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https://www.readbyqxmd.com/read/29140831/relative-efficacies-of-hboc-201-and-polyheme-to-increase-oxygen-transport-compared-to-blood-and-crystalloids-2017-military-supplement
#1
Gregory P Dubé, Arkadiy N Pitman, Colin F Mackenzie
BACKGROUND: Because total hemoglobin in circulation ([THb]) is an established predictor of clinical outcomes in anemic individuals, the relative efficacies of resuscitation fluids to increase [THb] can be used to design better hemoglobin-based oxygen carrier (HBOC) clinical trials. METHODS: Expected efficacies of HBOC-201 (13 g Hb/dL) and packed RBCs (pRBCs, 24 g Hb/dL) to increase [THb] were calculated and interpreted in the context of SAEs in the HEM-0115 phase III clinical trial...
November 14, 2017: Shock
https://www.readbyqxmd.com/read/29124494/information-and-support-needs-of-young-women-regarding-breast-cancer-risk-and-genetic-testing-adapting-effective-interventions-for-a-novel-population
#2
Suzanne C O'Neill, Chalanda Evans, Rebekah J Hamilton, Beth N Peshkin, Claudine Isaacs, Sue Friedman, Kenneth P Tercyak
Young women from hereditary breast and ovarian cancer (HBOC) families face a unique set of challenges in managing their HBOC risk, where obtaining essential information to inform decision making is key. Previous work suggests that this need for specific health information also comes at a time of heightened distress and greater individuation from family. In this report, we describe our adaptation of a previously-studied behavioral intervention for this population, utilizing a systematic approach outlined by the Centers for Disease Control and Prevention...
November 9, 2017: Familial Cancer
https://www.readbyqxmd.com/read/29112633/2017-military-supplement-current-challenges-in-the-development-of-acellular-hemoglobin-oxygen-carriers-by-protein-engineering
#3
Andres S Benitez Cardenas, Premila P Samuel, John S Olson
This article reviews the key biochemical mechanisms that govern O2 transport, NO scavenging, and oxidative degradation of acellular hemoglobin and how these ideas have been used to try to develop strategies to engineer safer and more effective hemoglobin-based oxygen carriers (HBOCs). Significant toxicities due to acellular hemoglobin (Hb) have been observed after the administration of HBOCs or after the lysis of red cells, and include: (a) rapid clearance and kidney damage due to dissociation into dimers, haptoglobin binding, and macrophage activation; (b) early O2 release leading to decreased tissue perfusion in capillary beds; (c) interference with endothelial and smooth muscle signaling due to nitric oxide (NO) scavenging; (d) autooxidization of heme iron followed by production of reactive oxygen species; and (e) iron overload symptoms due to hemin loss, globin denaturation, iron accumulation, and further inflammation...
November 6, 2017: Shock
https://www.readbyqxmd.com/read/29112106/mechanisms-of-toxicity-and-modulation-of-hemoglobin-based-oxygen-carriers-hbocs
#4
Abdu I Alayash
Several adverse events have been associated with the infusion of hemoglobin-based oxygen carriers (HBOCs) including transient hypertension, gastrointestinal, pancreatic/liver enzyme elevation, and cardiac/renal injury in humans. Although several mechanisms have been suggested, the basis of HBOC toxicity is still poorly understood. Scavenging of vascular endothelial nitric oxide (NO) and heme-mediated oxidative side reactions are thought to be the major causes of toxicity. However, based on more recent preclinical studies, oxidative pathways (driven by the heme prosthetic group) appear to play a more prominent role in the overall toxicity of free Hb or HBOCs...
November 3, 2017: Shock
https://www.readbyqxmd.com/read/29081252/glutaraldehyde-inactivation-of-enveloped-dna-viruses-in-the-preparation-of-haemoglobin-based-oxygen-carriers
#5
Huiya Ma, Qiuhui Li, Kun Feng, Yuanyuan Zhang, Hongli Zhu, Chao Chen, Kunping Yan
Glutaraldehyde (GA), used medically as a disinfectant and as a crosslinker for haemoglobin (Hb)-based oxygen carriers (HBOCs), was investigated for its ability to inactivate viruses during the preparation of these artificial blood substitutes. Porcine parvovirus (PPV; a non-enveloped DNA virus) and porcine pseudorabies virus (PRV; an enveloped DNA virus) were used as the virus indicators. Upon treatment with 0.1 mM GA, the titer of PRV decreased from 9.62 log10 to 2.62 log10 within 0.5 h, whereas that of PPV decreased from 7...
