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https://www.readbyqxmd.com/read/28216150/novel-biodegradable-poly-gamma-glutamic-acid-amphotericin-b-complexes-show-promise-as-improved-amphotericin-b-formulations
#1
T Dinh, Q Zia, S Zubair, P Stapleton, R Singh, M Owais, S Somavarapu
Commercially available amphotericin B (AmB) formulations are limited either by cytotoxicities, lower efficacies, shelf-life related issues or high production costs. AmB complexes based on poly(gamma-glutamic acid) (PGGA) have been prepared and evaluated for their efficacies against AmB-deoxycholate (Fungizone®) and liposomal AmB (AmBisome®). Physical characterizations showed that AmB/PGGA complexes are nanoscopic (20-40nm) with a negative zetapotential (-51.0mV), water-soluble, stable in solution (up to 4weeks, at 4 °C and 25 °C), and have a theoretical drug loading (up to 76...
February 16, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28216098/potential-influences-of-complement-factor-h-in-autoimmune-inflammatory-and-thrombotic-disorders
#2
Janez Ferluga, Lubna Kouser, Valarmathy Murugaiah, Robert B Sim, Uday Kishore
Complement system homeostasis is important for host self-protection and anti-microbial immune surveillance, and recent research indicates roles in tissue development and remodelling. Complement also appears to have several points of interaction with the blood coagulation system. Deficiency and altered function due to gene mutations and polymorphisms in complement effectors and regulators, including Factor H, have been associated with familial and sporadic autoimmune inflammatory - thrombotic disorders, in which autoantibodies play a part...
February 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28203175/ibrutinib-is-effective-in-the-treatment-of-autoimmune-haemolytic-anaemia-in-mantle-cell-lymphoma
#3
Aliénor Galinier, Vincent Delwail, Mathieu Puyade
Autoimmune haemolytic anaemia (AIHA) in mantle cell lymphoma (MCL) is a rare but life-threatening complication. To date, there are no relevant data for treatment of AIHA in MCL. Ibrutinib, which has been approved for relapse/refractory MCL, is an immunomodulatory drug inhibiting Th2 activation and consequently the production of autoantibodies. We report a case of MCL with AIHA in which this form of anaemia was not controlled with the usual chemotherapy. Ibrutinib was used when MCL with AIHA relapsed, and it allowed rapid remission of AIHA and rapid discontinuation of steroid therapy...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28198349/impact-of-itpa-gene-polymorphisms-on-the-risk-of-ribavirin-induced-haemolytic-anaemia-using-interferon-free-antivirals-for-chronic-hepatitis-c
#4
Isabella Esposito, Laura Benítez-Gutiérrez, Ana Treviño, Ana Arias, Maria Jesus Citores, Silvia Requena, Vicente Soriano, Valentín Cuervas-Mons, Carmen de Mendoza
BACKGROUND: Single nucleotide polymorphisms (SNPs) at the ITPA gene are associated with hemolytic anemia in chronic hepatitis C patients treated with peginterferon-ribavirin (RBV). Information in patients treated with interferon-free, direct-acting antivirals (DAA) is scarce. METHODS: Median hemoglobin (Hb) levels were compared at baseline and at week 4, when ribavirin concentration achieves steady state, in all consecutive chronic hepatitis C patients treated with oral DAA plus RBV at our clinic...
February 15, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28186111/stability-structural-and-functional-properties-of-a-monomeric-calcium-loaded-adenylate-cyclase-toxin-cyaa-from-bordetella-pertussis
#5
Sara E Cannella, Véronique Yvette Ntsogo Enguéné, Marilyne Davi, Christian Malosse, Ana Cristina Sotomayor Pérez, Julia Chamot-Rooke, Patrice Vachette, Dominique Durand, Daniel Ladant, Alexandre Chenal
Bordetella pertussis, the causative agent of whooping cough, secretes an adenylate cyclase toxin, CyaA, which invades eukaryotic cells and alters their physiology by cAMP overproduction. Calcium is an essential cofactor of CyaA, as it is the case for most members of the Repeat-in-ToXins (RTX) family. We show that the calcium-bound, monomeric form of CyaA, hCyaAm, conserves its permeabilization and haemolytic activities, even in a fully calcium-free environment. In contrast, hCyaAm requires sub-millimolar calcium in solution for cell invasion, indicating that free calcium in solution is involved in the CyaA toxin translocation process...
