WorldWideScience

Sample records for clinically approved iron

  1. Cell tagging with clinically approved iron oxides: feasibility and effect of lipofection, particle size, and surface coating on labeling efficiency.

    Science.gov (United States)

    Matuszewski, Lars; Persigehl, Thorsten; Wall, Alexander; Schwindt, Wolfram; Tombach, Bernd; Fobker, Manfred; Poremba, Christopher; Ebert, Wolfgang; Heindel, Walter; Bremer, Christoph

    2005-04-01

    To evaluate the effect of lipofection, particle size, and surface coating on labeling efficiency of mammalian cells with superparamagnetic iron oxides (SPIOs). Institutional Review Board approval was not required. Different human cell lines (lung and breast cancer, fibrosarcoma, leukocytes) were tagged by using carboxydextran-coated SPIOs of various hydrodynamic diameters (17-65 nm) and a dextran-coated iron oxide (150 nm). Cells were incubated with increasing concentrations of iron (0.01-1.00 mg of iron [Fe] per milliliter), including or excluding a transfection medium (TM). Cellular iron uptake was analyzed qualitatively at light and electron microscopy and was quantified at atomic emission spectroscopy. Cell visibility was assessed with gradient- and spin-echo magnetic resonance (MR) imaging. Effects of iron concentration in the medium and of lipofection on cellular SPIO uptake were analyzed with analysis of variance and two-tailed Student t test, respectively. Iron oxide uptake increased in a dose-dependent manner with higher iron concentrations in the medium. The TM significantly increased the iron load of cells (up to 2.6-fold, P .05). As few as 10 000 cells could be detected with clinically available MR techniques by using this approach. Lipofection-based cell tagging is a simple method for efficient cell labeling with clinically approved iron oxide-based contrast agents. Large particle size and carboxydextran coating are preferable for cell tagging with endocytosis- and lipofection-based methods. (c) RSNA, 2005.

  2. Evaluation of Porcine Pancreatic Islets Transplanted in the Kidney Capsules of Diabetic Mice Using a Clinically Approved Superparamagnetic Iron Oxide (SPIO) and a 1.5T MR Scanner

    International Nuclear Information System (INIS)

    Kim, Hoe Suk; Kim, Hyoung Su; Park, Kyong Soo; Moon, Woo Kyung

    2010-01-01

    To evaluate transplanted porcine pancreatic islets in the kidney capsules of diabetic mice using a clinically approved superparamagnetic iron oxide (SPIO) and a 1.5T MR scanner. Various numbers of porcine pancreatic islets labeled with Resovist, a carboxydextran-coated SPIO, were transplanted into the kidney capsules of normal mice and imaged with a 3D FIESTA sequence using a 1.5T clinical MR scanner. Labeled (n = 3) and unlabeled (n = 2) islets were transplanted into the kidney capsules of streptozotocin-induced diabetic mice. Blood glucose levels and MR signal intensities were monitored for 30 days post-transplantation. There were no significant differences in viability or insulin secretion between labeled and unlabeled islets. A strong correlation (γ 2 > 0.94) was evident between the number of transplanted islets and T 2 relaxation times quantified by MRI. Transplantation with labeled or unlabeled islets helped restore normal sustained glucose levels in diabetic mice, and nephrectomies induced the recurrence of diabetes. The MR signal intensity of labeled pancreatic islets decreased by 80% over 30 days. The transplantation of SPIO-labeled porcine islets into the kidney capsule of diabetic mice allows to restore normal glucose levels, and these islets can be visualized and quantified using a 1.5T clinical MR scanner

  3. Iron deficiency and neurologic disease in children | Chiabi | Clinics ...

    African Journals Online (AJOL)

    Iron deficiency is a frequent disorder and a public health problem especially in children and pregnant women. The clinical manifestations are varied, and the most dreaded are neurologic. These neurologic manifestations are often missed as differential diagnosis in current clinical practice. The authors review iron ...

  4. Clinical consequences of iron overload in patients with myelodysplastic syndromes: the case for iron chelation therapy.

    Science.gov (United States)

    Shammo, Jamile M; Komrokji, Rami S

    2018-06-14

    Patients with myelodysplastic syndromes (MDS) are at increased risk of iron overload due to ineffective erythropoiesis and chronic transfusion therapy. The clinical consequences of iron overload include cardiac and/or hepatic failure, endocrinopathies, and infection risk. Areas covered: Iron chelation therapy (ICT) can help remove excess iron and ultimately reduce the clinical consequences of iron overload. The authors reviewed recent (last five years) English-language articles from PubMed on the topic of iron overload-related complications and the use of ICT (primarily deferasirox) to improve outcomes in patients with MDS. Expert Commentary: While a benefit of ICT has been more firmly established in other transfusion-dependent conditions such as thalassemia, its role in reducing iron overload in MDS remains controversial due to the lack of prospective controlled data demonstrating a survival benefit. Orally administered chelation agents (e.g., deferasirox), are now available, and observational and/or retrospective data support a survival benefit of using ICT in MDS. The placebo-controlled TELESTO trial (NCT00940602) is currently examining the use of deferasirox in MDS patients with iron overload, and is evaluating specifically whether use of ICT to alleviate iron overload can also reduce iron overload-related complications in MDS and improve survival.

  5. Intravenous Iron Administration and Hypophosphatemia in Clinical Practice

    Directory of Open Access Journals (Sweden)

    S. Hardy

    2015-01-01

    Full Text Available Introduction. Parenteral iron formulations are frequently used to correct iron deficiency anemia (IDA and iron deficiency (ID. Intravenous formulation efficacy on ferritin and hemoglobin level improvement is greater than that of oral formulations while they are associated with lower gastrointestinal side effects. Ferric carboxymaltose- (FCM- related hypophosphatemia is frequent and appears without clinical significance. The aim of this study was to assess the prevalence, duration, and potential consequences of hypophosphatemia after iron injection. Patients and Methods. The medical records of all patients who underwent parenteral iron injection between 2012 and 2014 were retrospectively reviewed. Pre- and postinjection hemoglobin, ferritin, plasma phosphate, creatinine, and vitamin D levels were assessed. Patients who developed moderate (range: 0.32–0.80 mmol/L or severe (<0.32 mmol/L hypophosphatemia were questioned for symptoms. Results. During the study period, 234 patients received iron preparations but 104 were excluded because of missing data. Among the 130 patients included, 52 received iron sucrose (FS and 78 FCM formulations. Among FS-treated patients, 22% developed hypophosphatemia versus 51% of FCM-treated patients, including 13% who developed profound hypophosphatemia. Hypophosphatemia severity correlated with the dose of FCM (p=0.04 but not with the initial ferritin, hemoglobin, or vitamin D level. Mean hypophosphatemia duration was 6 months. No immediate clinical consequence was found except for persistent fatigue despite anemia correction in some patients. Conclusions. Hypophosphatemia is frequent after parenteral FCM injection and may have clinical consequences, including persistent fatigue. Further studies of chronic hypophosphatemia long-term consequences, especially bone assessments, are needed.

  6. Integration of new technology into clinical practice after FDA approval.

    Science.gov (United States)

    Govil, Ashul; Hao, Steven C

    2016-10-01

    Development of new medical technology is a crucial part of the advancement of medicine and our ability to better treat patients and their diseases. This process of development is long and arduous and requires a significant investment of human, financial and material capital. However, technology development can be rewarded richly by its impact on patient outcomes and successful sale of the product. One of the major regulatory hurdles to technology development is the Food and Drug Administration (FDA) approval process, which is necessary before a technology can be marketed and sold in the USA. Many businesses, medical providers and consumers believe that the FDA approval process is the only hurdle prior to use of the technology in day-to-day care. In order for the technology to be adopted into clinical use, reimbursement for both the device as well as the associated work performed by physicians and medical staff must be in place. Work and coverage decisions require Current Procedural Terminology (CPT) code development and Relative Value Scale Update Committee (RUC) valuation determination. Understanding these processes is crucial to the timely availability of new technology to patients and providers. Continued and better partnerships between physicians, industry, regulatory bodies and payers will facilitate bringing technology to market sooner and ensure appropriate utilization.

  7. Setting up a randomized clinical trial in the UK: approvals and process.

    Science.gov (United States)

    Greene, Louise Eleanor; Bearn, David R

    2013-06-01

    Randomized clinical trials are considered the 'gold standard' in primary research for healthcare interventions. However, they can be expensive and time-consuming to set up and require many approvals to be in place before they can begin. This paper outlines how to determine what approvals are required for a trial, the background of each approval and the process for obtaining them.

  8. Role Strain in Collegiate Athletic Training Approved Clinical Instructors

    Science.gov (United States)

    Henning, Jolene M; Weidner, Thomas G

    2008-01-01

    Context: Certified athletic trainers who serve as Approved Clinical Instructors (ACIs) in the collegiate setting are balancing various roles (eg, patient care and related administrative tasks, clinical education). Whether this balancing act is associated with role strain in athletic trainers has not been examined. Objective: To examine the degree of, and contributing factors (eg, socialization experiences, professional and employment demographics, job congruency) to, role strain in collegiate ACIs. Design: Cross-sectional survey design. Setting: Geographically stratified random sample of ACIs affiliated with accredited athletic training education programs at National Collegiate Athletic Association (NCAA) Division I, II, and III institutions. Patients or Other Participants: 118 collegiate ACIs (47 head athletic trainers, 45 assistant athletic trainers, 26 graduate assistant athletic trainers). Main Outcome Measure(s): The Athletic Training ACI Role Strain Inventory, which measures total degree of role strain, 7 subscales of role strain, socialization experiences, professional and employment characteristics, and congruency in job responsibilities. Results: A total of 49% (n  =  58) of the participants experienced a moderate to high degree of role strain. Role Overload was the highest contributing subscale to total role strain. No differences were noted between total role strain and role occupant groups, NCAA division, or sex. Graduate assistant athletic trainers experienced a greater degree of role incompetence than head athletic trainers did (P  =  .001). Division II ACIs reported a greater degree of inter-role conflict than those in Division I (P  =  .02). Female ACIs reported a greater degree of role incompetence than male ACIs (P  =  .01). Those ACIs who stated that the ACI training provided by their institution did not adequately prepare them for the role as an ACI experienced greater role strain (P < .001). Conclusions: The ACIs in the

  9. Iron chelation therapy: clinical effectiveness, economic burden and quality of life in patients with iron overload.

    Science.gov (United States)

    Payne, Krista A; Rofail, Diana; Baladi, Jean-François; Viala, Muriel; Abetz, Linda; Desrosiers, Marie-Pierre; Lordan, Noreen; Ishak, Khajak; Proskorovsky, Irina

    2008-08-01

    This study of UK patients examines clinical, health-related quality of life (HRQOL) and economic outcomes associated with iron chelation therapy (ICT). Desferrioxamine (DFO) (Desferal; Novartis, Switzerland) and Deferiprone (Ferriprox; Apotex, Canada) are ICTs used to treat iron overload. DFO requires 8-to 12-hour infusions a minimum of five times per week. Deferiprone is administered in an oral daily regimen. Although pharmacologically efficacious, clinical effectiveness of ICT within the real-world setting is yet to be fully elucidated. A naturalistic cohort study of 60 patients (beta-thalassaemia, n=40; sickle cell disease, n=14; myelodysplastic syndromes, n=6; 63% female) receiving ICT in four UK treatment centres was conducted. Serum ferritin level data were abstracted from medical charts. Compliance, HRQOL, satisfaction and resource utilisation data were collected from interviews. Maximum ICT costs were estimated using the resource utilisation data associated with DFO. Mean serum ferritin levels, generally, remained elevated despite ICT. Compliance was suboptimal and HRQOL scores were lower than population norms. The total estimated mean weighted annual per-patient cost of DFO treatment was approximately pound19,000. DFO-related equipment, DFO drug, and home healthcare were estimated to account for 43%, 19% and 24% of costs, respectively. Other more minor components of total annual costs were for in-patient infusions, ICT home delivery services and monitoring costs. Generally, patients are not achieving target serum ferritin thresholds despite chronic treatment for iron overload. ICT appears to negatively impact HRQOL; compliance with ICT is poor; and, in the case of DFO, treatment costs well exceed the cost of DFO alone. These results suggest that current ICT in the real-world setting is suboptimal with respect to various clinical, HRQOL and economic outcomes.

  10. Iron

    Science.gov (United States)

    Iron is a mineral that our bodies need for many functions. For example, iron is part of hemoglobin, a protein which carries ... It helps our muscles store and use oxygen. Iron is also part of many other proteins and ...

  11. Modern iron replacement therapy: clinical and pathophysiological insights.

    Science.gov (United States)

    Girelli, Domenico; Ugolini, Sara; Busti, Fabiana; Marchi, Giacomo; Castagna, Annalisa

    2018-01-01

    Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era. In the meantime, advances in the pharmaceutical technologies are producing newer iron formulations aimed at minimizing the problems inherent with traditional approaches. The pharmacokinetic of oral and parenteral iron is substantially different, and diversities have become even clearer in light of the hepcidin master role in regulating systemic iron homeostasis. Here we review how iron therapy is changing because of such important advances in both pathophysiology and pharmacology.

  12. Hydroxyurea could be a good clinically relevant iron chelator.

    Science.gov (United States)

    Italia, Khushnooma; Colah, Roshan; Ghosh, Kanjaksha

    2013-01-01

    Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea therapy. Here we aimed to evaluate the efficacy of hydroxyurea alone and in combination with most widely used iron chelators like deferiprone and deferasirox for reducing iron from experimentally iron overloaded mice. 70 BALB/c mice received intraperitonial injections of iron-sucrose. The mice were then divided into 8 groups and were orally given hydroxyurea, deferiprone or deferasirox alone and their combinations for 4 months. CBC, serum-ferritin, TBARS, sTfr and hepcidin were evaluated before and after iron overload and subsequently after 4 months of drug therapy. All animals were then killed. Iron staining of the heart and liver tissue was done using Perl's Prussian Blue stain. Dry weight of iron in the heart and liver was determined by atomic absorption spectrometry. Increased serum-ferritin, TBARS, hepcidin and dry weight of iron in the liver and heart showed a significant reduction in groups treated with iron chelators with maximum reduction in the group treated with a combination of deferiprone, deferasirox and hydroxyurea. Thus hydroxyurea proves its role in reducing iron from iron overloaded mice. The iron chelating effect of these drugs can also be increased if given in combination.

  13. Hydroxyurea could be a good clinically relevant iron chelator.

    Directory of Open Access Journals (Sweden)

    Khushnooma Italia

    Full Text Available Our previous study showed a reduction in serum ferritin of β-thalassemia patients on hydroxyurea therapy. Here we aimed to evaluate the efficacy of hydroxyurea alone and in combination with most widely used iron chelators like deferiprone and deferasirox for reducing iron from experimentally iron overloaded mice. 70 BALB/c mice received intraperitonial injections of iron-sucrose. The mice were then divided into 8 groups and were orally given hydroxyurea, deferiprone or deferasirox alone and their combinations for 4 months. CBC, serum-ferritin, TBARS, sTfr and hepcidin were evaluated before and after iron overload and subsequently after 4 months of drug therapy. All animals were then killed. Iron staining of the heart and liver tissue was done using Perl's Prussian Blue stain. Dry weight of iron in the heart and liver was determined by atomic absorption spectrometry. Increased serum-ferritin, TBARS, hepcidin and dry weight of iron in the liver and heart showed a significant reduction in groups treated with iron chelators with maximum reduction in the group treated with a combination of deferiprone, deferasirox and hydroxyurea. Thus hydroxyurea proves its role in reducing iron from iron overloaded mice. The iron chelating effect of these drugs can also be increased if given in combination.

  14. Feedback in Clinical Education, Part I: Characteristics of Feedback Provided by Approved Clinical Instructors

    Science.gov (United States)

    Nottingham, Sara; Henning, Jolene

    2014-01-01

    Context Providing students with feedback is an important component of athletic training clinical education; however, little information is known about the feedback that Approved Clinical Instructors (ACIs; now known as preceptors) currently provide to athletic training students (ATSs). Objective To characterize the feedback provided by ACIs to ATSs during clinical education experiences. Design Qualitative study. Setting One National Collegiate Athletic Association Division I athletic training facility and 1 outpatient rehabilitation clinic that were clinical sites for 1 entry-level master's degree program accredited by the Commission on Accreditation of Athletic Training Education. Patients or Other Participants A total of 4 ACIs with various experience levels and 4 second-year ATSs. Data Collection and Analysis Extensive field observations were audio recorded, transcribed, and integrated with field notes for analysis. The constant comparative approach of open, axial, and selective coding was used to inductively analyze data and develop codes and categories. Member checking, triangulation, and peer debriefing were used to promote trustworthiness of the study. Results The ACIs gave 88 feedback statements in 45 hours and 10 minutes of observation. Characteristics of feedback categories included purpose, timing, specificity, content, form, and privacy. Conclusions Feedback that ACIs provided included several components that made each feedback exchange unique. The ACIs in our study provided feedback that is supported by the literature, suggesting that ACIs are using current recommendations for providing feedback. Feedback needs to be investigated across multiple athletic training education programs to gain more understanding of certain areas of feedback, including frequency, privacy, and form. PMID:24143902

  15. Iron

    DEFF Research Database (Denmark)

    Hansen, Jakob Bondo; Moen, I W; Mandrup-Poulsen, T

    2014-01-01

    and discuss recent evidence, suggesting that iron is a key pathogenic factor in both type 1 and type 2 diabetes with a focus on inflammatory pathways. Pro-inflammatory cytokine-induced β-cell death is not fully understood, but may include iron-induced ROS formation resulting in dedifferentiation by activation...... of transcription factors, activation of the mitochondrial apoptotic machinery or of other cell death mechanisms. The pro-inflammatory cytokine IL-1β facilitates divalent metal transporter 1 (DMT1)-induced β-cell iron uptake and consequently ROS formation and apoptosis, and we propose that this mechanism provides...

  16. Iron

    Science.gov (United States)

    ... Share: Search the ODS website Submit Search NIH Office of Dietary Supplements Consumer Datos en español Health ... eating a variety of foods, including the following: Lean meat, seafood, and poultry. Iron-fortified breakfast cereals ...

  17. Clinical outcomes of transfusion-associated iron overload in patients with refractory chronic anemia

    Directory of Open Access Journals (Sweden)

    Gao C

    2014-04-01

    Full Text Available Chong Gao, Li Li, Baoan Chen, Huihui Song, Jian Cheng, Xiaoping Zhang, Yunyu SunDepartment of Hematology and Oncology, Key Department of Jiangsu Medicine, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of ChinaBackground: The purpose of this study was to evaluate the clinical outcomes of transfusion-associated iron overload in patients with chronic refractory anemia.Methods: Clinical manifestations, main organ function, results of computed tomography (CT, endocrine evaluation, and serum ferritin levels were analyzed retrospectively in 13 patients who were transfusion-dependent for more than 1 year (receiving >50 units of red blood cells to determine the degree of iron overload and efficacy of iron-chelating therapy.Results: Serum ferritin levels increased to 1,830–5,740 ng/mL in all patients. Ten patients had abnormal liver function. The CT Hounsfield units in the liver increased significantly in eleven patients, and were proportional to their serum ferritin levels. Skin pigmentation, liver dysfunction, and endocrine dysfunction were observed in nine patients with serum ferritin >3,500 ng/mL, eight of whom have since died. Interestingly, serum ferritin levels did not decrease significantly in nine transfusion-dependent patients who had received 15–60 days of iron-chelating therapy.Conclusion: Transfusion-dependent patients may progress to secondary iron overload with organ impairment, which may be fatal in those who are heavily iron-overloaded. The CT Hounsfield unit is a sensitive indicator of iron overload in the liver. Iron chelation therapy should be initiated when serum ferritin is >1,000 ng/mL and continued until it is <1,000 ng/mL in transfusional iron-overloaded patients.Keywords: anemia, aplastic, iron overload, myelodysplastic syndromes

  18. Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies.

    Science.gov (United States)

    Miller, Jennifer E; Wilenzick, Marc; Ritcey, Nolan; Ross, Joseph S; Mello, Michelle M

    2017-12-05

    To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%-100%) of trials in patients were registered, 71% (IQR 57%-100%) reported results or shared a CSR synopsis, 80% (70%-100%) were published and 96% (80%-100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%-100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track

  19. Basic mechanisms of iron metabolism regulation and their clinical significance

    Directory of Open Access Journals (Sweden)

    L. M. Meshсheryakova

    2014-01-01

    Full Text Available This article is а composition of literature and experimental data of iron metabolism. There were studied the level of DMT-1, ferroportin, hepcidin at different stages of anemia and hemochromatosis. It is clear that the level of DMT-1 regulates by the hepcidin. Increaseing of the hepcidin concentration and decreasing DMT-1 level in patients with hemochromatosis explained good results of treatment.

  20. Basic mechanisms of iron metabolism regulation and their clinical significance

    Directory of Open Access Journals (Sweden)

    L. M. Meshсheryakova

    2015-01-01

    Full Text Available This article is а composition of literature and experimental data of iron metabolism. There were studied the level of DMT-1, ferroportin, hepcidin at different stages of anemia and hemochromatosis. It is clear that the level of DMT-1 regulates by the hepcidin. Increaseing of the hepcidin concentration and decreasing DMT-1 level in patients with hemochromatosis explained good results of treatment.