October 28, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29076972/users-guide-to-pitfalls-and-lessons-learned-about-hboc-201-during-clinical-trials-expanded-access-and-clinical-use-in-1-701-patients
#6
Colin F Mackenzie, Gregory P Dubé, Arkaidy Pitman, Melissa Zafirelis
Lessons learned during 1,701 clinical uses of HBOC-201, a polymerized bovine hemoglobin-based oxygen carrier (HBOC), were identified to provide management lessons and training material for future clinical trials and use. HBOC-201 contains 13 g/dL hemoglobin (Hb), is iso-oncotic, stable at 2°C to 30°C with shelf-life of 3 years, requires no cross-matching with half-life of 19 h, and plasma volume distribution. Adverse effects include increased blood pressure, oliguria, gastrointestinal (GI) symptoms, yellow skin and scleral discoloration, decreased pulse oximetry measurements, and transient increases in methemoglobin, hepatic, and pancreatic enzymes...
October 25, 2017: Shock
https://www.readbyqxmd.com/read/29076161/use-of-the-blood-substitute-hboc-201-in-critically-ill-patients-during-sickle-crisis-a-three-case-series
#7
Jonathan M Davis, Nura El-Haj, Nimish N Shah, Garry Schwartz, Margaret Block, James Wall, Mark Tidswell, Ernest DiNino
BACKGROUND: Red blood cell (RBC) transfusion is an important treatment modality during severe sickle cell crisis (SCC). SCC patients who refuse, or cannot accept, RBCs present a unique challenge. Acellular hemoglobin (Hb)-based oxygen carriers (HBOCs) might be an alternative for critically ill patients in SCC with multiorgan failure due to life-threatening anemia. HBOC-201 (HbO2 Therapeutics) has been administered to more than 800 anemic patients in 22 clinical trials, but use of any HBOCs in critically ill sickle cell patients with organ failure is exceedingly rare...
October 26, 2017: Transfusion
https://www.readbyqxmd.com/read/29054729/hib-antibody-responses-in-infants-following-diphtheria-tetanus-acellular-pertussis-and-conjugated-haemophilus-influenzae-type-b-hib-combination-vaccines-with-decreasing-amounts-of-tetanus-toxoid
#8
Henry H Bernstein, Elisabeth R Seyferth
BACKGROUND: While combination vaccines have contributed to improved vaccine uptake rates in children, studies have documented varied immunogenicity to specific vaccine components. We studied whether varying the amount of tetanus toxoid (TT) in a DTaP and Hib combination vaccine would result in immunogenicity comparable with separate, concurrent administration. METHODS: We evaluated the immunogenicity of Massachusetts Biologic Laboratories (MBL) diphtheria, tetanus, and acellular pertussis (mDTaP) vaccine combined with tetanus-conjugated MBL Haemophilus influenzae type b vaccine (mHib) in a single injection (DTaPH)...
October 17, 2017: Vaccine
https://www.readbyqxmd.com/read/29021619/pan-cancer-analysis-of-bi-allelic-alterations-in-homologous-recombination-dna-repair-genes
#9
Nadeem Riaz, Pedro Blecua, Raymond S Lim, Ronglai Shen, Daniel S Higginson, Nils Weinhold, Larry Norton, Britta Weigelt, Simon N Powell, Jorge S Reis-Filho
BRCA1 and BRCA2 are involved in homologous recombination (HR) DNA repair and are germ-line cancer pre-disposition genes that result in a syndrome of hereditary breast and ovarian cancer (HBOC). Whether germ-line or somatic alterations in these genes or other members of the HR pathway and if mono- or bi-allelic alterations of HR-related genes have a phenotypic impact on other cancers remains to be fully elucidated. Here, we perform a pan-cancer analysis of The Cancer Genome Atlas (TCGA) data set and observe that bi-allelic pathogenic alterations in homologous recombination (HR) DNA repair-related genes are prevalent across many malignancies...
October 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/29020660/identification-of-twenty-nine-novel-germline-unclassified-variants-of-brca1-and-brca2-genes-in-1400-italian-individuals
#10
Concetta Santonocito, Margherita Scapaticci, Donatella Guarino, Andrea Bartolini, Angelo Minucci, Paola Concolino, Giovanni Scambia, Ida Paris, Ettore Capoluongo
OBJECTIVES: Breast and/or ovarian cancers are complex multifactorial diseases caused by interaction of both genetic and non-genetic factors and characterized by predisposition to inheritance. BRCA1 and BRCA2 genes are the most clinically involved with these kinds of cancer and the spectrum of variants affecting these genes is very wide. In fact, point variants, large or small insertions/deletions, genomic rearrangements can be found in these patients, although a large number of variants with uncertain biological and clinical significance continues to be identified...