February 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28176831/association-between-cytokine-response-the-lrinec-score-and-outcome-in-patients-with-necrotising-soft-tissue-infection-a-multicentre-prospective-study
#6
Marco Bo Hansen, Lars Simon Rasmussen, Mattias Svensson, Bhavya Chakrakodi, Trond Bruun, Martin Bruun Madsen, Anders Perner, Peter Garred, Ole Hyldegaard, Anna Norrby-Teglund
Early assessment of necrotising soft tissue infection (NSTI) is challenging. Analysis of inflammatory markers could provide important information about disease severity and guide decision making. For this purpose, we investigated the association between cytokine levels and the Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC)-score, disease severity and mortality in NSTI patients. In 159 patients, plasma was analysed for IL-1β, IL-6, IL-10 and TNF-α upon admission. The severity of NSTI was assessed by SAPS, SOFA score, septic shock, microbial aetiology, renal replacement therapy and amputation...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28176479/long-term-remission-with-eculizumab-in-atypical-haemolytic-uraemic-syndrome
#7
REVIEW
Simon Carter, Ian Hewitt, Joshua Kausman
The understanding of the role of complement dysregulation in atypical haemolytic uraemic syndrome (aHUS) has led to major changes in therapeutic approaches and outcomes. Eculizumab is a humanized anti-C5 monoclonal antibody that inhibits the terminal complement pathway and has revolutionized the treatment and prognosis of aHUS. However, published reports to date have had relatively short-term follow-up. We report two paediatric cases of aHUS successfully treated with eculizumab longer than 6 years with no serious adverse events and preservation of renal function...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28176477/absence-of-thrombocytopaenia-and-or-microangiopathic-haemolytic-anaemia-does-not-reliably-exclude-recurrence-of-atypical-haemolytic-uraemic-syndrome-after-kidney-transplantation
#8
REVIEW
Anoushka R Krishnan, Brian Siva, Aron Chakera, Germaine Wong, Daniel Wong, Wai H Lim
A 54-year-old man was diagnosed with atypical haemolytic uraemic syndrome (aHUS) with confirmed complement H mutation in 2012, requiring ongoing dialysis. He was commenced on eculizumab in 2014 once the pharmaceutical board approved this drug. After 4 months, he received a live unrelated donor renal transplant from his wife and continued eculizumab post-transplant. Three months later, there was a rise in his creatinine with no laboratory features of haemolysis and a kidney biopsy confirmed rejection, which was treated with increased immunosuppression...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28176476/recurrent-atypical-haemolytic-uraemic-syndrome-post-kidney-transplant-due-to-a-cd46-mutation-in-the-setting-of-smarcal1-mediated-inherited-kidney-disease
#9
REVIEW
Samuel Chan, Andrew J Mallett, Chirag Patel, Ross S Francis, David W Johnson, David W Mudge, Nicole M Isbel
Disorders in the regulation of the alternate complement pathway often result in complement-mediated damage to the microvascular endothelium and can be associated with both glomerulonephritis and atypical haemolytic uraemic syndrome. Inherited defects in complement regulatory genes or autoantibodies against complement regulatory proteins are predictive of the severity of the disease and the risk of recurrence post kidney transplantation. Heterozygous mutations in CD46, which codes for a transmembrane cofactor glycoprotein membrane cofactor protein, usually have a lower incidence of end-stage kidney disease and decreased risk of recurrent disease post transplant, as wild-type membrane cofactor protein is present in the transplanted kidney...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28176475/life-threatening-pregnancy-associated-atypical-haemolytic-uraemic-syndrome-and-its-response-to-eculizumab
#10
REVIEW
Ryan Gately, Aye San, Jagadeesh Kurtkoti, Alan Parnham
Pregnancy-associated atypical haemolytic uraemic syndrome (P-aHUS) is a rare, potentially lethal condition that can complicate pregnancy in up to 1 in 25 000 cases. Without prompt diagnosis and initiation of appropriate treatment, this condition can lead to disastrous consequences for both mother and child. Given the broad spectrum of conditions that can present similarly in the peripartum period, it is often difficult to establish the correct diagnosis in a timely manner. Recently, the terminal complement cascade inhibitor eculizumab has been used with considerable success in non-pregnancy HUS; however, its use in P-aHUS is limited to isolated case reports...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28176474/monoclonal-gammopathy-of-renal-significance-triggering-atypical-haemolytic-uraemic-syndrome