  1. Autosomal dominant polycystic kidney disease: recent advances in clinical management [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Zhiguo Mao

    2016-08-01

    Full Text Available The first clinical descriptions of autosomal dominant polycystic kidney disease (ADPKD go back at least 500 years to the late 16th century. Advances in understanding disease presentation and pathophysiology have mirrored the progress of clinical medicine in anatomy, pathology, physiology, cell biology, and genetics. The identification of PKD1 and PKD2, the major genes mutated in ADPKD, has stimulated major advances, which in turn have led to the first approved drug for this disorder and a fresh reassessment of patient management in the 21st century. In this commentary, we consider how clinical management is likely to change in the coming decade.

  2. Causes of iron overload in blood donors - a clinical study

    DEFF Research Database (Denmark)

    Laursen, A H; Bjerrum, O W; Friis-Hansen, L

    2018-01-01

    BACKGROUND AND OBJECTIVES: Despite the obligate iron loss from blood donation, some donors present with hyperferritinaemia that can result from a wide range of acute and chronic conditions including hereditary haemochromatosis (HH). The objective of our study was to investigate the causes...... of hyperferritinaemia in the blood donor population and explore the value of extensive HH mutational analyses. MATERIALS AND METHODS: Forty-nine consecutive donors (f = 6, m = 43) were included prospectively from the Capital Regional Blood Center. Inclusion criteria were a single ferritin value >1000 μg/l or repeated...... four donors had apparent alternative causes of hyperferritinaemia. CONCLUSION: HH-related mutations were the most frequent cause of hyperferritinaemia in a Danish blood donor population, and it appears that several different HH-genotypes can contribute to hyperferritinaemia. HH screening in blood...

  3. A Review of Clinical Data for Currently Approved Hysteroscopic Sterilization Procedures

    Science.gov (United States)

    Basinski, Cindy M

    2010-01-01

    Two hysteroscopic permanent sterilization procedures are approved for use in the United States: Essure® Permanent Birth Control System (Conceptus Incorporated, Mountain View, CA) and Adiana® Permanent Contraception (Hologic, Inc., Bedford, MA). This review compares the clinical trial data for these procedures. A notable difference is the resultant clinical pregnancy risk. The clinical trials for the Essure procedure have reported no pregnancies in 643 relying women in the 9 years since initiation of the studies. The clinical trial for the Adiana procedure has reported 12 pregnancies in 570 relying women in nearly 5 years of collected data. Other clinical outcome parameters concerning Essure and Adiana are examined in this review. PMID:21364861

  4. [Iron and invasive fungal infection].

    Science.gov (United States)

    Álvarez, Florencio; Fernández-Ruiz, Mario; Aguado, José María

    2013-01-01

    Iron is an essential factor for both the growth and virulence of most of microorganisms. As a part of the innate (or nutritional) immune system, mammals have developed different mechanisms to store and transport this element in order to limit free iron bioavailability. To survive in this hostile environment, pathogenic fungi have specific uptake systems for host iron sources, one of the most important of which is based on the synthesis of siderophores-soluble, low-molecular-mass, high-affinity iron chelators. The increase in free iron that results from iron-overload conditions is a well-established risk factor for invasive fungal infection (IFI) such as mucormycosis or aspergillosis. Therefore, iron chelation may be an appealing therapeutic option for these infections. Nevertheless, deferoxamine -the first approved iron chelator- paradoxically increases the incidence of IFI, as it serves as a xeno-siderophore to Mucorales. On the contrary, the new oral iron chelators (deferiprone and deferasirox) have shown to exert a deleterious effect on fungal growth both in vitro and in animal models. The present review focuses on the role of iron metabolism in the pathogenesis of IFI and summarises the preclinical data, as well as the limited clinical experience so far, in the use of new iron chelators as treatment for mucormycosis and invasive aspergillosis. Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  5. Gaps, tensions, and conflicts in the FDA approval process: implications for clinical practice.

    Science.gov (United States)

    Deyo, Richard A

    2004-01-01

    Despite many successes, drug approval at the Food and Drug Administration (FDA) is subject to gaps, internal tensions, and conflicts of interest. Recalls of drugs and devices and studies demonstrating advantages of older drugs over newer ones highlight the importance of these limitations. The FDA does not compare competing drugs and rarely requires tests of clinical efficacy for new devices. It does not review advertisements before use, assess cost-effectiveness, or regulate surgery (except for devices). Many believe postmarketing surveillance of drugs and devices is inadequate. A source of tension within the agency is pressure for speedy approvals. This may have resulted in "burn-out" among medical officers and has prompted criticism that safety is ignored. Others argue, however, that the agency is unnecessarily slow and bureaucratic. Recent reports identify conflicts of interest (stock ownership, consulting fees, research grants) among some members of the FDA's advisory committees. FDA review serves a critical function, but physicians should be aware that new drugs may not be as effective as old ones; that new drugs are likely to have undiscovered side effects at the time of marketing; that direct-to-consumer ads are sometimes misleading; that new devices generally have less rigorous evidence of efficacy than new drugs; and that value for money is not considered in approval.

  6. Clinical Significance of Reticulocyte Hemoglobin Content in the Diagnosis of Iron Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    Mustafa Karagülle

    2013-06-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the clinical significance of reticulocyte hemoglobin content (CHr in the diagnosis of iron deficiency anemia (IDA and to compare it with other conventional iron parameters. METHODS: A total of 32 female patients with IDA (serum hemoglobin 120 g/L and serum ferritin <20 ng/mL were enrolled. RESULTS: CHr was 24.95±3.92 pg in female patients with IDA and 29.93±2.96 pg in female patients with iron deficiency. CHr showed a significant positive correlation with hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, serum iron, and transferrin saturation and a significant negative correlation with transferrin and total iron-binding capacity. The cut-off value of CHr for detecting IDA was 29 pg. CONCLUSION: Our data demonstrate that CHr is a useful parameter that can be confidently used in the diagnosis of IDA, and a CHr cut-off value of 29 pg predicts IDA.

  7. Fate of clinical research studies after ethical approval--follow-up of study protocols until publication.

    Directory of Open Access Journals (Sweden)

    Anette Blümle

    Full Text Available Many clinical studies are ultimately not fully published in peer-reviewed journals. Underreporting of clinical research is wasteful and can result in biased estimates of treatment effect or harm, leading to recommendations that are inappropriate or even dangerous.We assembled a cohort of clinical studies approved 2000-2002 by the Research Ethics Committee of the University of Freiburg, Germany. Published full articles were searched in electronic databases and investigators contacted. Data on study characteristics were extracted from protocols and corresponding publications. We characterized the cohort, quantified its publication outcome and compared protocols and publications for selected aspects.Of 917 approved studies, 807 were started and 110 were not, either locally or as a whole. Of the started studies, 576 (71% were completed according to protocol, 128 (16% discontinued and 42 (5% are still ongoing; for 61 (8% there was no information about their course. We identified 782 full publications corresponding to 419 of the 807 initiated studies; the publication proportion was 52% (95% CI: 0.48-0.55. Study design was not significantly associated with subsequent publication. Multicentre status, international collaboration, large sample size and commercial or non-commercial funding were positively associated with subsequent publication. Commercial funding was mentioned in 203 (48% protocols and in 205 (49% of the publications. In most published studies (339; 81% this information corresponded between protocol and publication. Most studies were published in English (367; 88%; some in German (25; 6% or both languages (27; 6%. The local investigators were listed as (co-authors in the publications corresponding to 259 (62% studies.Half of the clinical research conducted at a large German university medical centre remains unpublished; future research is built on an incomplete database. Research resources are likely wasted as neither health care

  8. Feedback in Clinical Education, Part II: Approved Clinical Instructor and Student Perceptions of and Influences on Feedback

    Science.gov (United States)

    Nottingham, Sara; Henning, Jolene

    2014-01-01

    Context: Approved Clinical Instructors (ACIs; now known as preceptors) are expected to provide feedback to athletic training students (ATSs) during clinical education experiences. Researchers in other fields have found that clinical instructors and students often have different perceptions of actual and ideal feedback and that several factors may influence the feedback exchanges between instructors and students. However, understanding of these issues in athletic training education is minimal. Objective: To investigate the current characteristics and perceptions of and the influences on feedback exchanges between ATSs and ACIs. Design: Qualitative study. Setting: One entry-level master's degree program accredited by the Commission on Accreditation of Athletic Training Education. Patients or Other Participants: Four ACIs and 4 second-year ATSs. Data Collection and Analysis: Individual, semistructured interviews were conducted with participants and integrated with field notes and observations for analysis. We used the constant comparative approach to inductively analyze data and develop codes and categories. Member checking, triangulation, and peer debriefing were used to promote trustworthiness of the study. Results: Participants described that feedback plays an important role in clinical education and has several purposes related to improving performance. The ACIs and ATSs also discussed several preferred characteristics of feedback. Participants identified 4 main influences on their feedback exchanges, including the ACI, the ATS, personalities, and the learning environment. Conclusions: The ACIs and ATSs had similar perceptions of ideal feedback in addition to the actual feedback that was provided during their clinical education experiences. Most of the preferences for feedback were aligned with recommendations in the literature, suggesting that existing research findings are applicable to athletic training clinical education. Several factors influenced the

  9. Regulatory approvals in a large multinational clinical trial: the ESPRIT experience.

    Science.gov (United States)

    McNay, Laura A; Tavel, Jorge A; Oseekey, Karen; McDermott, Cathy M; Mollerup, David; Bebchuk, Judith D

    2002-02-01

    While accepted as serving an important function to safeguard human subjects, the process of obtaining regulatory approvals to conduct clinical trials is generally regarded as cumbersome and time-consuming. For large multinational trials, U.S. federally sponsored human subject research abroad involves specific U.S. regulatory requirements, in addition to those of the host country, that act as further hurdles. These requirements may include obtaining an Assurance of Protection for Human Subjects from the Office of Human Research Protection of the U.S. Department of Health and Human Services, maintaining specific Ethics Committee/Institutional Review Board (EC/IRB) composition, and incorporating mandated elements in informed consents, all of which may differ from local policies and guidelines. Specific examples of issues that led to delays in regulatory approvals for sites participating in the multinational clinical trial entitled Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT) are presented here. While the goal of these requirements is to protect the rights and welfare of human subjects, they may create substantial delays and engender resentment over the notion of lack of respect for individual country sovereignty. Substudies within ESPRIT have been undertaken to obtain feedback from EC/IRB chairpersons, site personnel responsible for processing the required assurances, ESPRIT investigators, and study participants regarding aspects of current U.S. regulatory requirements related to human subject protection and ethical issues in multinational research. The purpose of these substudies is to compare the attitudes and experiences across countries regarding important ethical issues associated with conducting ESPRIT. One objective of the substudies is to gather additional insight to the impact of U.S. regulatory processes. Another is to help to inform the debate about how to best maximize the rights and welfare of clinical trial

  10. Ethics approval in applications for open-access clinical trial data: An analysis of researcher statements to clinicalstudydatarequest.com.

    Directory of Open Access Journals (Sweden)

    Derek So

    Full Text Available Although there are a number of online platforms for patient-level clinical trial data sharing from industry sponsors, they are not very harmonized regarding the role of local ethics approval in the research proposal review process. The first and largest of these platforms is ClinicalStudyDataRequest.com (CSDR, which includes over three thousand trials from thirteen sponsors including GlaxoSmithKline, Novartis, Roche, Sanofi, and Bayer. CSDR asks applicants to state whether they have received ethics approval for their research proposal, but in most cases does not require that they submit evidence of approval. However, the website does require that applicants without ethical approval state the reason it was not required. In order to examine the perspectives of researchers on this topic, we coded every response to that question received by CSDR between June 2014 and February 2017. Of 111 applicants who stated they were exempt from ethics approval, 63% mentioned de-identification, 57% mentioned the use of existing data, 33% referred to local or jurisdictional regulations, and 20% referred to the approvals obtained by the original study. We conclude by examining the experience of CSDR within the broader context of the access mechanisms and policies currently being used by other data sharing platforms, and discuss how our findings might be used to help clinical trial data providers design clear and informative access documents.

  11. Supplementation of iron in pulmonary hypertension: Rationale and design of a phase II clinical trial in idiopathic pulmonary arterial hypertension

    Science.gov (United States)

    Howard, Luke S.G.E.; Watson, Geoffrey M.J.; Wharton, John; Rhodes, Christopher J.; Chan, Kakit; Khengar, Rajeshree; Robbins, Peter A.; Kiely, David G.; Condliffe, Robin; Elliott, Charlie A.; Pepke-Zaba, Joanna; Sheares, Karen; Morrell, Nicholas W.; Davies, Rachel; Ashby, Deborah; Gibbs, J. Simon R.; Wilkins, Martin R.

    2013-01-01

    Our aim is to assess the safety and potential clinical benefit of intravenous iron (Ferinject) infusion in iron deficient patients with idiopathic pulmonary arterial hypertension (IPAH). Iron deficiency in the absence of anemia (1) is common in patients with IPAH; (2) is associated with inappropriately raised levels of hepcidin, the key regulator of iron homeostasis; and (3) correlates with disease severity and worse clinical outcomes. Oral iron absorption may be impeded by reduced absorption due to elevated hepcidin levels. The safety and benefits of parenteral iron replacement in IPAH are unknown. Supplementation of Iron in Pulmonary Hypertension (SIPHON) is a Phase II, multicenter, double-blind, randomized, placebo-controlled, crossover clinical trial of iron in IPAH. At least 60 patients will be randomized to intravenous ferric carboxymaltose (Ferinject) or saline placebo with a crossover point after 12 weeks of treatment. The primary outcome will be the change in resting pulmonary vascular resistance from baseline at 12 weeks, measured by cardiac catheterization. Secondary measures include resting and exercise hemodynamics and exercise performance from serial bicycle incremental and endurance cardiopulmonary exercise tests. Other secondary measurements include serum iron indices, 6-Minute Walk Distance, WHO functional class, quality of life score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and cardiac anatomy and function from cardiac magnetic resonance. We propose that intravenous iron replacement will improve hemodynamics and clinical outcomes in IPAH. If the data supports a potentially useful therapeutic effect and suggest this drug is safe, the study will be used to power a Phase III study to address efficacy. PMID:23662181

  12. Characteristics of Clinical Studies Used for US Food and Drug Administration Approval of High-Risk Medical Device Supplements.

    Science.gov (United States)

    Zheng, Sarah Y; Dhruva, Sanket S; Redberg, Rita F

    2017-08-15

    High-risk medical devices often undergo modifications, which are approved by the US Food and Drug Administration (FDA) through various kinds of premarket approval (PMA) supplements. There have been multiple high-profile recalls of devices approved as PMA supplements. To characterize the quality of the clinical studies and data (strength of evidence) used to support FDA approval of panel-track supplements (a type of PMA supplement pathway that is used for significant changes in a device or indication for use and always requires clinical data). Descriptive study of clinical studies supporting panel-track supplements approved by the FDA between April 19, 2006, and October 9, 2015. Panel-track supplement approval. Methodological quality of studies including randomization, blinding, type of controls, clinical vs surrogate primary end points, use of post hoc analyses, and reporting of age and sex. Eighty-three clinical studies supported the approval of 78 panel-track supplements, with 71 panel-track supplements (91%) supported by a single study. Of the 83 studies, 37 (45%) were randomized clinical trials and 25 (30%) were blinded. The median number of patients per study was 185 (interquartile range, 75-305), and the median follow-up duration was 180 days (interquartile range, 84-270 days). There were a total of 150 primary end points (mean [SD], 1.8 [1.2] per study), and 57 primary end points (38%) were compared with controls. Of primary end points with controls, 6 (11%) were retrospective controls and 51 (89%) were active controls. One hundred twenty-one primary end points (81%) were surrogate end points. Thirty-three studies (40%) did not report age and 25 (30%) did not report sex for all enrolled patients. The FDA required postapproval studies for 29 of 78 (37%) panel-track supplements. Among clinical studies used to support FDA approval of high-risk medical device modifications, fewer than half were randomized, blinded, or controlled, and most primary outcomes were

  13. Clinical and radiologic review of uncommon cause of profound iron deficiency anemia: Median arcuate ligament syndrome

    International Nuclear Information System (INIS)

    Gunduz, Yasemin; Asil, Kiyasrttin; Aksoy, Yakup Ersel; Ayhan, Lacin Tatli

    2014-01-01

    Median arcuate ligament syndrome is an anatomic and clinical entity characterized by dynamic compression of the proximal celiac artery by the median arcuate ligament, which leads to postprandial epigastric pain, vomiting, and weight loss. These symptoms are usually nonspecific and are easily misdiagnosed as functional dyspepsia, peptic ulcer disease, or gastropathy. In this report, we presented a 72-year-old male patient with celiac artery compression syndrome causing recurrent abdominal pain associated with gastric ulcer and iron deficiency anemia. This association is relatively uncommon and therefore not well determined. In addition, we reported the CT angiography findings and three-dimensional reconstructions of this rare case.

  14. Clinical and radiologic review of uncommon cause of profound iron deficiency anemia: Median arcuate ligament syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Gunduz, Yasemin; Asil, Kiyasrttin; Aksoy, Yakup Ersel; Ayhan, Lacin Tatli [Dept. of Radiology, Sakarya University Medical Faculty, Sakarya (Turkmenistan)

    2014-08-15

    Median arcuate ligament syndrome is an anatomic and clinical entity characterized by dynamic compression of the proximal celiac artery by the median arcuate ligament, which leads to postprandial epigastric pain, vomiting, and weight loss. These symptoms are usually nonspecific and are easily misdiagnosed as functional dyspepsia, peptic ulcer disease, or gastropathy. In this report, we presented a 72-year-old male patient with celiac artery compression syndrome causing recurrent abdominal pain associated with gastric ulcer and iron deficiency anemia. This association is relatively uncommon and therefore not well determined. In addition, we reported the CT angiography findings and three-dimensional reconstructions of this rare case.

  15. Blockchain protocols in clinical trials: Transparency and traceability of consent [version 5; referees: 1 approved, 2 approved with reservations, 2 not approved

    Directory of Open Access Journals (Sweden)

    Mehdi Benchoufi

    2018-02-01

    Full Text Available Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient’s consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again.  We obtained a single document, in an open format, that accounted for the whole consent collection process: a time-stamped consent status regarding each version of the protocol. This document cannot be corrupted and can be checked on any dedicated public website. It should be considered a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened to remove the need for third parties, here trial stakeholders, and give participative control to the peer users. In the future, the complex data flow of a clinical trial could be tracked by using Blockchain, which core functionality, named Smart Contract, could help prevent clinical trial events not occurring in the correct chronological order, for example including patients before they consented or analysing case report form data before freezing the database. Globally, Blockchain could help with reliability, security

  16. Blockchain protocols in clinical trials: Transparency and traceability of consent [version 4; referees: 1 approved, 2 approved with reservations, 2 not approved

    Directory of Open Access Journals (Sweden)

    Mehdi Benchoufi

    2017-12-01

    Full Text Available Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient’s consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again.  We obtained a single document, in an open format, that accounted for the whole consent collection process: a time-stamped consent status regarding each version of the protocol. This document cannot be corrupted and can be checked on any dedicated public website. It should be considered a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened to remove the need for third parties, here trial stakeholders, and give participative control to the peer users. In the future, the complex data flow of a clinical trial could be tracked by using Blockchain, which core functionality, named Smart Contract, could help prevent clinical trial events not occurring in the correct chronological order, for example including patients before they consented or analysing case report form data before freezing the database. Globally, Blockchain could help with reliability, security

  17. Blockchain protocols in clinical trials: Transparency and traceability of consent [version 3; referees: 1 approved, 2 approved with reservations, 1 not approved

    Directory of Open Access Journals (Sweden)

    Mehdi Benchoufi

    2017-07-01

    Full Text Available Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing the collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we will built a consent workflow using a rising technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient’s consent collection using Blockchain; thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each revision of the protocol, consent was sought again. We obtained a single document, in a standard open format, that accounted for the whole consent collection process: timestamped consent status with regards to each version of the protocol. This document cannot be corrupted, and can be checked on any dedicated public website. It should be considered as a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened in order to remove the need for third parties, here the trial stakeholders, and give participative control to the peer-to-peer users. In the future, we think that the complex data flow of a clinical trial can be tracked using Blockchain, that a blockchain core functionality, named Smart Contract, could help prevent clinical trial events not to happen in the right chronological order: for example including patients before they consented or analysing case report forms data before freezing the database

  18. Blockchain protocols in clinical trials: Transparency and traceability of consent [version 3; referees: 1 approved, 2 approved with reservations, 1 not approved

    OpenAIRE

    Mehdi Benchoufi; Raphael Porcher; Philippe Ravaud

    2017-01-01

    Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing the collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we will built a consent workflow using a rising technology called Blockchain. This is a...

  19. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations.

    Science.gov (United States)

    Mold, Matthew; Shardlow, Emma; Exley, Christopher

    2016-08-12

    Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al(3+) in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, potentially generating a greater inflammatory response at the site of simulated injection. The cellular uptake of aluminium based adjuvants (ABAs) used in clinically approved vaccinations are compared to a commonly used experimental ABA, in an in vitro THP-1 cell model. Using lumogallion as a direct-fluorescent molecular probe for aluminium, complemented with transmission electron microscopy provides further insight into the morphology of internalised particulates, driven by the physicochemical variations of the ABAs investigated. We demonstrate that not all aluminium adjuvants are equal neither in terms of their physical properties nor their biological reactivity and potential toxicities both at the injection site and beyond. High loading of aluminium oxyhydroxide in the cytoplasm of THP-1 cells without immediate cytotoxicity might predispose this form of aluminium adjuvant to its subsequent transport throughout the body including access to the brain.