December 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28993866/cdh1-mutation-screen-in-a-brca1-2-negative-familial-breast-ovarian-cancer-cohort
#11
Frederik Stuebs, Simone Heidemann, Almuth Caliebe, Christoph Mundhenke, Norbert Arnold
PURPOSE: Mutations in the CDH1 gene are linked both to diffuse gastric cancer and invasive lobular carcinoma (ILC). A high mutation rate is found in families fulfilling the diagnostic criteria for hereditary diffuse gastric cancer. Aim of this study was to clarify whether or not there is a significant contribution of CDH1 mutations in hereditary breast-/ovarian cancer (HBOC). METHODS: Ninety-seven unrelated probands fulfilling the diagnostic criteria for HBOC (96 affected, 1 unaffected) but tested negative for pathogenic BRCA1/2 mutations were screened for CDH1 mutations by denaturing high performance liquid chromatography (DHPLC) and subsequent Sanger sequencing of suspicious and positive DHPLC results...
October 9, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28986211/in-vivo-evaluation-of-hemerythrin-based-oxygen-carriers-similarities-with-hemoglobin-based-counterparts
#12
Vlad Al Toma, Anca D Farcas, Ioana Roman, Bogdan Sevastre, Denisa Hathazi, Florina Scurtu, Grigore Damian, Radu Silaghi-Dumitrescu
We have previously proposed the annelid-derived protein, hemerythrin, as a viable replacement for hemoglobin in the synthesis of semi-synthetic oxygen carriers ("blood substitutes"). Here, we report the first in vivo tests for potential hemerythrin-based oxygen carriers (HrBOC), using a battery of experiments involving Wistar rats and previously tested on a series of hemoglobin-based oxygen carrier candidates (HBOC). At the concentrations tested, hemerythrin appears to behave similarly to hemoglobin - including, importantly, immunological effects...
October 3, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28968286/2017-military-supplement-hemoglobin-based-oxygen-carriers-current-state-of-the-art-and-novel-molecules
#13
Anirban Sen Gupta
In blood, the primary role of RBCs is to transport oxygen via highly regulated mechanisms involving hemoglobin (Hb). Hb is a tetrameric porphyrin protein comprising of two α- and two β-polypeptide chains, each containing an iron-containing heme group capable of binding one oxygen molecule. In military as well as civilian traumatic exsanguinating hemorrhage, rapid loss of RBCs can lead to sub-optimal tissue oxygenation and subsequent morbidity and mortality. In such cases, transfusion of whole blood or RBCs can significantly improve survival...
September 29, 2017: Shock
https://www.readbyqxmd.com/read/28961279/the-frequency-of-cancer-predisposition-gene-mutations-in-hereditary-breast-and-ovarian-cancer-patients-in-taiwan-from-brca1-2-to-multi-gene-panels
#14
Pi-Lin Sung, Kuo-Chang Wen, Yi-Jen Chen, Ta-Chung Chao, Yi-Fang Tsai, Ling-Ming Tseng, Jian-Tai Timothy Qiu, Kuan-Chong Chao, Hua-Hsi Wu, Chi-Mu Chuang, Peng-Hui Wang, Chi-Ying F Huang
An important role of genetic factors in the development of breast cancer (BC) or ovarian cancer (OC) in Taiwanese (ethnic Chinese) patients has been suggested. However, other than germline BRCA1 or BRCA2 mutations, which are related to hereditary breast-ovarian cancer (HBOC), cancer-predisposition genes have not been well studied in this population. The aim of the present study was to more accurately summarize the prevalence of genetic mutations in HBOC patients using various gene panels ranging in size from BRCA1/2 alone to multi-gene panels...
2017: PloS One
https://www.readbyqxmd.com/read/28931501/cancer-predisposition-cascade-screening-for-hereditary-breast-ovarian-cancer-and-lynch-syndromes-in-switzerland-study-protocol
#15
Maria C Katapodi, Valeria Viassolo, Maria Caiata-Zufferey, Christos Nikolaidis, Rosmarie Bührer-Landolt, Nicole Buerki, Rossella Graffeo, Henrik Csaba Horváth, Christian Kurzeder, Manuela Rabaglio, Michael Scharfe, Corinne Urech, Tobias E Erlanger, Nicole Probst-Hensch, Karl Heinimann, Viola Heinzelmann-Schwarz, Olivia Pagani, Pierre O Chappuis
BACKGROUND: Breast, colorectal, ovarian, and endometrial cancers constitute approximately 30% of newly diagnosed cancer cases in Switzerland, affecting more than 12,000 individuals annually. Hundreds of these patients are likely to carry germline pathogenic variants associated with hereditary breast ovarian cancer (HBOC) or Lynch syndrome (LS). Genetic services (counseling and testing) for hereditary susceptibility to cancer can prevent many cancer diagnoses and deaths through early identification and risk management...