#11
REVIEW
Usman Mahmood, Nicole Isbel, Peter Mollee, Andrew Mallett, Sridevi Govindarajulu, Ross Francis
Haemolytic uraemic syndrome is a rare condition with an overall incidence of one to two cases in a population of 100 000 and approximately 10% of these cases are classified as atypical. Atypical haemolytic uraemic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by microangiopathic haemolytic anaemia (MAHA), thrombocytopenia and acute kidney injury. aHUS can be genetic, acquired or idiopathic (negative genetic screening and no environmental triggers). We describe a case of aHUS triggered by monoclonal gammopathy of renal significance (MGRS) successfully treated with plasmapheresis and a bortezomib-based chemotherapy regimen, resulting in marked improvement in renal function and other markers of haemolysis...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28176472/suspected-atypical-haemolytic-uraemic-syndrome-in-two-post-partum-patients-with-foetal-death-in-utero-responding-to-eculizumab
#12
REVIEW
Justin Chua, Kathy Paizis, Simon Z He, Peter Mount
BACKGROUND: Atypical haemolytic uraemic syndrome (aHUS) is a rare condition with the triad of microangiopathic haemolytic anaemia, thrombocytopenia and acute kidney injury. Other conditions that present in a similar manner peri-partum include thrombotic thrombocytopaenic purpura, and pregnancy associated conditions including HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), severe pre-eclampsia and less commonly acute fatty liver of pregnancy. CASE REPORTS: We describe two cases of suspected aHUS, who presented post-partum with foetal death-in-utero at 33 and 37 weeks respectively...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28176471/subclinical-atypical-haemolytic-uremic-syndrome-relapse-following-discontinuation-of-eculizumab
#13
REVIEW
Shi Zhou Choo, Fiona Brown
A 25-year-old man presented with microangiopathic haemolytic anaemia and acute kidney injury. With a normal ADAMTS-13 level, negative faecal shiga-toxin test and strong family history of atypical haemolytic uremic syndrome, he was commenced on eculizumab to good clinical response. Subsequent genetic testing revealed a heterozygous complement factor H mutation. Eculizumab was discontinued after 44 months of treatment, and he relapsed within 6 months, with the first sign being downtrending haptoglobin levels, with no other markers of haemolysis or thrombocytopaenia, 5 weeks prior to development of acute kidney injury...
February 2017: Nephrology
https://www.readbyqxmd.com/read/28176163/retrospective-analysis-of-55-twin-neonates-with-haemolytic-disease-of-the-newborn
#14
Hu Zhao, Bijuan Li, Ning Li, Yamei Shen, Kailiang Liu, Xiangwu Shu, Cheng Mei, Lanlan Tang
Haemolytic disease is a condition characterized by anaemia and jaundice, and the course may be more complicated in twins. We investigated the demographic and laboratory characteristics of twins with haemolytic disease of the newborn (HDN) and compared these characteristics between groups categorized according to multiple birth status (twins vs. singletons) and conception method (assisted reproductive technology (ART) vs. spontaneous conception). Fifty-five twins with HDN and 253 singletons with HDN who were born during the same period (controls) were included in the study, and we performed comparisons between them...
February 8, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28170391/haemolysis-in-g6pd-heterozygous-females-treated-with-primaquine-for-plasmodium-vivax-malaria-a-nested-cohort-in-a-trial-of-radical-curative-regimens
#15
Cindy S Chu, Germana Bancone, Kerryn A Moore, Htun Htun Win, Niramon Thitipanawan, Christina Po, Nongnud Chowwiwat, Rattanaporn Raksapraidee, Pornpimon Wilairisak, Aung Pyae Phyo, Lily Keereecharoen, Stéphane Proux, Prakaykaew Charunwatthana, François Nosten, Nicholas J White
BACKGROUND: Radical cure of Plasmodium vivax malaria with 8-aminoquinolines (primaquine or tafenoquine) is complicated by haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD heterozygous females, because of individual variation in the pattern of X-chromosome inactivation (Lyonisation) in erythroid cells, may have low G6PD activity in the majority of their erythrocytes, yet are usually reported as G6PD "normal" by current phenotypic screening tests...