  20. The emergence of diagnostic imaging technologies in breast cancer: discovery, regulatory approval, reimbursement, and adoption in clinical guidelines.

    Science.gov (United States)

    Gold, Laura S; Klein, Gregory; Carr, Lauren; Kessler, Larry; Sullivan, Sean D

    2012-01-25

    In this article, we trace the chronology of developments in breast imaging technologies that are used for diagnosis and staging of breast cancer, including mammography, ultrasonography, magnetic resonance imaging, computed tomography, and positron emission tomography. We explore factors that affected clinical acceptance and utilization of these technologies from discovery to clinical use, including milestones in peer-reviewed publication, US Food and Drug Administration approval, reimbursement by payers, and adoption into clinical guidelines. The factors driving utilization of new imaging technologies are mainly driven by regulatory approval and reimbursement by payers rather than evidence that they provide benefits to patients. Comparative effectiveness research can serve as a useful tool to investigate whether these imaging modalities provide information that improves patient outcomes in real-world settings.

  1. Analysis of iron acquisition and storage-related genes in clinical and non-clinical strains of Yersinia enterocolitica biovar 1A.

    Science.gov (United States)

    Kanaujia, Pawan Kumar; Bajaj, Priyanka; Virdi, Jugsharan Singh

    2015-10-01

    Possession of mechanisms for iron acquisition and its storage enhances the ability of the bacteria to survive in the iron-limiting environment of the host. In this study, 81 strains of Yersinia enterocolitica biovar 1A isolated from various clinical (n = 51) and non-clinical (n = 30) sources were investigated for the presence of the genes related to iron acquisition and storage. Important genes which were present in more than 85% of the strains included hasA, foxA, bfr, bfd, ftnA, and hmsT as well as the fhuCDB, fepBDGCfesfepA, feoAB, yfuABCD, hemPRSTUV, and hmsHFRS gene clusters. Majority of these genes is being reported for the first time in biovar 1A strains and showed significant homology with genes present in the known pathogenic biovars of Y. enterocolitica. However, no significant difference was observed in the distribution of iron acquisition and storage-related genes among clinical and non-clinical biovar 1A strains. Thus, it may be suggested that the presence of iron acquisition and storage-related genes per se might not be responsible for the supposedly better ability of clinical biovar 1A strains to cause infections in humans. However, in the backdrop of this data, the need to undertake functional studies are highly recommended. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  2. Pica associated with iron deficiency or depletion: clinical and laboratory correlates in 262 non-pregnant adult outpatients

    Directory of Open Access Journals (Sweden)

    Barton James C

    2010-12-01

    Full Text Available Abstract Background There are many descriptions of the association of pica with iron deficiency in adults, but there are few reports in which observations available at diagnosis of iron deficiency were analyzed using multivariable techniques to identify significant predictors of pica. We sought to identify clinical and laboratory correlates of pica in adults with iron deficiency or depletion using univariable and stepwise forward logistic regression analyses. Methods We reviewed charts of 262 non-pregnant adult outpatients (ages ≥18 y who required treatment with intravenous iron dextran. We tabulated their sex, age, race/ethnicity, body mass index, symptoms and causes of iron deficiency or depletion, serum iron and complete blood count measures, and other conditions at diagnosis before intravenous iron dextran was administered. We excluded patients with serum creatinine >133 μmol/L or disorders that could affect erythrocyte or iron measures. Iron deficiency was defined as both SF Results There were 230 women (184 white, 46 black; ages 19-91 y and 32 men (31 white, 1 black; ages 24-81 y. 118 patients (45.0% reported pica; of these, 87.3% reported ice pica (pagophagia. In univariable analyses, patients with pica had lower mean age, black race/ethnicity, and higher prevalences of cardiopulmonary and epithelial manifestations. The prevalence of iron deficiency, with or without anemia, did not differ significantly between patients with and without pica reports. Mean hemoglobin and mean corpuscular volume (MCV were lower and mean red blood cell distribution width (RDW and platelet count were higher in patients with pica. Thrombocytosis occurred only in women and was more prevalent in those with pica (20.4% vs. 8.3%; p = 0.0050. Mean total iron-binding capacity was higher and mean serum ferritin was lower in patients with pica. Nineteen patients developed a second episode of iron deficiency or depletion; concordance of recurrent pica (or absence of

  3. Effect of clinically approved HDAC inhibitors on Plasmodium, Leishmania and Schistosoma parasite growth.

    Science.gov (United States)

    Chua, Ming Jang; Arnold, Megan S J; Xu, Weijun; Lancelot, Julien; Lamotte, Suzanne; Späth, Gerald F; Prina, Eric; Pierce, Raymond J; Fairlie, David P; Skinner-Adams, Tina S; Andrews, Katherine T

    2017-04-01

    Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin) that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L. donovani parasites and two for in vivo activity in a mouse malaria model. All four compounds were potent inhibitors of P. knowlesi malaria parasites (IC 50 9-370 nM), with belinostat, panobinostat and vorinostat having 8-45 fold selectivity for the parasite over human neonatal foreskin fibroblast (NFF) or human embryonic kidney (HEK 293) cells, while romidepsin was not selective. Each of the HDAC inhibitor drugs caused hyperacetylation of P. knowlesi histone H4. None of the drugs was active against Leishmania amastigote or promastigote parasites (IC 50  > 20 μM) or S. mansoni schistosomula (IC 50  > 10 μM), however romidepsin inhibited S. mansoni adult worm parings and egg production (IC 50 ∼10 μM). Modest in vivo activity was observed in P. berghei infected mice dosed orally with vorinostat or panobinostat (25 mg/kg twice daily for four days), with a significant reduction in parasitemia observed on days 4-7 and 4-10 after infection (P < 0.05), respectively. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Effect of clinically approved HDAC inhibitors on Plasmodium, Leishmania and Schistosoma parasite growth

    Directory of Open Access Journals (Sweden)

    Ming Jang Chua

    2017-04-01

    Full Text Available Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L. donovani parasites and two for in vivo activity in a mouse malaria model. All four compounds were potent inhibitors of P. knowlesi malaria parasites (IC50 9–370 nM, with belinostat, panobinostat and vorinostat having 8–45 fold selectivity for the parasite over human neonatal foreskin fibroblast (NFF or human embryonic kidney (HEK 293 cells, while romidepsin was not selective. Each of the HDAC inhibitor drugs caused hyperacetylation of P. knowlesi histone H4. None of the drugs was active against Leishmania amastigote or promastigote parasites (IC50 > 20 μM or S. mansoni schistosomula (IC50 > 10 μM, however romidepsin inhibited S. mansoni adult worm parings and egg production (IC50 ∼10 μM. Modest in vivo activity was observed in P. berghei infected mice dosed orally with vorinostat or panobinostat (25 mg/kg twice daily for four days, with a significant reduction in parasitemia observed on days 4–7 and 4–10 after infection (P < 0.05, respectively.

  5. THE BIG PICTURE ON SMALL MEDICINE: THE STATE OF NANOMEDICINE PRODUCTS APPROVED FOR USE OR IN CLINICAL TRIALS

    Science.gov (United States)

    Etheridge, Michael L.; Campbell, Stephen A.; Erdman, Arthur G.; Haynes, Christy L.; Wolf, Susan M.; McCullough, Jeffrey

    2015-01-01

    Developments in nanomedicine are expected to provide solutions to many of modern medicine’s unsolved problems, so it is no surprise that literature is flush with articles discussing the subject. However, existing reviews tend to focus on specific sectors of nanomedicine or take a very forward looking stance and fail to provide a complete perspective on the current landscape. This article provides a more comprehensive and contemporary inventory of nanomedicine products. A keyword search of literature, clinical trial registries, and the Web, yielded 247 nanomedicine products that are approved or in various stages of clinical study. Specific information on each was gathered, so the overall field could be described based on various dimensions, including: FDA classification, approval status, nanoscale size, treated condition, nanostructure, and others. In addition to documenting the large number of nanomedicine products already in human use, this study indentifies some interesting trends forecasting the future of nanomedicine. PMID:22684017

  6. Molecular and parametric imaging with iron oxides

    International Nuclear Information System (INIS)

    Matuszewski, L.; Bremer, C.; Tombach, B.; Heindel, W.

    2007-01-01

    Superparamagnetic iron oxide (SPIO) contrast agents, clinically established for high resolution magnetic resonance imaging of reticuloendothelial system containing anatomical structures, can additionally be exploited for the non-invasive characterization and quantification of pathology down to the molecular level. In this context, SPIOs can be applied for non-invasive cell tracking, quantification of tissue perfusion and target specific imaging, as well as for the detection of gene expression. This article provides an overview of new applications for clinically approved iron oxides as well of new, modified SPIO contrast agents for parametric and molecular imaging. (orig.) [de

  7. Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

    Science.gov (United States)

    Haldar, Swati; Tripathi, Ajai K.; Horback, Katharine; Wong, Joseph; Sharma, Deepak; Beserra, Amber; Suda, Srinivas; Anbalagan, Charumathi; Dev, Som; Mukhopadhyay, Chinmay K.; Singh, Ajay

    2014-01-01

    Abstract Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mis-metabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders. Antioxid. Redox Signal. 20, 1324–1363. PMID:23815406

  8. Assessing the potential clinical impact of reciprocal drug approval legislation on access to novel therapeutics in the USA: a cohort study.

    Science.gov (United States)

    Larochelle, Matthieu; Downing, Nicholas S; Ross, Joseph S; David, Frank S

    2017-02-08

    To quantify the potential effect of reciprocal approval legislation on access to clinically impactful therapeutics in the USA. A cohort study. New therapeutics approved by the Food and Drug Administration (FDA), European Medicines Agency (EMA) and/or Health Canada between 2000 and 2010. Characteristics of new therapeutics approved by the EMA and/or Health Canada before the FDA, including mechanistic novelty, likely clinical impact, size of the affected population and FDA review outcome. From 2001 to 2010, 282 drugs were approved in the USA, Europe or Canada, including 172 (61%) first approved in the USA, 24 (9%) never approved in the USA, and 86 (30%) approved in the USA after Europe and/or Canada. Of the 110 new drugs approved in Europe and/or Canada before the USA, 37 (34%) had a novel mechanisms of action compared with drugs already approved by the FDA, but only 10 (9%) were for conditions lacking alternate available therapies in the USA at the time of ex-US approval-of which the majority (9/10; 90%) were indicated for rare diseases. 12 of the 37 agents with novel mechanisms of action approved first in Europe and/or Canada (32%) had their initial FDA submissions rejected for safety reasons-including 2 drugs that were ultimately withdrawn from the market in Europe due to safety concerns. If enacted, reciprocal approval legislation would most likely benefit only a small number of US patients receiving treatment for rare diseases, and the benefit may be somewhat mitigated by an increased exposure to harms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  9. Prenatal Iron Supplementation Reduces Maternal Anemia, Iron Deficiency, and Iron Deficiency Anemia in a Randomized Clinical Trial in Rural China, but Iron Deficiency Remains Widespread in Mothers and Neonates.

    Science.gov (United States)

    Zhao, Gengli; Xu, Guobin; Zhou, Min; Jiang, Yaping; Richards, Blair; Clark, Katy M; Kaciroti, Niko; Georgieff, Michael K; Zhang, Zhixiang; Tardif, Twila; Li, Ming; Lozoff, Betsy

    2015-08-01

    Previous trials of prenatal iron supplementation had limited measures of maternal or neonatal iron status. The purpose was to assess effects of prenatal iron-folate supplementation on maternal and neonatal iron status. Enrollment occurred June 2009 through December 2011 in Hebei, China. Women with uncomplicated singleton pregnancies at ≤20 wk gestation, aged ≥18 y, and with hemoglobin ≥100 g/L were randomly assigned 1:1 to receive daily iron (300 mg ferrous sulfate) or placebo + 0.40 mg folate from enrollment to birth. Iron status was assessed in maternal venous blood (at enrollment and at or near term) and cord blood. Primary outcomes were as follows: 1) maternal iron deficiency (ID) defined in 2 ways as serum ferritin (SF) iron (BI) anemia [ID + anemia (IDA); hemoglobin 118 μmol/mol). A total of 2371 women were randomly assigned, with outcomes for 1632 women or neonates (809 placebo/folate, 823 iron/folate; 1579 mother-newborn pairs, 37 mothers, 16 neonates). Most infants (97%) were born at term. At or near term, maternal hemoglobin was significantly higher (+5.56 g/L) for iron vs. placebo groups. Anemia risk was reduced (RR: 0.53; 95% CI: 0.43, 0.66), as were risks of ID (RR: 0.74; 95% CI: 0.69, 0.79 by SF; RR: 0.65; 95% CI: 0.59, 0.71 by BI) and IDA (RR: 0.49; 95% CI: 0.38, 0.62 by SF; RR: 0.51; 95% CI: 0.40, 0.65 by BI). Most women still had ID (66.8% by SF, 54.7% by BI). Adverse effects, all minor, were similar by group. There were no differences in cord blood iron measures; >45% of neonates in each group had ID. However, dose-response analyses showed higher cord SF with more maternal iron capsules reported being consumed (β per 10 capsules = 2.60, P iron supplementation reduced anemia, ID, and IDA in pregnant women in rural China, but most women and >45% of neonates had ID, regardless of supplementation. This trial was registered at clinicaltrials.gov as NCT02221752. © 2015 American Society for Nutrition.

  10. Heterogeneity of Clinical Trials for Antihypertensive Drugs in Japan: Exploratory Analysis of Confirmatory Phase III Trials Used for Marketing Approval.

    Science.gov (United States)

    Kaneko, Reina; Sano, Kota; Ono, Shunsuke

    2018-07-01

    The results of pivotal trials, which provide a rationale for marketing approval decisions for new drugs, are considered for various comparative purposes in postmarketing analyses. Using meta-regression analysis of 91 randomized controlled trials of 61 approved antihypertensive drugs in Japan, we show that mean baseline blood pressure (BP) of each arm was associated with predetermined entry criteria (EC), age, and trial start year (TSY). BP changes following treatment were associated with EC, subject characteristics (e.g., age, complications, baseline BP), study design (e.g., concomitant drug use), and TSY. Effect sizes were generally larger in trials for the first and second drugs in the same class than in trials for follow-on drugs. Results of pivotal trials may vary depending on many factors, suggesting possible challenges associated with the comparison of these results indirectly. Due to the heterogeneity in pivotal trials, caution should be exercised when comparing approved drugs and conducting meta-analyses retrospectively. © 2017, The American Society for Clinical Pharmacology and Therapeutics.

  11. Efficacy and Tolerability of Intravenous Ferric Carboxymaltose in Patients with Iron Deficiency at a Hospital Outpatient Clinic: A Retrospective Cohort Study of Real-World Clinical Practice

    Directory of Open Access Journals (Sweden)

    António Robalo Nunes

    2017-01-01

    Full Text Available Ferric carboxymaltose (FCM is an intravenous iron formulation to correct iron deficiency. Although its use has been extensively studied in clinical trials, real-world evidence regarding FCM treatment is scarce. Our aim was to evaluate the efficacy and tolerability of FCM treatment in patients with iron deficiency, with or without anemia, at a hospital outpatient clinic. Data was collected retrospectively from medical records. During this 2-year study, 459 patients were included. Mean age was 58.6 ± 17.5 years and most patients received cumulative FCM doses of 501–1000 mg (63.2%. Six weeks after administration of FCM, efficacy endpoints hemoglobin increase ≥2 g/dL, hemoglobin increase ≥3 g/dL, and transferrin saturation > 20% were attained by 41%, 20%, and 63% of patients, respectively. Patients who received higher FCM doses showed significant reduced odds of not achieving hemoglobin increase ≥2 g/dL (501–1000 mg, adjusted odds ratio [OR]: 0.34, 95% confidence interval [CI] 0.18–0.62; 1001–3000 mg, OR: 0.19, 95% CI 0.07–0.49, compared to 500 mg doses. Treatment-emergent adverse events were documented in <4% of patients. In conclusion, FCM treatment was effective and well-tolerated by outpatients with iron deficiency at a hospital clinic, and its dosage should be adjusted to improve iron deficiency management in clinical practice.

  12. Identification and content validation of wound therapy clinical endpoints relevant to clinical practice and patient values for FDA approval. Part 1. Survey of the wound care community.

    Science.gov (United States)

    Driver, Vickie R; Gould, Lisa J; Dotson, Peggy; Gibbons, Gary W; Li, William W; Ennis, William J; Kirsner, Robert S; Eaglstein, William H; Bolton, Laura L; Carter, Marissa J

    2017-05-01

    Wounds that exhibit delayed healing add extraordinary clinical, economic, and personal burdens to patients, as well as to increasing financial costs to health systems. New interventions designed to ease such burdens for patients with cancer, renal, or ophthalmologic conditions are often cleared for approval by the U.S. Food and Drug Administration (FDA) using multiple endpoints but the requirement of complete healing as a primary endpoint for wound products impedes FDA clearance of interventions that can provide other clinical or patient-centered benefits for persons with wounds. A multidisciplinary group of wound experts undertook an initiative, in collaboration with the FDA, to identify and content validate supporting FDA criteria for qualifying wound endpoints relevant to clinical practice (CP) and patient-centered outcomes (PCO) as primary outcomes in clinical trials. As part of the initiative, a research study was conducted involving 628 multidisciplinary expert wound clinicians and researchers from 4 different groups: the interdisciplinary core advisory team; attendees of the Spring 2015 Symposium on Advanced Wound Care (SAWC); clinicians employed by a national network of specialty clinics focused on comprehensive wound care; and Association for the Advancement of Wound Care (AAWC) and Wound Healing Society (WHS) members who had not previously completed the survey. The online survey assessed 28 literature-based wound care endpoints for their relevance and importance to clinical practice and clinical research. Fifteen of the endpoints were evaluated for their relevance to improving quality of life. Twenty-two endpoints had content validity indexes (CVI) ≥ 0.75, and 15 were selected as meriting potential inclusion as additional endpoints for FDA approval of future wound care interventions. This study represents an important first step in identifying and validating new measurable wound care endpoints for clinical research and practice and for regulatory

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children who do not consume the daily recommended amount of iron. Read less Participate in NHLBI Clinical Trials We lead or sponsor many studies related to iron-deficiency anemia. See if you ...

  14. Update on the use of deferasirox in the management of iron overload

    Directory of Open Access Journals (Sweden)

    Ali Taher

    2009-10-01

    Full Text Available Ali Taher,1 Maria Domenica Cappellini21American University of Beirut, Beirut, Lebanon; 2Universitá di Milano, Policlinico Foundation IRCCS, Milan, ItalyAbstract: Regular blood transfusions as supportive care for patients with chronic anemia inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload cause significant morbidity and mortality if not effectively treated with chelation therapy. Based on a comprehensive clinical development program, the once-daily, oral iron chelator deferasirox (Exjade® is approved for the treatment of transfusional iron overload in adult and pediatric patients with various transfusion-dependent anemias, including β-thalassemia and the myelodysplastic syndromes. Deferasirox dose should be titrated for each individual patient based on transfusional iron intake, current iron burden and whether the goal is to decrease or maintain body iron levels. Doses of >30 mg/kg/day have been shown to be effective with a safety profile consistent with that observed at doses <30 mg/kg/day. Recent data have highlighted the ability of deferasirox to decrease cardiac iron levels and to prevent the accumulation of iron in the heart. The long-term efficacy and safety of deferasirox for up to 5 years of treatment have now been established. The availability of this effective and generally well tolerated oral therapy represents a significant advance in the management of transfusional iron overload. Keywords: deferasirox, Exjade, oral, iron chelation, iron overload, cardiac iron 

  15. Iron deficiency intravenous substitution in a Swiss academic primary care division: analysis of practices

    Science.gov (United States)

    Varcher, Monica; Zisimopoulou, Sofia; Braillard, Olivia; Favrat, Bernard; Junod Perron, Noëlle

    2016-01-01

    Background Iron deficiency is a common problem in primary care and is usually treated with oral iron substitution. With the recent simplification of intravenous (IV) iron administration (ferric carboxymaltose) and its approval in many countries for iron deficiency, physicians may be inclined to overutilize it as a first-line substitution. Objective The aim of this study was to evaluate iron deficiency management and substitution practices in an academic primary care division 5 years after ferric carboxymaltose was approved for treatment of iron deficiency in Switzerland. Methods All patients treated for iron deficiency during March and April 2012 at the Geneva University Division of Primary Care were identified. Their medical files were analyzed for information, including initial ferritin value, reasons for the investigation of iron levels, suspected etiology, type of treatment initiated, and clinical and biological follow-up. Findings were assessed using an algorithm for iron deficiency management based on a literature review. Results Out of 1,671 patients, 93 were treated for iron deficiency. Median patients’ age was 40 years and 92.5% (n=86) were female. The average ferritin value was 17.2 μg/L (standard deviation 13.3 μg/L). The reasons for the investigation of iron levels were documented in 82% and the suspected etiology for iron deficiency was reported in 67%. Seventy percent of the patients received oral treatment, 14% IV treatment, and 16% both. The reasons for IV treatment as first- and second-line treatment were reported in 57% and 95%, respectively. Clinical and biological follow-up was planned in less than two-thirds of the cases. Conclusion There was no clear overutilization of IV iron substitution. However, several steps of the iron deficiency management were not optimally documented, suggesting shortcuts in clinical reasoning. PMID:27445502

  16. Case studies on clinical evaluation of biosimilar monoclonal antibody: scientific considerations for regulatory approval.

