatic abnormalities. Histologically, eosinophils were observed less frequently than we expected (20%)...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29742970/stability-of-carboplatin-infusion-solutions-used-in-desensitization-protocol
#14
R Vázquez-Sánchez, J Sánchez-Rubio-Ferrández, D Córdoba-Díaz, M Córdoba-Díaz, T Molina-Garcia
Carboplatin hypersensitivity reactions are one of the major clinical challenges in treating patients with relapse/recurrent ovarian malignancies. Desensitization protocols allow the continuation of treatment in patients who have presented hypersensitivity reactions by gradually re-introducing small amounts of the drug up to full therapeutic doses. Carboplatin desensitization protocol is based on three solutions that are usually prepared in the chemotherapy centralized units of hospital pharmacies. First and second solutions are diluted under the established concentration limit to guarantee the stability of the preparation...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29733431/adverse-drug-reactions-reported-by-healthcare-professionals-reaction-characteristics-and-time-to-reporting
#15
Ar Kar Aung, Mei Jie Tang, Nikki Rae Adler, Sara Lee de Menezes, Michelle Sue Yen Goh, Hui Wen Tee, Jason Anthony Trubiano, Robert Puy, Celia Mary Zubrinich, Linda Velta Graudins
We describe adverse drug reaction (ADR) reporting characteristics and factors contributing to length of time to report by healthcare professionals. This is a retrospective study of voluntary reports to an Australian healthcare ADR Review Committee over a 2-year period (2015-2016). Descriptive and univariate models were used for outcomes, employing standardized ADR definitions. Hospital pharmacists reported 84.8% of the 555 ADRs: 70.3% were hospital onset reactions, and 71.7% were at least of moderate severity...
May 7, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29731949/stevens-johnson-syndrome-and-toxic-epidermal-necrolysis-extensive-review-of-reports-of-drug-induced-etiologies-and-possible-therapeutic-modalities
#16
REVIEW
Adegbenro Omotuyi John Fakoya, Princess Omenyi, Precious Anthony, Favour Anthony, Precious Etti, David Adeiza Otohinoyi, Esther Olunu
Stevens - Johnson Syndrome and Toxic Epidermal Necrolysis are adverse hypersensitivity reactions that affect the skin and mucous membranes. They are characterised by erythematous macules and hemorrhagic erosions of the mucous membranes. Epidermal detachments of varying degrees of severity also occur in these conditions. Various aetiologies are associated with these conditions, with adverse drug reaction being the most common. Though the worldwide incidence of these conditions is recorded as low, diverse types of medication are being observed to lead to these conditions...
April 15, 2018: Open Access Macedonian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29728195/potassium-oxalate-mouthrinse-reduces-dentinal-hypersensitivity-a-randomized-controlled-clinical-study
#17
Michael C Lynch, Roland Perfekt, James A McGuire, Jeffery Milleman, John Gallob, Pejmon Amini, Kimberly Milleman
BACKGROUND: Dentinal hypersensitivity is a prevalent oral condition that can be treated with in-office application of potassium oxalate (KO), which has US Food and Drug Administration 510(k) clearance. In this study, the authors assessed a KO mouthrinse for home use. The authors evaluated clinically meaningful improvement by analyzing the proportions of participants who responded to treatment. METHODS: In this multicenter, double-blind, parallel-group controlled study, the authors randomly assigned 375 participants with dentinal hypersensitivity to 1 of 2 mouthrinse groups: KO (189 participants) and placebo (186 participants)...
May 2, 2018: Journal of the American Dental Association
https://www.readbyqxmd.com/read/29723946/-plantago-psyllium-secondary-anaphylaxis-case-report
#18
Rodrigo Collado-Chagoya, Javier Hernández-Romero, Gumaro Alejandro Eliosa-Alvarado, Ana Carmen García-González, Rosa Isela Campos-Gutiérrez, Andrea Velasco-Medina, Guillermo Velázquez-Sámano
BACKGROUND: Psyllium is a derivative of Plantago ovata ground seed and husk that is used as bulk-forming laxatives owing to its hydrocolloid properties. CASE REPORT: 43-year-old female nurse with previous diagnosis of drug allergy and allergic rhinitis who, after the preparation and administration of a laxative, developed rhinoconjunctivitis symptoms, urticarial syndrome, angioedema and bronchospasm, which led to conclude that she had an anaphylactic reaction. She was treated with adrenaline, corticosteroids and antihistamines...
January 2018: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
https://www.readbyqxmd.com/read/29723945/-are-natural-analgesic-products-safe-in-patients-with-allergy-to-non-steroidal-anti-inflammatory-drugs
#19
Iván Chérrez-Ojeda, Juan Carlos Calderón, Erick Calero, César Terán, Annia Chérrez
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAID)-induced hypersensitivity reactions can be clinically apparent with asthma, rhinosinusitis, anaphylaxis or rash. Although natural anti-inflammatory products can have similar components, they are not subjected to rigorous quality control standards. CASE REPORT: The case is presented of a 22-year-old female with NSAID allergy who attended with facial and laryngeal angioedema associated with pruritus in eyelids and pharynx...
January 2018: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
https://www.readbyqxmd.com/read/29721165/precision-cancer-therapy-profiting-from-tumor-specific-defects-in-the-dna-damage-tolerance-system
#20
Olimpia Alessandra Buoninfante, Bas Pilzecker, Muhammad Assad Aslam, Ioannis Zavrakidis, Rianne van der Wiel, Marieke van de Ven, Paul C M van den Berk, Heinz Jacobs
DNA damage tolerance (DDT) enables replication to continue in the presence of a damaged template and constitutes a key step in DNA interstrand crosslink repair. In this way DDT minimizes replication stress inflicted by a wide range of endogenous and exogenous agents, and provides a critical first line defense against alkylating and platinating chemotherapeutics. Effective DDT strongly depends on damage-induced, site-specific PCNA-ubiquitination at Lysine (K) 164 by the E2/E3 complex (RAD6/18). A survey of The Cancer Genome Atlas (TCGA) revealed a high frequency of tumors presents RAD6/RAD18 bi-allelic inactivating deletions...
April 10, 2018: Oncotarget
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