September 20, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28930807/breadth-of-genetic-testing-selected-by-patients-at-risk-of-hereditary-breast-and-ovarian-cancer
#16
J Brian Szender, Jasmine Kaur, Katherine Clayback, Mollie L Hutton, June Mikkelson, Kunle Odunsi, Cara Dresbold
OBJECTIVE: The aim of this study was to evaluate the ability of patients at risk of hereditary breast and ovarian cancer (HBOC) syndrome to select the extent of genetic testing personally preferred and the impact of demographic factors on the breadth of testing pursued. METHODS: A single-institution cohort was enumerated consisting of patients referred for clinical genetic counseling secondary to risk of HBOC syndrome. This was a retrospective study of consecutive patients seen for genetic counseling; all patients completed an epidemiologic questionnaire and provided personal and family medical histories...
September 19, 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28905878/detecting-splicing-patterns-in-genes-involved-in-hereditary-breast-and-ovarian-cancer
#17
Grégoire Davy, Antoine Rousselin, Nicolas Goardon, Laurent Castéra, Valentin Harter, Angelina Legros, Etienne Muller, Robin Fouillet, Baptiste Brault, Anna S Smirnova, Fréderic Lemoine, Pierre de la Grange, Marine Guillaud-Bataille, Virginie Caux-Moncoutier, Claude Houdayer, Françoise Bonnet, Cécile Blanc-Fournier, Pascaline Gaildrat, Thierry Frebourg, Alexandra Martins, Dominique Vaur, Sophie Krieger
Interpretation of variants of unknown significance (VUS) is a major challenge for laboratories performing molecular diagnosis of hereditary breast and ovarian cancer (HBOC), especially considering that many genes are now known to be involved in this syndrome. One important way these VUS can have a functional impact is through their effects on RNA splicing. Here we present a custom RNA-Seq assay plus bioinformatics and biostatistics pipeline to analyse specifically alternative and abnormal splicing junctions in 11 targeted HBOC genes...
October 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28884612/conjugation-with-20%C3%A2-kda-dextran-decreases-the-autoxidation-rate-of-bovine-hemoglobin
#18
Jun Zhang, Ying Wang, Guo-Xing You, Quan Wang, Shan Zhang, Wei-Li Yu, Tao Hu, Lian Zhao, Hong Zhou
Haemoglobin-based oxygen carrier (HBOC) is highly susceptible to autoxidation that renders a series of tissue and cellular toxicities. HBOC is prepared by chemical modification of haemoglobin (Hb), which typically increases the autoxidation rate of Hb. Thus, it is necessary to decrease the autoxidation of HBOC. In the present study, two dextran-bHb conjugates (dex20-bHb and dex40-bHb) were prepared by conjugation with 20 kDa or 40 kDa dextrans, where the thiol group of Cys-93(β) was reversibly protected...
September 8, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28833906/final-report-of-the-committee-on-gynecologic-oncology-the-japan-society-of-obstetrics-and-gynecology-on-a-fact-finding-questionnaire-on-the-status-of-treatment-of-hereditary-breast-and-ovarian-cancer-syndrome-in-japan
#19
Toyomi Satoh, Kiyoshi Takamatsu, Nobuhiro Takeshima, Hiroshi Kobayashi, Daisuke Aoki, Nao Suzuki
Hereditary breast and ovarian cancer syndrome (HBOC) is a hereditary tumor that can be definitively diagnosed by detection of germline mutation of the BRCA1 or BRCA2 gene. The HBOC Public Awareness and Management Sub-committee of the Tumor Committee, Japan Society of Obstetrics and Gynecology carried out a fact-finding survey on the status of treatment of HBOC in Japan. The directors of medical specialty teaching facilities were notified of the questionnaire by post, with the request for one respondent per facility...
August 17, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28807866/brca1-2-missense-mutations-and-the-value-of-in-silico-analyses
#20
Carolin E Sadowski, Daniela Kohlstedt, Cornelia Meisel, Katja Keller, Kerstin Becker, Luisa Mackenroth, Andreas Rump, Evelin Schröck, Pauline Wimberger, Karin Kast
INTRODUCTION: The clinical implications of genetic variants in BRCA1/2 in healthy and affected individuals are considerable. Variant interpretation, however, is especially challenging for missense variants. The majority of them are classified as variants of unknown clinical significance (VUS). Computational (in-silico) predictive programs are easy to access, but represent only one tool out of a wide range of complemental approaches to classify VUS. With this single-center study, we aimed to evaluate the impact of in-silico analyses in a spectrum of different BRCA1/2 missense variants...
August 12, 2017: European Journal of Medical Genetics
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