    Science.gov (United States)

    Kudrin, Alex; Knezevic, Ivana; Joung, Jeewon; Kang, Hye-Na

    2015-01-01

    The objective of this paper is to provide considerations based on comprehensive case studies important for regulatory evaluation of monoclonal antibodies as similar biotherapeutic products (SBPs) with a special emphasis on clinical aspects. Scientific principles from WHO Guidelines on SBPs were used as a basis for the exercise. Working groups consisted of regulators, manufacturers and academia. The following topics were discussed by the working groups: clinical criteria for biosimilarity, extrapolation approach and the overall regulatory decision making process. In order to determine typical pitfalls in the design of a SBP clinical programme and evaluate the gap of knowledge, amongst different industry and regulatory stakeholders on the appraisal of the data arising from SBP clinical studies, we have presented two fictional but realistic clinical case studies. The first case consists of the fictional development programme for an infliximab SBP candidate. The second case describes clinical studies proposed for a fictional rituximab SBP candidate. In the first scenario a highly similar quality profile has been taken forward into clinical studies whereas there was an important residual difference in functional attributes for the rituximab SBP candidate. These case studies were presented at the WHO implementation workshop for the WHO guidelines on evaluation of similar biotherapeutic products held in Seoul, Republic of Korea, in May 2014. The goal was to illustrate the interpretation of the clinical data arising from studies with SBP candidates and elicit knowledge gaps in clinical assessment. This paper reflects the outcome of the exercise and discussions held in Seoul and offers an analysis of the case studies as a learning opportunity on clinical development and evaluation of SBPs. Copyright © 2014 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  17. Approval procedures for clinical trials in the field of radiation oncology; Genehmigungsverfahren klinischer Studien im Bereich der Radioonkologie

    Energy Technology Data Exchange (ETDEWEB)

    Simon, Monique; Buettner, Daniel [Deutsches Konsortium fuer Translationale Krebsforschung (DKTK), Dresden (Germany); Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany); Medizinische Fakultaet und Universitaetsklinikum Carl Gustav Carus, Technische Universitaet Dresden, Klinik fuer Strahlentherapie und Radioonkologie und OncoRay - Nationales Zentrum fuer Strahlenforschung in der Onkologie, Dresden (Germany); Habeck, Matthias; Habeck, Uta; Brix, Gunnar [Bundesamt fuer Strahlenschutz (BfS), Fachbereich Strahlenschutz und Gesundheit, Neuherberg (Germany); Krause, Mechthild; Baumann, Michael [Deutsches Konsortium fuer Translationale Krebsforschung (DKTK), Dresden (Germany); Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany); Medizinische Fakultaet und Universitaetsklinikum Carl Gustav Carus, Technische Universitaet Dresden, Klinik fuer Strahlentherapie und Radioonkologie und OncoRay - Nationales Zentrum fuer Strahlenforschung in der Onkologie, Dresden (Germany); Helmholtz-Zentrum Dresden - Rossendorf, Institut fuer Radioonkologie und OncoRay - Nationales Zentrum fuer Strahlenforschung in der Onkologie, Dresden (Germany); Willich, Normann [Universitaetsklinikum Muenster, Klinik fuer Strahlentherapie - Radioonkologie, Muenster (Germany); Wenz, Frederik [Universitaetsmedizin Mannheim, Medizinische Fakultaet Mannheim, Universitaet Heidelberg, Klinik fuer Strahlentherapie und Radioonkologie, Mannheim (Germany); Schmidberger, Heinz [Universitaetsmedizin Mainz, Klinik fuer Radioonkologie und Strahlentherapie, Mainz (Germany); Debus, Juergen [Universitaetsklinikum Heidelberg, Klinik fuer Radioonkologie und Strahlentherapie, Heidelberg (Germany); Noelling, Torsten

    2015-12-15

    Application of ionizing radiation for the purpose of medical research in Germany needs to be approved by the national authority for radiation protection (Bundesamt fuer Strahlenschutz, BfS). For studies in the field of radiation oncology, differentiation between use of radiation for ''medical care (Heilkunde)'' versus ''medical research'' frequently leads to contradictions. The aim of this article is to provide principle investigators, individuals, and institutions involved in the process, as well as institutional review or ethics committees, with the necessary information for this assessment. Information on the legal frame and the approval procedures are also provided. A workshop was co-organized by the German Society for Radiation Oncology (DEGRO), the Working Party for Radiation Oncology (ARO) of the German Cancer Society (DKG), the German Society for Medical Physics (DGMP), and the German Cancer Consortium (DKTK) in October 2013. This paper summarizes the results of the workshop and the follow-up discussions between the organizers and the BfS. Differentiating between ''Heilkunde'' which does not need to be approved by the BfS and ''medical research'' is whether the specific application of radiation (beam quality, dose, schedule, target volume, etc.) is a clinically established and recognized procedure. This must be answered by the qualified physician(s) (''fachkundiger Arzt'' according to German radiation protection law) in charge of the study and the treatments of the patients within the study, taking into consideration of the best available evidence from clinical studies, guidelines and consensus papers. Among the important parameters for assessment are indication, total dose, and fractionation. Radiation treatments applied outside clinical trials do not require approval by the BfS, even if they are applied within a randomized or nonrandomized clinical trial

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-rich foods, especially during certain stages of life when more iron is needed, such as ... to advancing science and translating discoveries into clinical practice to promote ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ... Cells From Iron-deficient Donors: Recovery and Storage Quality. Learn more about participating in a clinical trial . ...

  20. Improving data transparency in clinical trials using blockchain smart contracts [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Timothy Nugent

    2016-10-01

    Full Text Available The scientific credibility of findings from clinical trials can be undermined by a range of problems including missing data, endpoint switching, data dredging, and selective publication. Together, these issues have contributed to systematically distorted perceptions regarding the benefits and risks of treatments. While these issues have been well documented and widely discussed within the profession, legislative intervention has seen limited success. Recently, a method was described for using a blockchain to prove the existence of documents describing pre-specified endpoints in clinical trials. Here, we extend the idea by using smart contracts - code, and data, that resides at a specific address in a blockchain, and whose execution is cryptographically validated by the network - to demonstrate how trust in clinical trials can be enforced and data manipulation eliminated. We show that blockchain smart contracts provide a novel technological solution to the data manipulation problem, by acting as trusted administrators and providing an immutable record of trial history.

  1. 21 CFR 50.54 - Clinical investigations not otherwise approvable that present an opportunity to understand...

    Science.gov (United States)

    2010-04-01

    ... that present an opportunity to understand, prevent, or alleviate a serious problem affecting the health... opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children... clinical investigation presents a reasonable opportunity to further the understanding, prevention, or...

  2. Case Report: Clinically amyopathic dermatomyositis presenting acutely with isolated facial edema [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Efthymia Pappa

    2018-03-01

    Full Text Available A 45-year-old Asian man presented with acute-onset periorbital and facial edema associated with pyrexia. Muscle weakness was absent. Initial laboratory investigations showed an inflammatory reaction, while screening for infections was negative. Serum muscle enzyme levels were normal. He was hospitalized and treated empirically with antibiotics and corticosteroids, pending the result of facial skin and muscle biopsy. He showed a good clinical and laboratory response but an attempt to discontinue corticosteroids led to a prompt relapse of facial edema and pyrexia, associated with rising laboratory indices of inflammation. Biopsy findings were typical of dermatomyositis. Reintroduction of corticosteroid treatment resulted in complete clinical and laboratory remission. Facial edema as the sole clinical manifestation of dermatomyositis is extremely rare. There have been no previous reports of isolated facial edema in the setting of acute, clinically amyopathic dermatomyositis in adults. A high level of suspicion is required to make the diagnosis in the absence of myopathy and the hallmark cutaneous manifestations of the disease (heliotrope rash, Gottron papules.

  3. Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs.

    Science.gov (United States)

    Agrawal, Mukta; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G; Chougule, Mahavir Bhupal; Shoyele, Sunday A; Alexander, Amit

    2018-05-23

    According to the Alzheimer Association Report (2017), Alzheimer's disease (AD) is the 6th primary cause of death in the USA, which affects nearly 5.5 million people. In the year 2017 itself, the cost of AD treatment in the USA has been reported to rise to $259 billion. This statistic shows the severity of the disease in the USA which is very much similar across the globe. On the other hand, the treatment remains limited to a few conventional oral medications (approved by FDA). These are mainly acting superficially from mild to the moderate AD. The therapeutic efficacy of the drug is not only affected by its reduced concentration in the brain owing to the existence of blood-brain-barrier (BBB) but also due to its low brain permeability. In this context, the intranasal (IN) route of drug administration has emerged as an alternative route over the systemic (oral and parenteral) drug delivery to the brain. The delivery of the drug via an IN route offers various advantages over systemic drug delivery system, as it directly delivers the drug into the brain via olfactory route. Presence of drug in the olfactory bulb, in turn, increases the drug bioavailability in the brain and reduces the drug degradation as well as wastage of the drug through` systemic clearance. However, there is also some limitation associated with IN like poor drug permeation through the nasal mucosa and mucociliary clearance. The delivery system various through novel strategies (nano drug carrier system, colloidal carriers, mucoadhesive devices, controlled delivery system, pro-drug, etc.) are adapted to overcome the above-stated limitations. Although, after all, such successful research claims, very few of the nose-to-brain drug delivery of anti-AD drugs have gained market approval due to lack of sufficient clinical evidence. Onzetra Xsail® is one such marketed preparations approved for IN delivery used for the treatment of a brain disorder; migraine. In the field of patents also, no work is found

  4. Rapid assessment of iron in blood plasma and serum by spectrophotometry with cloud-point extraction [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Tatyana Samarina

    2015-08-01

    Full Text Available Rapid photometric assessment of iron in blood plasma and serum by a simple procedure after the extraction of iron(II complex with 1-nitroso-2-naphthol in the micellar phase of a nonionic surfactant at the cloud point upon heating (pH range is 4.5–6.3 is proposed. The procedure trueness was verified using a standard reference protocol using bathophenanthroline. The advantages of the procedure are higher sensitivity than the reference protocol: the limit of detection is 0.03 μg/mL, the limit of quantitation is 0.1 μg/mL, the determination range is 0.1 – 2.8 μg/mL (RSD 0.02–0.10. Copper does not interfere with the iron assessment.

  5. Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

    Science.gov (United States)

    2017-10-01

    US Food and Drug Administration Perspective.” Both manuscripts have been attached to annual report submitted to Department of Defenses in November...follow-up, conduct weekly telephone meetings with site data managers , and conduct monthly telephone meetings with site PIs (Months 23-75) Completed...Measurement in Cancer Clinical Trials: The US Food and Drug Administration Perspective. Cancer, 2014 Mar 1;120(5):761-7. doi: 10.1002/cncr.28470

  6. Improving data transparency in clinical trials using blockchain smart contracts [version 1; referees: 3 approved

    OpenAIRE

    Timothy Nugent; David Upton; Mihai Cimpoesu

    2016-01-01

    The scientific credibility of findings from clinical trials can be undermined by a range of problems including missing data, endpoint switching, data dredging, and selective publication. Together, these issues have contributed to systematically distorted perceptions regarding the benefits and risks of treatments. While these issues have been well documented and widely discussed within the profession, legislative intervention has seen limited success. Recently, a method was described for using...

  7. Iron deficiency

    DEFF Research Database (Denmark)

    Schou, Morten; Bosselmann, Helle; Gaborit, Freja

    2015-01-01

    BACKGROUND: Both iron deficiency (ID) and cardiovascular biomarkers are associated with a poor outcome in heart failure (HF). The relationship between different cardiovascular biomarkers and ID is unknown, and the true prevalence of ID in an outpatient HF clinic is probably overlooked. OBJECTIVES.......043). CONCLUSION: ID is frequent in an outpatient HF clinic. ID is not associated with cardiovascular biomarkers after adjustment for traditional confounders. Inflammation, but not neurohormonal activation is associated with ID in systolic HF. Further studies are needed to understand iron metabolism in elderly HF...

  8. Evaluation of liver fat in the presence of iron with MRI using T2* correction: a clinical approach.

    Science.gov (United States)

    Henninger, Benjamin; Benjamin, Henninger; Kremser, Christian; Christian, Kremser; Rauch, Stefan; Stefan, Rauch; Eder, Robert; Robert, Eder; Judmaier, Werner; Werner, Judmaier; Zoller, Heinz; Heinz, Zoller; Michaely, Henrik; Henrik, Michaely; Schocke, Michael; Michael, Schocke

    2013-06-01

    To assess magnetic resonance imaging (MRI) with conventional chemical shift-based sequences with and without T2* correction for the evaluation of steatosis hepatitis (SH) in the presence of iron. Thirty-one patients who underwent MRI and liver biopsy because of clinically suspected diffuse liver disease were retrospectively analysed. The signal intensity (SI) was calculated in co-localised regions of interest (ROIs) using conventional spoiled gradient-echo T1 FLASH in-phase and opposed-phase (IP/OP). T2* relaxation time was recorded in a fat-saturated multi-echo-gradient-echo sequence. The fat fraction (FF) was calculated with non-corrected and T2*-corrected SIs. Results were correlated with liver biopsy. There was significant difference (P T2* corrected FF in patients with SH and concomitant hepatic iron overload (HIO). Using 5 % as a threshold resulted in eight false negative results with uncorrected FF whereas T2* corrected FF lead to true positive results in 5/8 patients. ROC analysis calculated three threshold values (8.97 %, 5.3 % and 3.92 %) for T2* corrected FF with accuracy 84 %, sensitivity 83-91 % and specificity 63-88 %. FF with T2* correction is accurate for the diagnosis of hepatic fat in the presence of HIO. Findings of our study suggest the use of IP/OP imaging in combination with T2* correction. • Magnetic resonance helps quantify both iron and fat content within the liver • T2* correction helps to predict the correct diagnosis of steatosis hepatitis • "Fat fraction" from T2*-corrected chemical shift-based sequences accurately quantifies hepatic fat • "Fat fraction" without T2* correction underestimates hepatic fat with iron overload.

  9. A fast-track anaemia clinic in the Emergency Department: cost-analysis of intravenous iron administration for treating iron-deficiency anaemia.

    Science.gov (United States)

    Quintana-Díaz, Manuel; Muñoz-Romo, Raúl; Gómez-Ramírez, Susana; Pavía, José; Borobia, Alberto M; García-Erce, José A; Muñoz, Manuel

    2017-09-01

    A fast-track anaemia clinic (FTAC) for the management of moderate-to-severe iron-deficiency anaemia (IDA) was established in our Emergency Department in 2010. In this FTAC, the replacement of packed red cell transfusion by ferric carboxymaltose administration was proven to be safe and effective. The aim of this study was a cost-analysis of IDA management in the FTAC, comparing this management with the previous standard care pathway consisting of packed red cell transfusion, if needed, and referral to outpatient specialised care. A cost study was performed for patients with IDA who were at risk of requiring transfusion (haemoglobin costs in the FTAC were compared to those theoretically incurred if these patients had been managed using the standard care pathway. In addition, a sensitivity analysis considering variations of up to ±30% in ferric carboxymaltose and packed red cell acquisition costs was performed (49 possible scenarios). Between 2012 and 2015, 238 IDA patients were treated in the FTAC. The average treatment cost was € 594±337/patient in the FTAC group and € 672±301/patient in the standard care pathway group, with a saving of € 78±28/patient (95% CI, 22-133; pcosts in the FTAC (€ 480-722/patient), compared with those of the standard care pathway (€ 550-794/patient), resulted in significant cost-savings for all studied scenarios (€ 51-104/patient; pcost-saving compared with the standard care pathway.

  10. Genomic variant annotation workflow for clinical applications [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Thomas Thurnherr

    2016-10-01

    Full Text Available Annotation and interpretation of DNA aberrations identified through next-generation sequencing is becoming an increasingly important task. Even more so in the context of data analysis pipelines for medical applications, where genomic aberrations are associated with phenotypic and clinical features. Here we describe a workflow to identify potential gene targets in aberrated genes or pathways and their corresponding drugs. To this end, we provide the R/Bioconductor package rDGIdb, an R wrapper to query the drug-gene interaction database (DGIdb. DGIdb accumulates drug-gene interaction data from 15 different resources and allows filtering on different levels. The rDGIdb package makes these resources and tools available to R users. Moreover, rDGIdb queries can be automated through incorporation of the rDGIdb package into NGS sequencing pipelines.

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Cells From Iron-deficient Donors: Recovery and Storage Quality. Learn more about participating in a clinical trial . View all trials from ClinicalTrials.gov . Visit Children and Clinical Studies to hear experts, parents, and ...

  12. Methodological challenges for the evaluation of clinical effectiveness in the context of accelerated regulatory approval: an overview.

    Science.gov (United States)

    Woolacott, Nerys; Corbett, Mark; Jones-Diette, Julie; Hodgson, Robert

    2017-10-01

    Regulatory authorities are approving innovative therapies with limited evidence. Although this level of data is sufficient for the regulator to establish an acceptable risk-benefit balance, it is problematic for downstream health technology assessment, where assessment of cost-effectiveness requires reliable estimates of effectiveness relative to existing clinical practice. Some key issues associated with a limited evidence base include using data, from nonrandomized studies, from small single-arm trials, or from single-center trials; and using surrogate end points. We examined these methodological challenges through a pragmatic review of the available literature. Methods to adjust nonrandomized studies for confounding are imperfect. The relative treatment effect generated from single-arm trials is uncertain and may be optimistic. Single-center trial results may not be generalizable. Surrogate end points, on average, overestimate treatment effects. Current methods for analyzing such data are limited, and effectiveness claims based on these suboptimal forms of evidence are likely to be subject to significant uncertainty. Assessments of cost-effectiveness, based on the modeling of such data, are likely to be subject to considerable uncertainty. This uncertainty must not be underestimated by decision makers: methods for its quantification are required and schemes to protect payers from the cost of uncertainty should be implemented. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  13. Studies on the pathogenesis in iron deficiency anemia Part 1. Urinary iron excretion in iron deficiency anemia patients and rats in various iron states

    OpenAIRE

    中西,徳彦

    1991-01-01

    In the "iron excretion test" , urinary iron excretion after injection of saccharated iron oxide has been reported to be accelerated in relapsing idiopathic iron deficiency anemia. To determine the relevance of urinary iron excretion to clinical factors other than iron metabolism, 15 clinical parameters were evaluated. The serum creatinine level was positively and the serum albumin level was negatively correlated with urinary iron excretion, showing coefficients of r=0.97,-0.86 respectively, a...

  14. Liver iron concentration quantification by MRI: are recommended protocols accurate enough for clinical practice?

    International Nuclear Information System (INIS)

    Castiella, Agustin; Zapata, Eva Mia; Alustiza, Jose M.; Emparanza, Jose I.; Costero, Belen; Diez, Maria I.

    2011-01-01

    To assess the accuracy of quantification of liver iron concentration (LIC) by MRI using the Rennes University (URennes) algorithm. In the overall study period 1999-2006 the LIC in 171 patients was calculated with the URennes model and the results were compared with LIC measured by liver biopsy. The biopsy showed that 107 patients had no overload, 38 moderate overload and 26 high overload. The correlation between MRI and biopsy was r = 0.86. MRI correctly classified 105 patients according to the various levels of LIC. Diagnostic accuracy was 61.4%, with a tendency to overestimate overload: 43% of patients with no overload were diagnosed as having overload, and 44.7% of patients with moderate overload were diagnosed as having high overload. The sensitivity of the URennes method for high overload was 92.3%, and the specificity for the absence of overload was 57.0%. MRI values greater than 170 μmol Fe/g revealed a positive predictive value (PPV) for haemochromatosis of 100% (n = 18); concentrations below 60 μmol Fe/g had a negative predictive value (NPV) of 100% for haemochromatosis (n = 101). The diagnosis in 44 patients with intermediate values remained uncertain. The assessment of LIC with the URennes method was useful in 74.3% of the patients to rule out or to diagnose high iron overload. The method has a tendency to overestimate overload, which limits its diagnostic performance. (orig.)

  15. Liver iron concentration quantification by MRI: are recommended protocols accurate enough for clinical practice?

    Energy Technology Data Exchange (ETDEWEB)

    Castiella, Agustin; Zapata, Eva M. [Mendaro Hospital, Gastroenterology Service, Mendaro (Spain); Alustiza, Jose M. [Osatek Donostia, Radiology Service, Donostia (Spain); Emparanza, Jose I. [Donostia Hospital CASPe, CIBER-ESP, Clinical Epidemiology Unit, Donostia (Spain); Costero, Belen [Principe de Asturias Hospital, Gastroenterology Service, Alcala de Henares (Spain); Diez, Maria I. [Principe de Asturias Hospital, Radiology Service, Alcala de Henares (Spain)

    2011-01-15

    To assess the accuracy of quantification of liver iron concentration (LIC) by MRI using the Rennes University (URennes) algorithm. In the overall study period 1999-2006 the LIC in 171 patients was calculated with the URennes model and the results were compared with LIC measured by liver biopsy. The biopsy showed that 107 patients had no overload, 38 moderate overload and 26 high overload. The correlation between MRI and biopsy was r = 0.86. MRI correctly classified 105 patients according to the various levels of LIC. Diagnostic accuracy was 61.4%, with a tendency to overestimate overload: 43% of patients with no overload were diagnosed as having overload, and 44.7% of patients with moderate overload were diagnosed as having high overload. The sensitivity of the URennes method for high overload was 92.3%, and the specificity for the absence of overload was 57.0%. MRI values greater than 170 {mu}mol Fe/g revealed a positive predictive value (PPV) for haemochromatosis of 100% (n = 18); concentrations below 60 {mu}mol Fe/g had a negative predictive value (NPV) of 100% for haemochromatosis (n = 101). The diagnosis in 44 patients with intermediate values remained uncertain. The assessment of LIC with the URennes method was useful in 74.3% of the patients to rule out or to diagnose high iron overload. The method has a tendency to overestimate overload, which limits its diagnostic performance. (orig.)