February 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28165051/insights-into-structure-and-activity-of-natural-compound-inhibitors-of-pneumolysin
#16
Hongen Li, Xiaoran Zhao, Xuming Deng, Jianfeng Wang, Meng Song, Xiaodi Niu, Liping Peng
Pneumolysin is the one of the major virulence factor of the bacterium Streptococcus pneumoniae. In previous report, it is shown that β-sitosterol, a natural compound without antimicrobial activity, is a potent antagonist of pneumolysin. Here, two new pneumolysin natural compound inhibitors, with differential activity, were discovered via haemolysis assay. To explore the key factor of the conformation for the inhibition activity, the interactions between five natural compound inhibitors with differential activity and pneumolysin were reported using molecular modelling, the potential of mean force profiles...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28162051/henoch-schonlein-purpura-post-streptococcal-glomerulonephritis-and-acute-rheumatic-carditis-after-group-a-%C3%AE-haemolytic-streptococcal-infection
#17
Seçil Arslansoyu Çamlar, Alper Soylu, İpek Akil, Mehtat Ünlü, Şenol Coşkun, Pelin Ertan, Salih Kavukçu
Besides association with acute rheumatic fever (ARF) and acute glomerulonephritis (APSGN), in up to 40% of cases, Group A β-haemolytic streptococcal (GABHS) infections are also implicated as a trigger for Henoch-Schonlein purpura (HSP). A 7-year-old girl with GABHS throat infection who developed HSP, APSGN and rheumatic carditis is reported. She presented with palpable purpura and arthritis in both ankles and later developed carditis characterised by mitral/aortic regurgitation and glomerulonephritis characterised by mixed nephritic/nephrotic syndrome...
February 6, 2017: Paediatrics and International Child Health
https://www.readbyqxmd.com/read/28159390/sickle-cell-disease
#18
REVIEW
Russell E Ware, Mariane de Montalembert, Léon Tshilolo, Miguel R Abboud
Sickle cell disease is a common and life-threatening haematological disorder that affects millions of people worldwide. Abnormal sickle-shaped erythrocytes disrupt blood flow in small vessels, and this vaso-occlusion leads to distal tissue ischaemia and inflammation, with symptoms defining the acute painful sickle-cell crisis. Repeated sickling and ongoing haemolytic anaemia, even when subclinical, lead to parenchymal injury and chronic organ damage, causing substantial morbidity and early mortality. Currently available treatments are limited to transfusions and hydroxycarbamide, although stem cell transplantation might be a potentially curative therapy...
January 31, 2017: Lancet
https://www.readbyqxmd.com/read/28157719/preclinical-safety-and-efficacy-evaluation-of-biocas-bioactive-calcium-sulfate-bone-cement
#19
Sony Sandhya, Parayanthala Valappil Mohanan, Arumugan Sabareeswaran, Hari Krishna Varma, Manoj Komath
A new bioactive calcium sulfate-based formulation (named 'BioCaS') has been developed for bone filler applications. This is a self-setting injectable cement where the preset form comprises bassanite obtained from the uniform submicron-sized precursor crystals of gypsum, modified with hydrogen orthophosphate ions. The results of the safety and efficacy evaluation of BioCaS cement, done as per the International Standards and guidelines, are presented in this paper. The study plan consisted of in vitro screening tests of cytotoxicity and haemolysis and in vivo biocompatibility evaluation, including an acute systemic toxicity test (in mice), an intracutaneous reactivity test (in rabbits), a pyrogen test (in rabbits) and a maximization sensitization test (in guinea pigs)...
February 3, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28155819/modelling-primaquine-induced-haemolysis-in-g6pd-deficiency
#20
James Watson, Walter Rj Taylor, Didier Menard, Sim Kheng, Nicholas J White
Primaquine is the only drug available to prevent relapse in vivax malaria. The main adverse effect of primaquine is erythrocyte age and dose dependent acute haemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd). As testing for G6PDd is often unavailable this limits the use of primaquine for radical cure. A compartmental model of the dynamics of red blood cell production and destruction was designed to characterise primaquine-induced haemolysis using a holistic Bayesian analysis of all published data and was used to predict a safer alternative to the currently recommended once weekly 0...
February 3, 2017: ELife
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