  16. Individuality, phenotypic differentiation, dormancy and ‘persistence’ in culturable bacterial systems: commonalities shared by environmental, laboratory, and clinical microbiology [version 2; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Douglas Kell

    2015-09-01

    Full Text Available For bacteria, replication mainly involves growth by binary fission. However, in a very great many natural environments there are examples of phenotypically dormant, non-growing cells that do not replicate immediately and that are phenotypically ‘nonculturable’ on media that normally admit their growth. They thereby evade detection by conventional culture-based methods. Such dormant cells may also be observed in laboratory cultures and in clinical microbiology. They are usually more tolerant to stresses such as antibiotics, and in clinical microbiology they are typically referred to as ‘persisters’. Bacterial cultures necessarily share a great deal of relatedness, and inclusive fitness theory implies that there are conceptual evolutionary advantages in trading a variation in growth rate against its mean, equivalent to hedging one’s bets. There is much evidence that bacteria exploit this strategy widely. We here bring together data that show the commonality of these phenomena across environmental, laboratory and clinical microbiology. Considerable evidence, using methods similar to those common in environmental microbiology, now suggests that many supposedly non-communicable, chronic and inflammatory diseases are exacerbated (if not indeed largely caused by the presence of dormant or persistent bacteria (the ability of whose components to cause inflammation is well known. This dormancy (and resuscitation therefrom often reflects the extent of the availability of free iron. Together, these phenomena can provide a ready explanation for the continuing inflammation common to such chronic diseases and its correlation with iron dysregulation. This implies that measures designed to assess and to inhibit or remove such organisms (or their access to iron might be of much therapeutic benefit.

  17. Evidence for the Influence of the Iron Regulatory MHC Class I Molecule HFE on Tumor Progression in Experimental Models and Clinical Populations

    Science.gov (United States)

    Weston, Cody; Connor, James

    2014-01-01

    Proteins involved in iron regulation are modifiers of cancer risk and progression. Of these, the HFE protein (high iron gene and its protein product) is of particular interest because of its interaction with both iron handling and immune function and the high rate of genetic polymorphisms resulting in a mutant protein. Clinical studies suggest that HFE polymorphisms increase the risk of certain cancers, but the inconsistent outcomes suggest a more nuanced effect, possibly interacting with other genetic or environmental factors. Some basic science research has been conducted to begin to understand the implications of variant HFE genotype on cancer, but the story is far from complete. In particular, putative mechanisms exist for HFE to affect tumor progression through its role in iron handling and its major histocompatibility complex class I structural features. In this review, the current understanding of the role of HFE in cancer is described and models for future directions are identified. PMID:25520556

  18. Clinical and economic burden of infused iron chelation therapy in the United States.

    Science.gov (United States)

    Payne, Krista A; Desrosiers, Marie-Pierre; Caro, J Jaime; Baladi, Jean-François; Lordan, Noreen; Proskorovsky, Irina; Ishak, Khajak; Rofail, Diana

    2007-10-01

    Patients requiring chronic blood transfusions are at risk for iron overload, which, if not treated by iron chelation therapy (ICT), can create serious organ damage and reduce life expectancy. Current ICT requires burdensome 8- to 12-hour infusions five to seven times per week. A naturalistic study of the burden of infused ICT was conducted in four US centers. Data from the initial and most recent years of ICT were collected from medical charts of consenting thalassemia (n = 40) and sickle cell disease (n = 9) patients. Quality of life (QoL), treatment satisfaction, and ICT-related resource utilization data were also collected from a patient interview. Mean serum ferritin levels during the initial (2519 +/- 1382 ng/mL) and most recent (2741 +/- 2532 ng/mL) years remained unacceptably high and increased over time (306 +/- 2200 ng/mL; mean of 20+/- years of therapy). Within 30 days before interview, 55 percent of patients suffered at least one ICT-related adverse event; 76 percent missed at least one dose. QoL, measured by the SF-36, and treatment satisfaction appear compromised in this cohort. Although total annual costs of ICT were estimated at USD $30,000 to $35,000, drug accounted for only 50 to 60 percent of this amount. Infused ICT may not provide adequate effectiveness in the real world. High ferritin levels seem to be associated with ICT noncompliance, likely in relation to the bothersome mode of administration and side effects. The total cost of ICT appears to well exceed that of drug alone.

  19. Clinical features and dysfunctions of iron metabolism in Parkinson disease patients with hyper echogenicity in substantia nigra: a cross-sectional study.

    Science.gov (United States)

    Yu, Shu-Yang; Cao, Chen-Jie; Zuo, Li-Jun; Chen, Ze-Jie; Lian, Teng-Hong; Wang, Fang; Hu, Yang; Piao, Ying-Shan; Li, Li-Xia; Guo, Peng; Liu, Li; Yu, Qiu-Jin; Wang, Rui-Dan; Chan, Piu; Chen, Sheng-di; Wang, Xiao-Min; Zhang, Wei

    2018-01-17

    Transcranial ultrasound is a useful tool for providing the evidences for the early diagnosis and differential diagnosis of Parkinson disease (PD). However, the relationship between hyper echogenicity in substantia nigra (SN) and clinical symptoms of PD patients remains unknown, and the role of dysfunction of iron metabolism on the pathogenesis of SN hyper echogenicity is unclear. PD patients was detected by transcranial sonography and divided into with no hyper echogenicity (PDSN-) group and with hyper echogenicity (PDSN+) group. Motor symptoms (MS) and non-motor symptoms (NMS) were evaluated, and the levels of iron and related proteins in serum and cerebrospinal fluid (CSF) were detected for PD patients. Data comparison between the two groups and correlation analyses were performed. PDSN+ group was significantly older, and had significantly older age of onset, more advanced Hohen-Yahr stage, higher SCOPA-AUT score and lower MoCA score than PDSN- group (P hyper echogenicity in SN are older, at more advanced disease stage, have severer motor symptoms, and non-motor symptoms of cognitive impairment and autonomic dysfunction. Hyper echogenicity of SN in PD patients is related to dysfunction of iron metabolism, involving increased iron transport from peripheral system to central nervous system, reduction of intracellular iron release and excessive iron deposition in brain.

  20. Changes in serum markers of iron metabolism and their clinical significance in patients with nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    OU Qiang

    2016-12-01

    Full Text Available ObjectiveTo investigate the changes in the serum markers of iron metabolism and their clinical significance in patients with nonalcoholic fatty liver disease (NAFLD. MethodsA total of 68 NAFLD patients who were admitted to The Eighth People′s Hospital of Shanghai from July 2014 to April 2016 were enrolled as NAFLD group, and 70 healthy persons who underwent physical examination were enrolled as healthy control group. Among the 68 patients in the NAFLD group, 24 had NAFLD alone and 44 were complicated by abnormal alanine aminotransferase (ALT level. The levels of aspartate aminotransferase (AST, ALT, total cholesterol (TC, triglyceride (TG, and serum markers of iron metabolism [serum iron (SI, serum ferritin (SF, and serum hepcidin (HEPC] were measured for all patients, and the correlations between abnormal ALT level and serum markers of iron metabolism were analyzed. The independent samples t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, and the Pearson correlation coefficient was used to investigate the correlation between two variables. ResultsThe NAFLD group had significantly higher body mass index and serum levels of ALT, AST, TC, and TG than the healthy control group (t=9.8, 8.6, 8.5, 9.2, and 2.7, all P<0.05. Compared with the healthy control group, the NAFLD group had significantly higher levels of SI (21.7±7.1 μmol/L vs 187±6.9 μmol/L, t=2.3, P=0.02 and SF (340.2±257.6 μg/L vs 119.1±81.2 μg/L, t=6.7, P<0.01 and a significantly lower level of HEPC (12.2±5.3 μg/L vs 22.2±6.5 μg/L, t=9.9, P<0.01. Compared with those with NAFLD alone, the patients complicated by abnormal ALT level had significantly higher serum levels of ALT (89±58 U/L vs 26±8 U/L, t=7.1, P<0.01, SI (23.4±6.2 μmol/L vs 19.6±7.9 μmol/L, t=2.2, P=0.03, and SF (406.2±290.0 μg/L vs 219.4±112.0 μg/L, t=3.7, P<0.01, as well as a significantly

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron supplements work best to treat iron-deficiency anemia in children who do not consume the daily recommended amount ... and Clinical Studies to hear experts, parents, and children talk about their experiences with clinical ... Anemia Arrhythmia Blood Donation Blood Tests Blood ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... how we are using current research and advancing research to prevent iron-deficiency anemia. Participate in NHLBI Clinical Trials will explain our ongoing clinical studies that are investigating prevention strategies for iron-deficiency anemia. Signs, Symptoms, and Complications ...

  3. Clinical efficacy and safety evaluation of tailoring iron chelation practice in thalassaemia patients from Asia-Pacific: a subanalysis of the EPIC study of deferasirox.

    Science.gov (United States)

    Viprakasit, Vip; Ibrahim, Hishamshah; Ha, Shau-Yin; Ho, Phoebe Joy; Li, Chi-Kong; Chan, Lee-Lee; Chiu, Chang-Fang; Sutcharitchan, Pranee; Habr, Dany; Domokos, Gabor; Roubert, Bernard; Xue, Hong-Ling; Bowden, Donald K; Lin, Kai-Hsin

    2011-03-01

    Although thalassaemia is highly prevalent in the Asia-Pacific region, clinical data on efficacy and safety profiles of deferasirox in patients from this region are rather limited. Recently, data from the multicentre Evaluation of Patients' Iron Chelation with Exjade (EPIC) study in 1744 patients with different anaemias has provided an opportunity to analyse 1115 thalassaemia patients, of whom 444 patients were from five countries in the Asia-Pacific region (AP) for whom thalassaemia management and choice of iron chelators were similar. Compared to the rest of the world (ROW), baseline clinical data showed that the AP group appeared to be more loaded with iron (3745.0 vs. 2822.0 ng/ml) and had a higher proportion on deferoxamine monotherapy prior to the study (82.9 vs. 58.9%). Using a starting deferasirox dose based on transfusional iron intake and tailoring it to individual patient response, clinical efficacy based on serum ferritin reduction in AP and ROW thalassaemia patients was similar. Interestingly, the AP group developed a higher incidence of drug-related skin rash compared to ROW (18.0 vs. 7.2%), which may indicate different pharmacogenetic backgrounds in the two populations. Our analysis confirms that, with appropriate adjustment of dose, deferasirox can be clinically effective across different regions, with manageable side effects.

  4. Current understanding of iron homeostasis.

    Science.gov (United States)

    Anderson, Gregory J; Frazer, David M

    2017-12-01

    Iron is an essential trace element, but it is also toxic in excess, and thus mammals have developed elegant mechanisms for keeping both cellular and whole-body iron concentrations within the optimal physiologic range. In the diet, iron is either sequestered within heme or in various nonheme forms. Although the absorption of heme iron is poorly understood, nonheme iron is transported across the apical membrane of the intestinal enterocyte by divalent metal-ion transporter 1 (DMT1) and is exported into the circulation via ferroportin 1 (FPN1). Newly absorbed iron binds to plasma transferrin and is distributed around the body to sites of utilization with the erythroid marrow having particularly high iron requirements. Iron-loaded transferrin binds to transferrin receptor 1 on the surface of most body cells, and after endocytosis of the complex, iron enters the cytoplasm via DMT1 in the endosomal membrane. This iron can be used for metabolic functions, stored within cytosolic ferritin, or exported from the cell via FPN1. Cellular iron concentrations are modulated by the iron regulatory proteins (IRPs) IRP1 and IRP2. At the whole-body level, dietary iron absorption and iron export from the tissues into the plasma are regulated by the liver-derived peptide hepcidin. When tissue iron demands are high, hepcidin concentrations are low and vice versa. Too little or too much iron can have important clinical consequences. Most iron deficiency reflects an inadequate supply of iron in the diet, whereas iron excess is usually associated with hereditary disorders. These disorders include various forms of hemochromatosis, which are characterized by inadequate hepcidin production and, thus, increased dietary iron intake, and iron-loading anemias whereby both increased iron absorption and transfusion therapy contribute to the iron overload. Despite major recent advances, much remains to be learned about iron physiology and pathophysiology. © 2017 American Society for Nutrition.

  5. The iron chelator deferasirox protects mice from mucormycosis through iron starvation

    Science.gov (United States)

    Ibrahim, Ashraf S.; Gebermariam, Teclegiorgis; Fu, Yue; Lin,, Lin; Husseiny, Mohamed I.; French, Samuel W.; Schwartz, Julie; Skory, Christopher D.; Edwards, John E.; Spellberg, Brad J.

    2007-01-01

    Mucormycosis causes mortality in at least 50% of cases despite current first-line therapies. Clinical and animal data indicate that the presence of elevated available serum iron predisposes the host to mucormycosis. Here we demonstrate that deferasirox, an iron chelator recently approved for use in humans by the US FDA, is a highly effective treatment for mucormycosis. Deferasirox effectively chelated iron from Rhizopus oryzae and demonstrated cidal activity in vitro against 28 of 29 clinical isolates of Mucorales at concentrations well below clinically achievable serum levels. When administered to diabetic ketoacidotic or neutropenic mice with mucormycosis, deferasirox significantly improved survival and decreased tissue fungal burden, with an efficacy similar to that of liposomal amphotericin B. Deferasirox treatment also enhanced the host inflammatory response to mucormycosis. Most importantly, deferasirox synergistically improved survival and reduced tissue fungal burden when combined with liposomal amphotericin B. These data support clinical investigation of adjunctive deferasirox therapy to improve the poor outcomes of mucormycosis with current therapy. As iron availability is integral to the pathogenesis of other infections (e.g., tuberculosis, malaria), broader investigation of deferasirox as an antiinfective treatment is warranted. PMID:17786247

  6. Clinical evaluation of multishot echo planar imaging after administration of superparamagnetic iron oxide for hepatic tumors

    International Nuclear Information System (INIS)

    Sugai, Yukio; Watanabe, Yorihisa; Ito, Kazushi; Hosoya, Takaaki; Yamaguchi, Koichi

    1998-01-01

    Ten cases of hepatocellular carcinoma and three cases of metastatic liver tumor were evaluated using breath-hold multishot echo planar imaging (EPI) before and after administration of super-paramagnetic iron oxide (SPIO), and the results were compared to those with breath-hold fast multi-planar SPGR (T 1 WI) and fat-suppressed respiratory-triggered FSE (T 2 WI). Qualitative imaging evaluation of lesion detectability showed that T 2 WI was much more useful than T 1 WI as previously reported, and more useful than EPI. Quantitative evaluation showed that the signal to noise (S/N) ratios of the liver parenchyma decreased after administration of SPIO and the changes were significant on all pulse sequences. The change ratio of the S/N ratio of the liver parenchyma after administration of SPIO on EPI was significantly higher than on T 1 WI and T 2 WI. The tumor-liver contrast to noise (C/N) ratios increased after administration of SPIO and the changes were significant on T 1 WI and T 2 WI, but not on EPI. These results suggested that the tumor S/N ratio decreased after administration of SPIO on EPI. The tumor diameters on EPI were significantly reduced after administration of SPIO. Magnetization and flow artifacts on EPI were detected in all cases and caused distortion: the signal decreased in the liver parenchyma. We concluded that EPI after administration of SPIO is not currently useful compared to other pulse sequences and cannot yet replace T 2 WI. (author)

  7. Iron deficiency intravenous substitution in a Swiss academic primary care division: analysis of practices

    Directory of Open Access Journals (Sweden)

    Varcher M

    2016-07-01

    Full Text Available Monica Varcher,1 Sofia Zisimopoulou,1 Olivia Braillard,1 Bernard Favrat,2 Noëlle Junod Perron1 1Department of Community, Primary and Emergency Care, Division of Primary Care, Geneva University Hospitals, Geneva, 2Department of Ambulatory Care and Community Medicine, University of Lausanne, Lausanne, Switzerland Background: Iron deficiency is a common problem in primary care and is usually treated with oral iron substitution. With the recent simplification of intravenous (IV iron administration (ferric carboxymaltose and its approval in many countries for iron deficiency, physicians may be inclined to overutilize it as a first-line substitution.Objective: The aim of this study was to evaluate iron deficiency management and substitution practices in an academic primary care division 5 years after ferric carboxymaltose was approved for treatment of iron deficiency in Switzerland.Methods: All patients treated for iron deficiency during March and April 2012 at the Geneva University Division of Primary Care were identified. Their medical files were analyzed for information, including initial ferritin value, reasons for the investigation of iron levels, suspected etiology, type of treatment initiated, and clinical and biological follow-up. Findings were assessed using an algorithm for iron deficiency management based on a literature review.Results: Out of 1,671 patients, 93 were treated for iron deficiency. Median patients’ age was 40 years and 92.5% (n=86 were female. The average ferritin value was 17.2 μg/L (standard deviation 13.3 μg/L. The reasons for the investigation of iron levels were documented in 82% and the suspected etiology for iron deficiency was reported in 67%. Seventy percent of the patients received oral treatment, 14% IV treatment, and 16% both. The reasons for IV treatment as first- and second-line treatment were reported in 57% and 95%, respectively. Clinical and biological follow-up was planned in less than two-thirds of the

  8. Classification of processes involved in sharing individual participant data from clinical trials [version 1; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Christian Ohmann

    2018-02-01

    Full Text Available Background: In recent years, a cultural change in the handling of data from research has resulted in the strong promotion of a culture of openness and increased sharing of data. In the area of clinical trials, sharing of individual participant data involves a complex set of processes and the interaction of many actors and actions. Individual services/tools to support data sharing are available, but what is missing is a detailed, structured and comprehensive list of processes/subprocesses involved and tools/services needed. Methods: Principles and recommendations from a published data sharing consensus document are analysed in detail by a small expert group. Processes/subprocesses involved in data sharing are identified and linked to actors and possible services/tools. Definitions are adapted from the business process model and notation (BPMN and applied in the analysis. Results: A detailed and comprehensive list of individual processes/subprocesses involved in data sharing, structured according to 9 main processes, is provided. Possible tools/services to support these processes/subprocesses are identified and grouped according to major type of support. Conclusions: The list of individual processes/subprocesses and tools/services identified is a first step towards development of a generic framework or architecture for sharing of data from clinical trials. Such a framework is strongly needed to give an overview of how various actors, research processes and services could form an interoperable system for data sharing.

  9. Classification of processes involved in sharing individual participant data from clinical trials [version 2; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Christian Ohmann

    2018-04-01

    Full Text Available Background: In recent years, a cultural change in the handling of research data has resulted in the promotion of a culture of openness and an increased sharing of data. In the area of clinical trials, sharing of individual participant data involves a complex set of processes and the interaction of many actors and actions. Individual services and tools to support data sharing are becoming available, but what is missing is a detailed, structured and comprehensive list of processes and subprocesses involved and the tools and services needed. Methods: Principles and recommendations from a published consensus document on data sharing were analysed in detail by a small expert group. Processes and subprocesses involved in data sharing were identified and linked to actors and possible supporting services and tools. Definitions adapted from the business process model and notation (BPMN were applied in the analysis. Results: A detailed and comprehensive tabulation of individual processes and subprocesses involved in data sharing, structured according to 9 main processes, is provided. Possible tools and services to support these processes are identified and grouped according to the major type of support. Conclusions: The identification of the individual processes and subprocesses and supporting tools and services, is a first step towards development of a generic framework or architecture for the sharing of data from clinical trials. Such a framework is needed to provide an overview of how the various actors, research processes and services could interact to form a sustainable system for data sharing.

  10. Adult attention-deficit/hyperactivity disorder: Associations between subtype and lifetime substance use – a clinical study. [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Michael Liebrenz

    2015-07-01

    Full Text Available ADHD is the one of the most prevalent childhood disorders and has been associated with impairments persisting into adulthood. Specifically, childhood ADHD is an independent clinical risk factor for the development of later substance use disorders (SUD. Moreover, adults who meet diagnostic criteria for ADHD have shown high rates of comorbid SUDs. Few studies, however, have reported on the relationship between ADHD subtypes and SUD in adult samples. The purpose of this study was to characterize a clinical sample of adults with ADHD and to identify possible associations between ADHD subtypes, lifetime substance use, and if ADHD subtypes may be preferentially associated with specific substances of abuse. We recruited 413 adult ADHD patients, performed an evaluation of their ADHD and conducted an interview on their use of psychotropic substances. Complete data was obtained for 349 patients. Lifetime substance abuse or dependence was 26% and occasional use was 57% in this sample. The inattentive subtype was significantly less likely to abuse or be dependent on cocaine than the combined subtype. Our findings underscore the high rate of comorbidity between substance use and ADHD in adults. The more frequent abuse/dependence of cocaine by adult patients with hyperactive-impulsive symptoms should be kept in mind when treating this patient group.

  11. Utilization of folic acid and iron supplementation services by pregnant women attending an antenatal clinic at a regional referral hospital in Kenya.

    Science.gov (United States)

    Maina-Gathigi, L; Omolo, J; Wanzala, P; Lindan, C; Makokha, A

    2013-09-01

    To determine utilization of iron and folic acid supplementation services among pregnant women in Kenya. A cross sectional study was conducted at Nyeri Hospital, a regional referral hospital in central Kenya. Women attending the antenatal clinic were selected through systematic sampling. A semi-structured questionnaire was administered to collect information on utilization of folic acid and iron supplementation services. Women who ingested folic acid or iron supplements for >4 days in a week were considered "highly compliant". The health worker in-charge of the antenatal clinic was interviewed about the frequency of supplement stock-outs during the past year. Haemoglobin concentration was measured directly from one drop of capillary blood and measured using portable HEMOCUE B-Hb photometer. Of the 381 women interviewed, only 23.6 % obtained antenatal care in the first trimester; 69.3 and 51.2 % received folic acid and iron supplements, respectively. However, only half (45-58 %) received any information about supplementation. Most women were initiated on folic acid (80.7 %) or iron (67.7 %) after 12 and 16 weeks of gestation, respectively, well after the recommended time period. However, more than 80 % of those who received folic acid and iron were highly compliant. Stock-outs were common at the facility. Of 361 women tested for Hb level, the prevalence of anaemia (Hb levels importance of supplements to pregnant women. Women who come late to antenatal clinic miss opportunities to start supplementation early in pregnancy. Problems with supply chain management exacerbate the problem.

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... red blood cells, called hemolysis . Hemolysis, in this case, is caused by strong muscle contractions and the ... to prevent iron-deficiency anemia. Participate in NHLBI Clinical Trials will explain our ongoing clinical studies that ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in ... Visit Children and Clinical Studies to hear experts, parents, and children talk about their experiences with clinical ...

  14. Clinical trial transparency update: an assessment of the disclosure of results of company-sponsored trials associated with new medicines approved in Europe in 2014.

    Science.gov (United States)

    Deane, Bryan R; Porkess, Sheuli

    2018-07-01

    The objective of this study was to assess the timely disclosure of results of company-sponsored clinical trials related to all new medicines approved by the European Medicines Agency (EMA) during 2014. This is the final extension of three previously reported studies of trials related to all new medicines approved in Europe in 2009, 2010 and 2011, and in 2012 and 2013. The original study found that over a three-year period over three-quarters of all trials were disclosed within 12 months and almost 90% were disclosed by the end of the study (31 January 2013). The extension studies (2012 and 2013 approvals) both showed an improvement in results disclosure within 12 months to 90%, and an overall disclosure rate of 92% and 93% respectively by the end of the studies. The methodology used was exactly as previously reported. Various publicly available information sources were searched for both clinical trial registration and disclosure of results. All completed company-sponsored trials related to each new medicine approved for marketing by the EMA in 2014, carried out in patients and recorded on a clinical trials registry and/or included in an EMA European Public Assessment Report (EPAR), were included. Information sources were searched between 1 May and 31 July 2016. The main outcome measure was the proportion of trials for which results had been disclosed on a registry or in the scientific literature either within 12 months of the later of either first regulatory approval or trial completion, or by 31 July 2016 (end of survey). Of the completed trials associated with 32 new medicines licensed to 22 different companies in 2014, results of 93% (505/542) had been disclosed within 12 months, and results of 96% (518/542) had been disclosed by 31 July 2016. The disclosure rate within 12 months of 93% suggests that industry is continuing to achieve disclosure in a timely manner. The overall disclosure rate at study end of 96% indicates that the improvement in transparency

  15. Case Report: A case report highlighting bilateral EDB wasting as a clinical marker for lumbar canal stenosis [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Bijoy Mohan Kumar

    2015-08-01

    Full Text Available Herein we discuss a case of a 55 year old male presenting with history suggestive of sciatica on the left leg. Straight leg raising (SLR test was positive at 45 degrees on the left side. His ankle reflex was absent and the power of extensor hallusus longus (EHL was 4/5 on the same side. MRI lumbosacral spine revealed left paramedian disc prolapsed on L4/L5 level with spinal canal diameter of 9mm.However since his bilateral extensor digitorm brevis (EDB were wasted, we suspected associated lumbar canal stenosis and thereby opted for laminectomy and discectomy in this case. Intraoperatively dural wasting, hypertrophied facets and narrow canal were confirmed. Laminectomy, medial facectectomy and discectomy were carried out. The patient recovered uneventfully with resolution of his sciatica-like pain. Bilateral EDB wasting thereby provides a clinical clue to the underlying lumbar canal stenosis and can help in making correct therapeutic decisions.

  16. Iron absorption studies

    International Nuclear Information System (INIS)

    Ekenved, G.

    1976-01-01

    The main objective of the present work was to study iron absorption from different iron preparations in different types of subjects and under varying therapeutic conditions. The studies were performed with different radioiron isotope techniques and with a serum iron technique. The preparations used were solutions of ferrous sulphate and rapidly-disintegrating tablets containing ferrous sulphate, ferrous fumarate and ferrous carbonate and a slow-release ferrous sulphate tablet of an insoluble matrix type (Duroferon Durules). The serum iron method was evaluated and good correlation was found between the serum iron response and the total amount of iron absorbed after an oral dose of iron given in solution or in tablet form. New technique for studying the in-vivo release properties of tablets was presented. Iron tablets labelled with a radio-isotope were given to healthy subjects. The decline of the radioactivity in the tablets was followed by a profile scanning technique applied to different types of iron tablets. The release of iron from the two types of tablets was shown to be slower in vivo than in vitro. It was found that co-administration of antacids and iron tablets led to a marked reduction in the iron absorption and that these drugs should not be administered sumultaneously. A standardized meal markedly decreased the absorbability of iron from iron tablets. The influence of the meal was more marked with rapidly-disintegrating than with slow-release ferrous sulphate tablets. The absorption from rapidly-disintegrating and slow-release ferrous sulphate tablets was compared under practical clinical conditions during an extended treatment period. The studies were performed in healthy subjects, blood donors and patients with iron deficiency anaemia and it was found that the absorption of iron from the slow-release tablets was significantly better than from the rapidly-disintegrating tablets in all three groups of subjects. (author)

  17. Premature Discontinuation of Prospective Clinical Studies Approved by a Research Ethics Committee - A Comparison of Randomised and Non-Randomised Studies.

    Directory of Open Access Journals (Sweden)

    Anette Blümle

    Full Text Available Premature discontinuation of clinical studies affects about 25% of randomised controlled trials (RCTs which raises concerns about waste of scarce resources for research. The risk of discontinuation of non-randomised prospective studies (NPSs is yet unclear.To compare the proportion of discontinued studies between NPSs and RCTs that received ethical approval.We systematically surveyed prospective longitudinal clinical studies that were approved by a single REC in Freiburg, Germany between 2000 and 2002. We collected study characteristics, identified subsequent publications, and surveyed investigators to elucidate whether a study was discontinued and, if so, why.Of 917 approved studies, 547 were prospective longitudinal studies (306 RCTs and 241 NPSs. NPSs were on average smaller than RCTs, more frequently single centre and pilot studies, and less frequently funded by industry. NPSs were less frequently discontinued than RCTs: 32/221 (14% versus 78/288 (27%, p<0.001, missing data excluded. Poor recruitment was the most frequent reason for discontinuation in both NPSs (36% and RCTs (37%.Compared to RCTs, NPSs were at lower risk for discontinuation. Measures to reliably predict, sustain, and stimulate recruitment could prevent discontinuation of many RCTs but also of some NPSs.

  18. Case Report: Diagnosis of hypogeusia after oral exposure to commercial cleaning agent and considerations for clinical taste testing [version 2; referees: 2 approved, 1 not approved

    Directory of Open Access Journals (Sweden)

    Marie Jetté

    2017-06-01

    Full Text Available Few reports in the literature document acute taste disturbance following exposure to toxic chemicals. We describe the case of a 54-year-old man who presented with primary complaint of tongue numbness and persistent problems with taste 1.5 years following oral exposure to a commercial cleaning agent. A test of olfaction revealed normosmia for age and gender. Lingual tactile two-point discrimination testing showed reduced somatosensation. Taste threshold testing using a 3-drop method demonstrated severe hypogeusia, though the patient was able to discriminate tastants at lower concentrations with a whole mouth swish and spit test. We conclude that clinical evaluation of dysgeusia can be performed using a number of previously published testing methods, however, determining causative factors may be confounded by duration since exposure, lack of knowledge of baseline taste function, and medications. Although many testing options exist, basic taste testing can be performed with minimal expertise or specialized equipment, depending on the patient history and goals of evaluation.

  19. Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic.

    Science.gov (United States)

    Meyskens, Frank L; Curt, Gregory A; Brenner, Dean E; Gordon, Gary; Herberman, Ronald B; Finn, Olivera; Kelloff, Gary J; Khleif, Samir N; Sigman, Caroline C; Szabo, Eva

    2011-03-01

    This article endeavors to clarify the current requirements and status of regulatory approval for chemoprevention (risk reduction) drugs and discusses possible improvements to the regulatory pathway for chemoprevention. Covering a wide range of topics in as much depth as space allows, this report is written in a style to facilitate the understanding of nonscientists and to serve as a framework for informing the directions of experts engaged more deeply with this issue. Key topics we cover here are as follows: a history of definitive cancer chemoprevention trials and their influence on the evolution of regulatory assessments; a brief review of the long-standing success of pharmacologic risk reduction of cardiovascular diseases and its relevance to approval for cancer risk reduction drugs; the use and limitations of biomarkers for developing and the approval of cancer risk reduction drugs; the identification of individuals at a high(er) risk for cancer and who are appropriate candidates for risk reduction drugs; business models that should incentivize pharmaceutical industry investment in cancer risk reduction; a summary of scientific and institutional barriers to development of cancer risk reduction drugs; and a summary of major recommendations that should help facilitate the pathway to regulatory approval for pharmacologic cancer risk reduction drugs.

  20. Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012

    Science.gov (United States)

    Miller, Jennifer E; Korn, David; Ross, Joseph S

    2015-01-01

    Objective To evaluate clinical trial registration, reporting and publication rates for new drugs by: (1) legal requirements and (2) the ethical standard that all human subjects research should be publicly accessible to contribute to generalisable knowledge. Design Cross-sectional analysis of all clinical trials submitted to the Food and Drug Administration (FDA) for drugs approved in 2012, sponsored by large biopharmaceutical companies. Data sources Information from Drugs@FDA, ClinicalTrials.gov, MEDLINE-indexed journals and drug company communications. Main outcome measures Clinical trial registration and results reporting in ClinicalTrials.gov, publication in the medical literature, and compliance with the 2007 FDA Amendments Acts (FDAAA), analysed on the drug level. Results The FDA approved 15 drugs sponsored by 10 large companies in 2012. We identified 318 relevant trials involving 99 599 research participants. Per drug, a median of 57% (IQR 32–83%) of trials were registered, 20% (IQR 12–28%) reported results in ClinicalTrials.gov, 56% (IQR 41–83%) were published, and 65% (IQR 41–83%) were either published or reported results. Almost half of all reviewed drugs had at least one undisclosed phase II or III trial. Per drug, a median of 17% (IQR 8–20%) of trials supporting FDA approvals were subject to FDAAA mandated public disclosure; of these, a median of 67% (IQR 0–100%) were FDAAA-compliant. 68% of research participants (67 629 of 99 599) participated in FDAAA-subject trials, with 51% (33 405 of 67 629) enrolled in non-compliant trials. Transparency varied widely among companies. Conclusions Trial disclosures for new drugs remain below legal and ethics standards, with wide variation in practices among drugs and their sponsors. Best practices are emerging. 2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve

  1. Mitochondrial iron-sulfur cluster biogenesis from molecular understanding to clinical disease

    Science.gov (United States)

    Alfadhel, Majid; Nashabat, Marwan; Ali, Qais Abu; Hundallah, Khalid

    2017-01-01

    Iron–sulfur clusters (ISCs) are known to play a major role in various protein functions. Located in the mitochondria, cytosol, endoplasmic reticulum and nucleus, they contribute to various core cellular functions. Until recently, only a few human diseases related to mitochondrial ISC biogenesis defects have been described. Such diseases include Friedreich ataxia, combined oxidative phosphorylation deficiency 19, infantile complex II/III deficiency defect, hereditary myopathy with lactic acidosis and mitochondrial muscle myopathy, lipoic acid biosynthesis defects, multiple mitochondrial dysfunctions syndromes and non ketotic hyperglycinemia due to glutaredoxin 5 gene defect. Disorders of mitochondrial import, export and translation, including sideroblastic anemia with ataxia, EVEN-PLUS syndrome and mitochondrial complex I deficiency due to nucleotide-binding protein-like protein gene defect, have also been implicated in ISC biogenesis defects. With advances in next generation sequencing technologies, more disorders related to ISC biogenesis defects are expected to be elucidated. In this article, we aim to shed the light on mitochondrial ISC biogenesis, related proteins and their function, pathophysiology, clinical phenotypes of related disorders, diagnostic approach, and future implications. PMID:28064324

  2. Studies on Ancylostomiasis: II.Clinical Symptomatology, Effects of Drugs, especially of Iron Compounds, with Relation to the Severity of Artificial Infection

    International Nuclear Information System (INIS)

    Lee, Mun Ho; Kim, Dong Jip; Lee, Jang Kyu; Seo, Byong Sul

    1967-01-01

    This study was aimed; firstly to observe various clinical symptomatology with relation to the number of Ancylostoma duodenale larvae orally given to the human beings, secondly to evaluate the effects of some drugs like steroid hormones, antihistaminics and antitussives, and, thirdly to study the influences of some iron compounds in prevention and treatment of anemia of such origin. Ten healthy volunteers free from the previous history of hookworm infection were divided into 4 groups, to whom various numbers of actively moving filariform Ancylostoma duodenale larvae were orally given; 500 to 4 cases, 250 to 3 cases and 100 to 3 cases. Following were the results: 1. Clinical symptomatology. 1) The most frequently encountered symptoms and signs were general malaise, cough and hoarseness. The tracheal itching and pain, low back pain, arthralgia, sputum and salivation, acid belching, loss of appetite, abdominal pain and vomiting were also noted. 2) If the larger number of the larvae was given, the clinical symptomatology was more severe. 3) Prednisolone medication caused some improvement of such symptomatology, while the antihistaminics and antitussives like codeine or ephedrine were ineffective. 4) In volunteers whose nutritional conditions were rather poor appeared to show more severe symptomatology. 2. Effects of iron compounds. 1) The oral administration of ferrous fumarate induced a slight increase of serum iron levels in the initial stage of the infection, then a decrease from 15-20 days later and a recovery after 2 months. 2) The intravenous administration of saccharated ferric oxide induced a steady upkeep of the serum iron levels. 3) The hemoglobin contents also showed the upkeeps after either the oral or intravenous administration of the iron compounds. 4) The iron compounds, therefore, are considered to have the preventive as well as the therapeutic effects on hookworm anemia, which may strongly suggest that hookworm anemia is essentially the iron deficiency

  3. Studies on Ancylostomiasis: II.Clinical Symptomatology, Effects of Drugs, especially of Iron Compounds, with Relation to the Severity of Artificial Infection

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mun Ho; Kim, Dong Jip; Lee, Jang Kyu; Seo, Byong Sul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1967-09-15

    This study was aimed; firstly to observe various clinical symptomatology with relation to the number of Ancylostoma duodenale larvae orally given to the human beings, secondly to evaluate the effects of some drugs like steroid hormones, antihistaminics and antitussives, and, thirdly to study the influences of some iron compounds in prevention and treatment of anemia of such origin. Ten healthy volunteers free from the previous history of hookworm infection were divided into 4 groups, to whom various numbers of actively moving filariform Ancylostoma duodenale larvae were orally given; 500 to 4 cases, 250 to 3 cases and 100 to 3 cases. Following were the results: 1. Clinical symptomatology. 1) The most frequently encountered symptoms and signs were general malaise, cough and hoarseness. The tracheal itching and pain, low back pain, arthralgia, sputum and salivation, acid belching, loss of appetite, abdominal pain and vomiting were also noted. 2) If the larger number of the larvae was given, the clinical symptomatology was more severe. 3) Prednisolone medication caused some improvement of such symptomatology, while the antihistaminics and antitussives like codeine or ephedrine were ineffective. 4) In volunteers whose nutritional conditions were rather poor appeared to show more severe symptomatology. 2. Effects of iron compounds. 1) The oral administration of ferrous fumarate induced a slight increase of serum iron levels in the initial stage of the infection, then a decrease from 15-20 days later and a recovery after 2 months. 2) The intravenous administration of saccharated ferric oxide induced a steady upkeep of the serum iron levels. 3) The hemoglobin contents also showed the upkeeps after either the oral or intravenous administration of the iron compounds. 4) The iron compounds, therefore, are considered to have the preventive as well as the therapeutic effects on hookworm anemia, which may strongly suggest that hookworm anemia is essentially the iron deficiency

  4. Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants.

    Science.gov (United States)

    Ma, Julian K-C; Drossard, Jürgen; Lewis, David; Altmann, Friedrich; Boyle, Julia; Christou, Paul; Cole, Tom; Dale, Philip; van Dolleweerd, Craig J; Isitt, Valerie; Katinger, Dietmar; Lobedan, Martin; Mertens, Hubert; Paul, Mathew J; Rademacher, Thomas; Sack, Markus; Hundleby, Penelope A C; Stiegler, Gabriela; Stoger, Eva; Twyman, Richard M; Vcelar, Brigitta; Fischer, Rainer

    2015-10-01

    Although plant biotechnology has been widely investigated for the production of clinical-grade monoclonal antibodies, no antibody products derived from transgenic plants have yet been approved by pharmaceutical regulators for clinical testing. In the Pharma-Planta project, the HIV-neutralizing human monoclonal antibody 2G12 was expressed in transgenic tobacco (Nicotiana tabacum). The scientific, technical and regulatory demands of good manufacturing practice (GMP) were addressed by comprehensive molecular characterization of the transgene locus, confirmation of genetic and phenotypic stability over several generations of transgenic plants, and by establishing standard operating procedures for the creation of a master seed bank, plant cultivation, harvest, initial processing, downstream processing and purification. The project developed specifications for the plant-derived antibody (P2G12) as an active pharmaceutical ingredient (API) based on (i) the guidelines for the manufacture of monoclonal antibodies in cell culture systems; (ii) the draft European Medicines Agency Points to Consider document on quality requirements for APIs produced in transgenic plants; and (iii) de novo guidelines developed with European national regulators. From the resulting process, a GMP manufacturing authorization was issued by the competent authority in Germany for transgenic plant-derived monoclonal antibodies for use in a phase I clinical evaluation. Following preclinical evaluation and ethical approval, a clinical trial application was accepted by the UK national pharmaceutical regulator. A first-in-human, double-blind, placebo-controlled, randomized, dose-escalation phase I safety study of a single vaginal administration of P2G12 was carried out in healthy female subjects. The successful completion of the clinical trial marks a significant milestone in the commercial development of plant-derived pharmaceutical proteins. © 2015 Society for Experimental Biology, Association of

  5. Iron chelators ICL670 and 311 inhibit HIV-1 transcription

    International Nuclear Information System (INIS)

    Debebe, Zufan; Ammosova, Tatyana; Jerebtsova, Marina; Kurantsin-Mills, Joseph; Niu, Xiaomei; Charles, Sharroya; Richardson, Des R.; Ray, Patricio E.; Gordeuk, Victor R.; Nekhai, Sergei

    2007-01-01

    HIV-1 replication is induced by an excess of iron and iron chelation by desferrioxamine (DFO) inhibits viral replication by reducing proliferation of infected cells. Treatment of cells with DFO and 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) inhibit expression of proteins that regulate cell-cycle progression, including cycle-dependent kinase 2 (CDK2). Our recent studies showed that CDK2 participates in HIV-1 transcription and viral replication suggesting that inhibition of CDK2 by iron chelators might also affect HIV-1 transcription. Here we evaluated the effect of a clinically approved orally effective iron chelator, 4-[3,5-bis-(hydroxyphenyl)-1,2,4-triazol-1-yl]-benzoic acid (ICL670) and 311 on HIV-1 transcription. Both ICL670 and 311 inhibited Tat-induced HIV-1 transcription in CEM-T cells, 293T and HeLa cells. Neither ICL670 nor 311 induced cytotoxicity at concentrations that inhibited HIV-1 transcription. The chelators decreased cellular activity of CDK2 and reduced HIV-1 Tat phosphorylation by CDK2. Neither ICL670A or 311 decreased CDK9 protein level but significantly reduced association of CDK9 with cyclin T1 and reduced phosphorylation of Ser-2 residues of RNA polymerase II C-terminal domain. In conclusion, our findings add to the evidence that iron chelators can inhibit HIV-1 transcription by deregulating CDK2 and CDK9. Further consideration should be given to the development of iron chelators for future anti-retroviral therapeutics

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... our clinical trials . Are you a frequent blood donor living in New York City? This study is looking at how iron-deficiency anemia in blood donors affects the quality of donated red blood cells, ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness ... If your doctor diagnoses you with iron-deficiency anemia, your treatment will depend on the cause and severity of the condition. Your ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... blocks the intestine from taking up iron. Other medical conditions Other medical conditions that may lead to ... to advancing science and translating discoveries into clinical practice to promote the prevention and treatment of heart, ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ... infancy has lasting effects. We are interested in learning how having iron-deficiency anemia early in life ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... clinical trials to improve health, and where to find more information. Causes Your body needs iron to ... common symptom. This can make it hard to find the energy to do normal activities. Headache Irregular ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... in our clinical trials . Are you a frequent blood donor living in New York City? This study is looking at how iron-deficiency anemia in blood donors affects the quality of donated red blood cells, ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... an MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such ... explain our ongoing clinical studies that are investigating prevention strategies for iron-deficiency anemia. Signs, Symptoms, and ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... to learn more about iron-deficiency anemia, our role in research and clinical trials to improve health, ... of Blood Diseases and Resources (DBDR) is a leader in research on the causes, prevention, and treatment ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such as ... our ongoing clinical studies that are investigating prevention strategies for iron-deficiency anemia. Signs, Symptoms, and Complications ...

  15. Does Fat Suppression via Chemically Selective Saturation (CHESS) Affect R2*-MRI for Transfusional Iron Overload Assessment? A Clinical Evaluation at 1.5 and 3 Tesla

    Science.gov (United States)

    Krafft, Axel J.; Loeffler, Ralf B.; Song, Ruitian; Bian, Xiao; McCarville, M. Beth; Hankins, Jane S.; Hillenbrand, Claudia M.

    2015-01-01

    Purpose Fat suppression (FS) via chemically selective saturation (CHESS) eliminates fat-water oscillations in multi-echo gradient echo (mGRE) R2*-MRI. However, for increasing R2* values as seen with increasing liver iron content (LIC), the water signal spectrally overlaps with the CHESS band, which may alter R2*. Here, we investigate the effect of CHESS on R2* and describe a heuristic correction for the observed CHESS-induced R2* changes. Methods Eighty patients (49/31 female/male, mean age: 18.3±11.7 years) with iron overload were scanned with a non-FS and a CHESS-FS mGRE sequence at 1.5T and 3T. Mean liver R2* values were evaluated using 3 published fitting approaches. Measured and model-corrected R2* values were compared and statistically analyzed. Results At 1.5T, CHESS led to a systematic R2* reduction (PCHESS-induced R2* bias after correction (linear regression slopes: 1.032/0.927/0.981). No CHESS-induced R2* reductions were found at 3T. Conclusion The CHESS-induced R2* bias at 1.5T needs to be considered when applying R2*-LIC biopsy calibrations for clinical LIC assessment which were established without FS at 1.5T. The proposed model corrects the R2* bias and could therefore improve clinical iron overload assessment based on linear R2*-LIC calibrations. PMID:26308155

  16. Effect of Combined versus Monotherapy with Deferoxamine and Deferiprone in Iron Overloaded Thalassemia Patients: a Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Sasan Hejazi

    2016-06-01

    Full Text Available Background: Patients with transfusional iron overload have depended on iron chelation therapy and improving chelation regimens have been of the highest priority. The aim of this study was to compare effect of combined versus monotherapy with Deferoxamine (DFO and Deferiprone (DFP in iron overloaded beta thalassemia (BT major patients Materials and Methods We studied 36 BT major patients (mean age 7.6±4.6; range 3–16 years attending the Ormieh Motahari hospital for regular transfusional support. Patients were randomly allocated to receive one of the following two treatments: DFO in combination with DFP (n=12, DFO alone (n=12 and DFP alone (n=12. Serum ferritin level, liver enzymes, blood urea nitrogen, and creatinine and side effects were monitored over a 12 months period. Results: After one year, serum ferritin decreased more significantly in patients on DFO+DFP therapy compared to patients who only received DFO or DFP alone (P

  17. 77 FR 74670 - Draft Guidance for Industry on Enrichment Strategies for Clinical Trials to Support Approval of...

    Science.gov (United States)

    2012-12-17

    ... drug applications (NDAs) and biologics license applications (BLAs). This document defines several types... to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm... applications (BLAs). Similar approaches could be used in clinical trials in earlier phases of drug development...

  18. [Iron deficiency and pica].

    Science.gov (United States)

    Muñoz, J A; Marcos, J; Risueño, C E; de Cos, C; López, R; Capote, F J; Martín, M V; Gil, J L

    1998-02-01

    To study the relationship between pica and iron-lack anaemia in a series of iron-deficiency patients in order to establish the pathogenesis of such relationship. Four-hundred and thirty-three patients were analysed. Pica was studied by introducing certain diet queries into the clinical history. All patients received oral iron and were periodically controlled with the usual clinico-haematological procedures. Pica was present in 23 patients (5.3%). Eight nourishing (namely, coffee grains, almonds, chocolate, ice, lettuce, carrots, sunflower seeds and bread) and 2 non-nourishing (clay and paper) substances were involved. A second episode of pica appeared in 9 cases upon relapsing of iron deficiency. Both anaemia and pica were cured by etiologic and substitutive therapy in all instances. No clear correlation was found with either socio-economic status or pathogenetic causes of iron deficiency and pica, and no haematological differences were seen between patients with pica and those without this alteration. (1) The pathogenesis of pica is unclear, although it appears unrelated to the degree of iron deficiency. (2) According to the findings in this series, pica seems a consequence of iron deficiency rather than its cause. (3) Adequate therapy can cure both conditions, although pica may reappear upon relapse of iron deficiency.

  19. Glioblastoma update: molecular biology, diagnosis, treatment, response assessment, and translational clinical trials [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Frank Lieberman

    2017-10-01

    Full Text Available This is an exciting time in neuro-oncology. Discoveries elucidating the molecular mechanisms of oncogenesis and the molecular subtypes of glioblastoma multiforme (GBM have led to new diagnostic and classification schemes with more prognostic power than histology alone. Molecular profiling has become part of the standard neuropathological evaluation of GBM. Chemoradiation followed by adjuvant temozolomide remains the standard therapy for newly diagnosed GBM, but survival remains unsatisfactory. Patients with recurrent GBM continue to have a dismal prognosis, but neuro-oncology centers with active clinical trial programs are seeing a small but increasing cadre of patients with longer survival. Molecularly targeted therapeutics, personalized therapy based on molecular profiling of individual tumors, and immunotherapeutic strategies are all being evaluated and refined in clinical trials. Understanding of the molecular mechanisms of tumor-mediated immunosuppression, and specifically interactions between tumor cells and immune effector cells in the tumor microenvironment, has led to a new generation of immunotherapies, including vaccine and immunomodulatory strategies as well as T-cell-based treatments. Molecularly targeted therapies, chemoradiation, immunotherapies, and anti-angiogenic therapies have created the need to develop more reliable neuroimaging criteria for differentiating the effects of therapy from tumor progression and changes in blood–brain barrier physiology from treatment response. Translational clinical trials for patients with GBM now incorporate quantitative imaging using both magnetic resonance imaging and positron emission tomography techniques. This update presents a summary of the current standards for therapy for newly diagnosed and recurrent GBM and highlights promising translational research.

  20. Laser induced fragmentation of salivary stones: an in vitro comparison of two different, clinically approved laser systems.

    Science.gov (United States)

    Siedek, Vanessa; Betz, Christian S; Hecht, Volkmar; Blagova, Radka; Vogeser, Michael; Zengel, Pamela; Berghaus, Alexander; Leunig, Andreas; Sroka, Ronald

    2008-04-01

    Clinical laser lithotripsy in urology promises a good fragmentation combined with a minimal risk of soft tissue damage and low medical complications. This in vitro study investigates the fragmentation of salivary stones by means of two clinically used laser systems. The effects induced by the FREDDY laser (WOM, Germany, lambda = 532 nm/1,064 nm, E(pulse) = 120-160 mJ/pulse) and the Ho:YAG (AURIGA, StarMedTec, Germany, lambda = 2,100 nm, E(pulse) = 300-800 mJ/pulse) on clinical salivary calculi (n = 15) and on salivary gland tissue were investigated using clinical laser parameter settings. All experiments were performed in an under water experimental set-up using flexible fibres (core diameter 230 microm) positioned in front of each specimen. In order to assess fragmentation efficacy, each stone was placed on a grating (rhombic mash-diameter 1-3 mm). The fragmentation rate was calculated with respect to the energy applied (mg/J), to the number of pulses (mg/pulse), and to the time needed (mg/minute). In addition the composition of the stones were analysed spectrographically. The soft tissue interaction on human salivary duct mucosa was examined histologically (HE-staining). Spectrographic composition of the salivary stones showed a two component ratio of protein/carbonate apatite varying between 5/95 and 25/75. Stones treated by the Ho:YAG were vaporised in a milling-like process, while using the FREDDY laser stones are cracked into pieces and fragmentation failed in two cases. The fragmentation rates achieved by the FREDDY laser were greater than those of the Ho:YAG laser, but fragments mainly bigger. A dependency on the composition of the stones could not be found. Laser pulse effects on soft tissue were found slightly beyond the mucosa. This study clearly demonstrated the different processes of destroying salivary stones using two different laser systems. While the Ho:YAG vaporises the calculi in a more milling and soft sense, the FREDDY shows a more cracking and

  1. Advances in the understanding and clinical management of mastocytosis and clonal mast cell activation syndromes [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    David González-de-Olano

    2016-11-01

    Full Text Available Clonal mast cell activation syndromes and indolent systemic mastocytosis without skin involvement are two emerging entities that sometimes might be clinically difficult to distinguish, and they involve a great challenge for the physician from both a diagnostic and a therapeutic point of view. Furthermore, final diagnosis of both entities requires a bone marrow study; it is recommended that this be done in reference centers. In this article, we address the current consensus and guidelines for the suspicion, diagnosis, classification, treatment, and management of these two entities.

  2. New insights into iron deficiency and iron deficiency anemia.

    Science.gov (United States)

    Camaschella, Clara

    2017-07-01

    Recent advances in iron metabolism have stimulated new interest in iron deficiency (ID) and its anemia (IDA), common conditions worldwide. Absolute ID/IDA, i.e. the decrease of total body iron, is easily diagnosed based on decreased levels of serum ferritin and transferrin saturation. Relative lack of iron in specific organs/tissues, and IDA in the context of inflammatory disorders, are diagnosed based on arbitrary cut offs of ferritin and transferrin saturation and/or marker combination (as the soluble transferrin receptor/ferritin index) in an appropriate clinical context. Most ID patients are candidate to traditional treatment with oral iron salts, while high hepcidin levels block their absorption in inflammatory disorders. New iron preparations and new treatment modalities are available: high-dose intravenous iron compounds are becoming popular and indications to their use are increasing, although long-term side effects remain to be evaluated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Risk of Clinically Relevant Pharmacokinetic-based Drug-drug Interactions with Drugs Approved by the U.S. Food and Drug Administration Between 2013 and 2016.

    Science.gov (United States)

    Yu, Jingjing; Zhou, Zhu; Tay-Sontheimer, Jessica; Levy, Rene H; Ragueneau-Majlessi, Isabelle

    2018-03-23

    A total of 103 drugs (including 14 combination drugs) were approved by the U.S. Food and Drug Administration from 2013 to 2016. Pharmacokinetic-based drug interaction profiles were analyzed using the University of Washington Drug Interaction Database and the clinical relevance of these observations was characterized based on information from New Drug Application reviews. CYP3A was identified as a major contributor to clinical drug-drug interactions (DDIs), involved in approximately 2/3 of all interactions. Transporters (alone or with enzymes) were found to participate in about half of all interactions, although most of these were weak-to-moderate interactions. When considered as victims, eight new molecular entities (NMEs; cobimetinib, ibrutnib, isavuconazole, ivabradine, naloxegol, paritaprevir, simeprevir, and venetoclax) were identified as sensitive substrates of CYP3A, two NMEs (pirfenidone and tasimelteon) were sensitive substrates of CYP1A2, one NME (dasabuvir) was a sensitive substrate of CYP2C8, one NME (eliglustat) was a sensitive substrate of CYP2D6, and one NME (grazoprevir) was a sensitive substrate of OATP1B1/3 (with changes in exposure greater than 5-fold when co-administered with a strong inhibitor). Interestingly, approximately 75% of identified CYP3A substrates were also substrates of P-gp. As perpetrators, most clinical DDIs involved weak-to-moderate inhibition or induction, with only two drugs (Viekira Pak and idelalisib) showing strong inhibition of CYP3A, and one NME (lumacaftor) considered as a strong CYP3A inducer. Among drugs with large changes in exposure (≥ 5-fold), whether as victim or perpetrator, the most represented therapeutic classes were antivirals and oncology drugs, suggesting a significant risk of clinical DDIs in these patient populations. The American Society for Pharmacology and Experimental Therapeutics.

  4. Identification of selective inhibitors of RET and comparison with current clinical candidates through development and validation of a robust screening cascade [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Amanda J. Watson

    2016-05-01

    Full Text Available RET (REarranged during Transfection is a receptor tyrosine kinase, which plays pivotal roles in regulating cell survival, differentiation, proliferation, migration and chemotaxis. Activation of RET is a mechanism of oncogenesis in medullary thyroid carcinomas where both germline and sporadic activating somatic mutations are prevalent.   At present, there are no known specific RET inhibitors in clinical development, although many potent inhibitors of RET have been opportunistically identified through selectivity profiling of compounds initially designed to target other tyrosine kinases. Vandetanib and cabozantinib, both multi-kinase inhibitors with RET activity, are approved for use in medullary thyroid carcinoma, but additional pharmacological activities, most notably inhibition of vascular endothelial growth factor - VEGFR2 (KDR, lead to dose-limiting toxicity. The recent identification of RET fusions present in ~1% of lung adenocarcinoma patients has renewed interest in the identification and development of more selective RET inhibitors lacking the toxicities associated with the current treatments.   In an earlier publication [Newton et al, 2016; 1] we reported the discovery of a series of 2-substituted phenol quinazolines as potent and selective RET kinase inhibitors. Here we describe the development of the robust screening cascade which allowed the identification and advancement of this chemical series.  Furthermore we have profiled a panel of RET-active clinical compounds both to validate the cascade and to confirm that none display a RET-selective target profile.

  5. Improving efficiency and value in health care. Intravenous iron management for anaemia associated with chronic kidney disease: linking treatment to an outpatient clinic, optimizing service provision and patient choice.

    Science.gov (United States)

    Bhandari, Sunil; Naudeer, Sarah

    2008-12-01

    The National Service Framework advocates correction of anaemia in patients with chronic kidney disease (CKD). Oral iron is insufficient, while intravenous (IV) supplementation replenishes and maintains iron stores. In Yorkshire numerous peripheral clinics exist to reduce travel for patients, but patients must travel to the main unit for IV iron therapy. Therefore an outpatient service in tandem with a routine clinic for administration of IV CosmoFer was created. To evaluate the feasibility and benefits of IV iron therapy in the outpatient clinic during active patient review for CKD patients. A cross-sectional study of patients attending for total dose IV iron (n = 57) at a peripheral clinic. Iron was administered and monitored according to protocol by one of the clinic nurses with medical staff available in the adjoining room. Haemoglobin, ferritin and renal function were recorded pre-infusion and after 4-6 months. Results are given as medians/means +/- standard error. A total of 76 IV infusions were carried out with no reported side effects or haemodynamic instability. Haemoglobin (median 10.9 vs. 11.3 g dL(-1), P = NS), creatinine and estimated glomerular filtration rate (eGFR) over the 6-month period remained stable. Serum ferritin rose significantly [80.9 +/- 6.2 vs. 186.4 +/- 18.2 g L(-1) (P Hospital time saved 380 day case bed hours, doctor hours saved 76 hours, and patient hours saved 3 hours/patient. Cost savings for TDI CosmoFer in peripheral clinic versus in centre therapy and versus sucrose, respectively, for 76 treatments was pound 5749.40 and pound 46,320.80 respectively. We have demonstrated, in a resource-limited service, the feasibility and cost-effectiveness of a management care pathway for patients with CKD, in a peripheral clinic, to receive total dose IV CosmoFer without disruption of a functioning renal clinic.

  6. Rethinking Iron Regulation and Assessment in Iron Deficiency, Anemia of Chronic Disease, and Obesity: Introducing Hepcidin

    Science.gov (United States)

    Tussing-Humphreys, Lisa; Pustacioglu, Cenk; Nemeth, Elizabeta; Braunschweig, Carol

    2012-01-01

    Adequate iron availability is essential to human development and overall health. Iron is a key component of oxygen-carrying proteins, has a pivotal role in cellular metabolism, and is essential to cell growth and differentiation. Inadequate dietary iron intake, chronic and acute inflammatory conditions, and obesity are each associated with alterations in iron homeostasis. Tight regulation of iron is necessary because iron is highly toxic and human beings can only excrete small amounts through sweat, skin and enterocyte sloughing, and fecal and menstrual blood loss. Hepcidin, a small peptide hormone produced mainly by the liver, acts as the key regulator of systemic iron homeostasis. Hepcidin controls movement of iron into plasma by regulating the activity of the sole known iron exporter ferroportin-1. Downregulation of the ferroportin-1 exporter results in sequestration of iron within intestinal enterocytes, hepatocytes, and iron-storing macrophages reducing iron bioavailability. Hepcidin expression is increased by higher body iron levels and inflammation and decreased by anemia and hypoxia. Importantly, existing data illustrate that hepcidin may play a significant role in the development of several iron-related disorders, including the anemia of chronic disease and the iron dysregulation observed in obesity. Therefore, the purpose of this article is to discuss iron regulation, with specific emphasis on systemic regulation by hepcidin, and examine the role of hepcidin within several disease states, including iron deficiency, anemia of chronic disease, and obesity. The relationship between obesity and iron depletion and the clinical assessment of iron status will also be reviewed. PMID:22717199

  7. An instrument assessing satisfaction with iron chelation therapy: Psychometric testing from an open-label clinical trial.

    Science.gov (United States)

    Rofail, Diana; Viala, Muriel; Gater, Adam; Abetz-Webb, Linda; Baladi, Jean-Francois; Cappellini, Maria Domenica

    2010-08-01

    The Satisfaction with Iron Chelation Therapy (SICT) instrument was developed based on a literature review, in-depth patient and clinician interviews, and cognitive debriefing interviews. An, open-label, single arm, multicenter trial evaluating the efficacy and safety of deferasirox in patients diagnosed with transfusion-dependent iron overload, provided an opportunity to assess the psychometric measurement properties of the instrument. Psychometric analyses were performed using data at baseline from 273 patients with a range of transfusion-dependent iron overload conditions who were participating in a multinational study. Responsiveness was further evaluated for all patients who also had subsequent satisfaction domain scores collected at week 4. Baseline SICT domain scores had acceptable floor and ceiling effects and internal consistency reliability (Cronbach's alpha: 0.75-0.85). Item discriminant and item convergent validity were both excellent although one item in each analysis did not meet the specified criterion. Small to moderate correlations were observed between SICT and Short Form 36 Health Survey (SF-36) domain scores. Patients with the highest levels of serum ferritin at baseline (>3100 ng/mL) were the least satisfied about the Perceived Effectiveness of ICT and vice versa. Satisfaction improved in all patients, although there were no clear differences observed between groups of patients defined according to changes in serum ferritin levels from baseline to week 4 (stable, improved, or worsened). The SICT domains are reliable and valid. Further testing using a more specific criterion (such as assessing patient global ratings of change in satisfaction domains that correspond to the SICT domains) could help to establish with greater confidence the responsiveness of the instrument.

  8. Linaclotide: first global approval.

    Science.gov (United States)

    McWilliams, Vanessa; Whiteside, Glenn; McKeage, Kate

    2012-11-12

    Linaclotide is a once-daily, orally administered, first-in-class agonist of guanylate cyclase-C that is minimally absorbed. It is being developed to treat gastrointestinal disorders by Ironwood Pharmaceuticals and its partners, Forest Laboratories (North America), Almirall (Europe) and Astellas Pharma (Asia-Pacific). Linaclotide has received its first global approval in the US for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation (CIC), and a marketing submission has been filed in the EU for IBS-C. This article summarizes the milestones in the development of linaclotide leading to this first approval for IBS-C and CIC. This profile has been extracted and modified from the Adis R&D Insight drug pipeline database. Adis R&D Insight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch.

  9. Intrinsic fluorescence of the clinically approved multikinase inhibitor nintedanib reveals lysosomal sequestration as resistance mechanism in FGFR-driven lung cancer.

    Science.gov (United States)

    Englinger, Bernhard; Kallus, Sebastian; Senkiv, Julia; Heilos, Daniela; Gabler, Lisa; van Schoonhoven, Sushilla; Terenzi, Alessio; Moser, Patrick; Pirker, Christine; Timelthaler, Gerald; Jäger, Walter; Kowol, Christian R; Heffeter, Petra; Grusch, Michael; Berger, Walter

    2017-09-07

    Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFRs) constitute a promising therapy target in several types of malignancies including lung cancer. The clinically approved small-molecule FGFR inhibitor nintedanib exerts strong cytotoxicity in FGFR-driven lung cancer cells. However, subcellular pharmacokinetics of this compound and its impact on therapeutic efficacy remain obscure. 3-dimensional fluorescence spectroscopy was conducted to asses cell-free nintedanib fluorescence properties. MTT assay was used to determine the impact of the lysosome-targeting agents bafilomycin A1 and chloroquine combined with nintedanib on lung cancer cell viability. Flow cytometry and live cell as well as confocal microscopy were performed to analyze uptake kinetics as well as subcellular distribution of nintedanib. Western blot was conducted to investigate protein expression. Cryosections of subcutaneous tumor allografts were generated to detect intratumoral nintedanib in mice after oral drug administration. Here, we report for the first time drug-intrinsic fluorescence properties of nintedanib in living and fixed cancer cells as well as in cryosections derived from allograft tumors of orally treated mice. Using this feature in conjunction with flow cytometry and confocal microscopy allowed to determine cellular drug accumulation levels, impact of the ABCB1 efflux pump and to uncover nintedanib trapping into lysosomes. Lysosomal sequestration - resulting in an organelle-specific and pH-dependent nintedanib fluorescence - was identified as an intrinsic resistance mechanism in FGFR-driven lung cancer cells. Accordingly, combination of nintedanib with agents compromising lysosomal acidification

  10. Ultrastructural characterization of mesenchymal stromal cells labeled with ultrasmall superparamagnetic iron-oxide nanoparticles for clinical tracking studies

    DEFF Research Database (Denmark)

    Hansen, Louise; Hansen, Alastair B; Mathiasen, Anders B

    2014-01-01

    INTRODUCTION: To evaluate survival and engraftment of mesenchymal stromal cells (MSCs) in vivo, it is necessary to track implanted cells non-invasively with a method, which does not influence cellular ultrastructure and functional characteristics. Iron-oxide particles have been applied for cell...... sequence of trans-activator of transcription (TAT) (IODEX-TAT) and evaluate the effect of labeling on ultrastructure, viability, phenotype and proliferative capacity of the cells. MATERIALS AND METHODS: MSCs were labeled with 5 and 10 μg IODEX-TAT/10(5) cells for 2, 6 and 21 hours. IODEX-TAT uptake...... and cellular ultrastructure were determined by electron microscopy. Cell viability was determined by propidium iodide staining and cell proliferation capacity by 5-bromo-2-deoxyuridine (BrdU) incorporation. Maintenance of stem cell surface markers was determined by flow cytometry. Results. IODEX-TAT labeling...

  11. Iron Supplementation and Altitude: Decision Making Using a Regression Tree

    Directory of Open Access Journals (Sweden)

    Laura A. Garvican-Lewis, Andrew D. Govus, Peter Peeling, Chris R. Abbiss, Christopher J. Gore

    2016-03-01

    Full Text Available Altitude exposure increases the body’s need for iron (Gassmann and Muckenthaler, 2015, primarily to support accelerated erythropoiesis, yet clear supplementation guidelines do not exist. Athletes are typically recommended to ingest a daily oral iron supplement to facilitate altitude adaptations, and to help maintain iron balance. However, there is some debate as to whether athletes with otherwise healthy iron stores should be supplemented, due in part to concerns of iron overload. Excess iron in vital organs is associated with an increased risk of a number of conditions including cancer, liver disease and heart failure. Therefore clear guidelines are warranted and athletes should be discouraged from ‘self-prescribing” supplementation without medical advice. In the absence of prospective-controlled studies, decision tree analysis can be used to describe a data set, with the resultant regression tree serving as guide for clinical decision making. Here, we present a regression tree in the context of iron supplementation during altitude exposure, to examine the association between pre-altitude ferritin (Ferritin-Pre and the haemoglobin mass (Hbmass response, based on daily iron supplement dose. De-identified ferritin and Hbmass data from 178 athletes engaged in altitude training were extracted from the Australian Institute of Sport (AIS database. Altitude exposure was predominantly achieved via normobaric Live high: Train low (n = 147 at a simulated altitude of 3000 m for 2 to 4 weeks. The remaining athletes engaged in natural altitude training at venues ranging from 1350 to 2800 m for 3-4 weeks. Thus, the “hypoxic dose” ranged from ~890 km.h to ~1400 km.h. Ethical approval was granted by the AIS Human Ethics Committee, and athletes provided written informed consent. An in depth description and traditional analysis of the complete data set is presented elsewhere (Govus et al., 2015. Iron supplementation was prescribed by a sports physician

  12. Current status of superparamagnetic iron oxide contrast agents for liver magnetic resonance imaging.

    Science.gov (United States)

    Wang, Yi-Xiang J

    2015-12-21

    Five types of superparamagnetic iron oxide (SPIO), i.e. Ferumoxides (Feridex(®) IV, Berlex Laboratories), Ferucarbotran (Resovist(®), Bayer Healthcare), Ferumoxtran-10 (AMI-227 or Code-7227, Combidex(®), AMAG Pharma; Sinerem(®), Guerbet), NC100150 (Clariscan(®), Nycomed,) and (VSOP C184, Ferropharm) have been designed and clinically tested as magnetic resonance contrast agents. However, until now Resovist(®) is current available in only a few countries. The other four agents have been stopped for further development or withdrawn from the market. Another SPIO agent Ferumoxytol (Feraheme(®)) is approved for the treatment of iron deficiency in adult chronic kidney disease patients. Ferumoxytol is comprised of iron oxide particles surrounded by a carbohydrate coat, and it is being explored as a potential imaging approach for evaluating lymph nodes and certain liver tumors.

  13. Prevalence, clinical profile, iron status, and subject-specific traits for excessive erythrocytosis in andean adults living permanently at 3,825 meters above sea level.

    Science.gov (United States)

    De Ferrari, Aldo; Miranda, J Jaime; Gilman, Robert H; Dávila-Román, Victor G; León-Velarde, Fabiola; Rivera-Ch, Maria; Huicho, Luis; Bernabé-Ortiz, Antonio; Wise, Robert A; Checkley, William

    2014-11-01

    Excessive erythrocytosis (EE) is a prevalent condition in populations living at high altitudes (> 2,500 m above sea level). Few large population-based studies have explored the association between EE and multiple subject-specific traits including oxygen saturation, iron status indicators, and pulmonary function. We enrolled a sex-stratified and age-stratified sample of 1,065 high-altitude residents aged ≥ 35 years from Puno, Peru (3,825 m above sea level) and conducted a standardized questionnaire and physical examination that included spirometry, pulse oximetry, and a blood sample for multiple clinical markers. Our primary objectives were to estimate the prevalence of EE, characterize the clinical profile and iron status indicators of subjects with EE, and describe subject-specific traits associated with EE. Overall prevalence of EE was 4.5% (95% CI, 3.3%-6.0%). Oxygen saturation was significantly lower among EE than non-EE group subjects (85.3% vs 90.1%, P .09 for all values). In multivariable logistic regression, we found that age ≥ 65 years (OR = 2.45, 95% CI, 1.16-5.09), male sex (3.86, 1.78-9.08), having metabolic syndrome (2.66, 1.27-5.75) or being overweight (5.20, 1.95-16.77), pulse oximetry overweight (26.7%), followed by male sex (21.5%), pulse oximetry overweight or having metabolic syndrome were associated with an important fraction of cases in our study population.

  14. Clinical and Imaging Presentation of a Patient with Beta-Propeller Protein-Associated Neurodegeneration, a Rare and Sporadic form of Neurodegeneration with Brain Iron Accumulation (NBIA).

    Science.gov (United States)

    Hattingen, Elke; Handke, Nikolaus; Cremer, Kirsten; Hoffjan, Sabine; Kukuk, Guido Matthias

    2017-12-01

    Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of inherited neurologic disorders with iron accumulation in the basal ganglia, which share magnetic resonance (MR) imaging characteristics, histopathologic and clinical features. According to the affected basal nuclei, clinical features include extrapyramidal movement disorders and varying degrees of intellectual disability status. The most common NBIA subtype is caused by pathogenic variants in PANK2. The hallmark of MR imaging in patients with PANK2 mutations is an eye-of-the-tiger sign in the globus pallidus. We report a 33-year-old female with a rare subtype of NBIA, called beta-propeller protein-associated neurodegeneration (BPAN) with a hitherto unknown missense variant in WDR45. She presented with BPAN's particular biphasic course of neurological symptoms and with a dominant iron accumulation in the midbrain that enclosed a spotty T2-hyperintensity.

  15. Cast irons

    CERN Document Server

    1996-01-01

    Cast iron offers the design engineer a low-cost, high-strength material that can be easily melted and poured into a wide variety of useful, and sometimes complex, shapes. This latest handbook from ASM covers the entire spectrum of one of the most widely used and versatile of all engineered materials. The reader will find the basic, but vital, information on metallurgy, solidification characteristics, and properties. Extensive reviews are presented on the low-alloy gray, ductile, compacted graphite, and malleable irons. New and expanded material has been added covering high-alloy white irons used for abrasion resistance and high-alloy graphitic irons for heat and corrosion resistance. Also discussed are melting furnaces and foundry practices such as melting, inoculation, alloying, pouring, gating and rising, and molding. Heat treating practices including stress relieving, annealing, normalizing, hardening and tempering, autempering (of ductile irons), and surface-hardening treatments are covered, too. ASM Spec...

  16. Optimizing iron delivery in the management of anemia: patient considerations and the role of ferric carboxymaltose

    Directory of Open Access Journals (Sweden)

    Toblli JE

    2014-12-01

    Full Text Available Jorge Eduardo Toblli, Margarita Angerosa Nephrology Section, Department of Internal Medicine, Hospital Alemán, School of Medicine, University of Buenos Aires, Argentina Abstract: With the challenge of optimizing iron delivery, new intravenous (iv iron–carbohydrate complexes have been developed in the last few years. A good example of these new compounds is ferric carboxymaltose (FCM, which has recently been approved by the US Food and Drug Administration for the treatment of iron deficiency anemia in adult patients who are intolerant to oral iron or present an unsatisfactory response to oral iron, and in adult patients with non-dialysis-dependent chronic kidney disease (NDD-CKD. FCM is a robust and stable complex similar to ferritin, which minimizes the release of labile iron during administration, allowing higher doses to be administered in a single application and with a favorable cost-effective rate. Cumulative information from randomized, controlled, multicenter trials on a diverse range of indications, including patients with chronic heart failure, postpartum anemia/abnormal uterine bleeding, inflammatory bowel disease, NDD-CKD, and those undergoing hemodialysis, supports the efficacy of FCM for iron replacement in patients with iron deficiency and iron-deficiency anemia. Furthermore, as FCM is a dextran-free iron–carbohydrate complex (which has a very low risk for hypersensitivity reactions with a small proportion of the reported adverse effects in a large number of subjects who received FCM, it may be considered a safe drug. Therefore, FCM appears as an interesting option to apply high doses of iron as a single infusion in a few minutes in order to obtain the quick replacement of iron stores. The present review on FCM summarizes diverse aspects such as pharmacology characteristics and analyzes trials on the efficacy/safety of FCM versus oral iron and different iv iron compounds in multiple clinical scenarios. Additionally, the

  17. Variation in standards of research compensation and child assent practices: a comparison of 69 institutional review board-approved informed permission and assent forms for 3 multicenter pediatric clinical trials.

    Science.gov (United States)

    Kimberly, Michael B; Hoehn, K Sarah; Feudtner, Chris; Nelson, Robert M; Schreiner, Mark

    2006-05-01

    To systematically compare standards for compensation and child participant assent in informed permission, assent, and consent forms (IP-A-CFs) approved by 55 local institutional review boards (IRBs) reviewing 3 standardized multicenter research protocols. Sixty-nine principal investigators participating in any of 3 national, multicenter clinical trials submitted standardized research protocols for their trials to their local IRBs for approval. Copies of the subsequently IRB-approved IP-A-CFs were then forwarded to an academic clinical research organization. This collection of IRB-approved forms allowed for a quasiexperimental retrospective evaluation of the variation in informed permission, assent, and consent standards operationalized by the local IRBs. Standards for compensation and child participant assent varied substantially across 69 IRB-approved IP-A-CFs. Among the 48 IP-A-CFs offering compensation, monetary compensation was offered by 33 as reimbursement for travel, parking, or food expenses, whereas monetary or material compensation was offered by 22 for subject inconvenience and by 13 for subject time. Compensation ranged widely within and across studies (study 1, $180-1425; study 2, $0-500; and study 3, $0-100). Regarding child participant assent, among the 57 IP-A-CFs that included a form of assent documentation, 33 included a line for assent on the informed permission or consent form, whereas 35 included a separate form written in simplified language. Of the IP-A-CFs that stipulated the documentation of assent, 31 specified > or =1 age ranges for obtaining assent. Informed permission or consent forms were addressed either to parents or child participants. In response to identical clinical trial protocols, local IRBs generate IP-A-CFs that vary considerably regarding compensation and child participant assent.

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, ... iron-fortified foods that have iron added. Vegetarian diets can provide enough iron if you choose nonmeat ...

  19. 21 CFR 314.510 - Approval based on a surrogate endpoint or on an effect on a clinical endpoint other than survival...

    Science.gov (United States)

    2010-04-01

    ... Serious or Life-Threatening Illnesses § 314.510 Approval based on a surrogate endpoint or on an effect on... well-controlled. The applicant shall carry out any such studies with due diligence. ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) ... We are interested in learning how having iron-deficiency anemia early in life ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Our ... more information about Donor Iron Deficiency Study - Red Blood Cells ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and save lives. We are committed to advancing science and translating discoveries into clinical practice to promote the prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the current and future NHLBI efforts to improve health through ...

  3. Ferrous bisglycinate 25 mg iron is as effective as ferrous sulfate 50 mg iron in the prophylaxis of iron deficiency and anemia during pregnancy in a randomized trial

    DEFF Research Database (Denmark)

    Milman, Nils; Jønsson, Lisbeth; Dyre, Pernille

    2014-01-01

    OBJECTIVE: To compare the effects of oral ferrous bisglycinate 25 mg iron/day vs. ferrous sulfate 50 mg iron/day in the prevention of iron deficiency (ID) and iron deficiency anemia (IDA) in pregnant women. Design: Randomized, double-blind, intention-to-treat study. Setting: Antenatal care clinic...

  4. Therapeutic iron : Evaluation of methods to assess intravenous iron safety profiles and the development of a novel formulation for oral iron delivery

    NARCIS (Netherlands)

    Span, K.|info:eu-repo/dai/nl/357800842

    2018-01-01

    Iron treatment is necessary to replenish iron deficit due to several clinical conditions such as chronic diseases. However, as an excess of iron can result in redox imbalance resulting in oxidative stress and thus severe damage to tissue and organs, it is of utmost importance to develop iron

  5. IRON DOME

    African Journals Online (AJOL)

    6 Israeli Navy 'First Arm of the Sea: The Successful Interception of the Iron Dome Rocket .... sky to destroy them whilst in flight to minimise civilian casualties. ..... Including The Moon and Celestial Bodies.53 Demeyere further emphasises the.

  6. Iron overdose

    Science.gov (United States)

    ... tracing) X-ray to detect and track iron tablets through the stomach and intestines Treatment may include: ... BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, PA: Elsevier; 2016: ...

  7. Iron deficiency and anemia in heart failure.

    Science.gov (United States)

    Çavuşoğlu, Yüksel; Altay, Hakan; Çetiner, Mustafa; Güvenç, Tolga Sinan; Temizhan, Ahmet; Ural, Dilek; Yeşilbursa, Dilek; Yıldırım, Nesligül; Yılmaz, Mehmet Birhan

    2017-03-01

    Heart failure is an important community health problem. Prevalence and incidence of heart failure have continued to rise over the years. Despite recent advances in heart failure therapy, prognosis is still poor, rehospitalization rate is very high, and quality of life is worse. Co-morbidities in heart failure have negative impact on clinical course of the disease, further impair prognosis, and add difficulties to treatment of clinical picture. Therefore, successful management of co-morbidities is strongly recommended in addition to conventional therapy for heart failure. One of the most common co-morbidities in heart failure is presence of iron deficiency and anemia. Current evidence suggests that iron deficiency and anemia are more prevalent in patients with heart failure and reduced ejection fraction, as well as those with heart failure and preserved ejection fraction. Moreover, iron deficiency and anemia are referred to as independent predictors for poor prognosis in heart failure. There is strong relationship between iron deficiency or anemia and severity of clinical status of heart failure. Over the last two decades, many clinical investigations have been conducted on clinical effectiveness of treatment of iron deficiency or anemia with oral iron, intravenous iron, and erythropoietin therapies. Studies with oral iron and erythropoietin therapies did not provide any clinical benefit and, in fact, these therapies have been shown to be associated with increase in adverse clinical outcomes. However, clinical trials in patients with iron deficiency in the presence or absence of anemia have demonstrated considerable clinical benefits of intravenous iron therapy, and based on these positive outcomes, iron deficiency has become target of therapy in management of heart failure. The present report assesses current approaches to iron deficiency and anemia in heart failure in light of recent evidence.

  8. Biosimilars approval process.

    Science.gov (United States)

    Zuñiga, Leyre; Calvo, Begoña

    2010-04-01

    For similar biological medicinal products, the so-called biosimilars, clinical trials are required rather than just the bioequivalence studies required to support the registration of a generic small molecule drug product. The EU Directive 2001/83/EC, as amended, stated that where a biological medicinal product which is similar to a reference biological product, does not meet the conditions in the definition of generic medicinal products the results of appropriate pre-clinical tests or clinical trials relating to these conditions must be provided. The challenge is to determine the exact nature of the non-clinical and clinical programme required to gain regulatory approval. The applicant is encouraged to provide a detailed description of the strategy used to demonstrate the biosimilar and the reference product have similar profiles in terms of quality, safety and efficacy. The extent to which comparability can be proven will have quite an impact on how many non-clinical and clinical studies the biosimilar applicant will be required to conduct. The dossier submitted by the applicant to the EMEA should cover all aspects of the comparability assessment and must include data on possible unwanted immune reactions to the therapeutic protein. Post-marketing pharmacovigilance plans are also expected to be included in the biosimilar dossier. Copyright 2009 Elsevier Inc. All rights reserved.

  9. Persistent Microvascular Obstruction After Myocardial Infarction Culminates in the Confluence of Ferric Iron Oxide Crystals, Proinflammatory Burden, and Adverse RemodelingCLINICAL PERSPECTIVE

    Energy Technology Data Exchange (ETDEWEB)

    Kali, Avinash; Cokic, Ivan; Tang, Richard; Dohnalkova, Alice; Kovarik, Libor; Yang, Hsin-Jung; Kumar, Andreas; Prato, Frank S.; Wood, John C.; Underhill, David; Marban, Eduardo; Dharmakumar, Rohan

    2016-11-01

    Emerging evidence now supports the notion that persistent microvascular obstruction (PMO) may be more predictive of major adverse cardiovascular events than MI size itself. But, how PMO, a phenomenon limited to the acute/sub-acute period of MI, imparts adverse remodeling throughout the post MI period, particularly after its resolution, is incompletely understood. We hypothesized that PMOs resolve into chronic iron crystals within MI territories and actively impart a proinflammatory burden and adverse remodeling of infarction and LV in the chronic phase of MI. Canine models reperfused (n=20) and non-reperfused (n=20) with and without PMO were studied with serial cardiac MRI to characterize the spatiotemporal relationships between PMO, iron deposition, and infarct and LV remodeling indices between acute (day 7, post MI) and chronic (week 8, post MI). Histopathology and immunohistochemistry were used to validate the iron deposition, microscopically map and quantify the relationship between iron-rich chronic MI regions against pro-inflammatory macrophages, proinflammatory cytokines and matrix metalloproteinase. Atomic resolution transmission electron microscopy (TEM) was used to determine the crystallinity of iron and assess the physical effects of iron on lysosomes within macrophages, and energy-dispersive X-ray spectroscopy (EDS) to identify the chemical composition of the iron composite. Results showed that PMOs lead to iron deposition within chronic MI and that the extent of chronic iron deposition is strongly related to PMO Volume (r>0.6, p<0.001). TEM and EDS analysis showed that iron within chronic MI is found within macrophages as aggregates of nanocrystals of ~2.5 nm diameter in ferric state. Correlative histological studies showed that iron content, proinflammatory burden and collagen degrading enzyme were highly correlated (r >0.7, p<0.001). Iron within chronic MI was significantly associated with infarct resorption (r>0.5, p<0.001) and adverse structural (r

  10. Preclinical pharmacokinetics, biodistribution, radiation dosimetry and acute toxicity studies required for regulatory approval of a Clinical Trial Application for a Phase I/II clinical trial of 111In-BzDTPA-pertuzumab

    International Nuclear Information System (INIS)

    Lam, Karen; Chan, Conrad; Done, Susan J.; Levine, Mark N.; Reilly, Raymond M.

    2015-01-01

    Introduction: 111 In-BzDTPA-pertuzumab is a novel imaging probe for detecting changes in HER2 expression in breast cancer (BC) caused by treatment with trastuzumab (Herceptin). Our aim was to evaluate the pharmacokinetics, normal tissue biodistribution, radiation dosimetry and acute toxicity of 111 In-BzDTPA-pertuzumab in non-tumor bearing mice in order to obtain regulatory approval to advance this agent to a first-in-humans Phase I/II clinical trial. Methods: Biodistribution and pharmacokinetic studies were performed in non-tumor bearing Balb/c mice injected i.v. with 111 In-BzDTPA-pertuzumab (2.5 MBq; 2 μg). The cumulative number of disintegrations per source organ derived from the biodistribution data was used to predict the radiation absorbed doses in humans using OLINDA/EXM software. Acute toxicity was studied at two weeks post-injection of 111 In-BzDTPA-pertuzumab (1.0 MBq, 20 μg) with comparison to control mice injected with unlabeled BzDTPA-pertuzumab (20 μg) or Sodium Chloride Injection USP. The dose of 111 In-BzDTPA-pertuzumab corresponded to 23-times the human radioactivity dose and 10-times the protein dose on a MBq/kg and mg/kg basis, respectively. Toxicity was assessed by monitoring body mass, complete blood cell count (CBC), hematocrit (Hct), hemoglobin (Hb), serum creatinine (SCr) and alanine aminotransferease (ALT) and by histopathological examination of tissues at necropsy. Results: 111 In-BzDTPA-pertuzumab exhibited a biphasic elimination from the blood with a distribution half-life (t 1/2 α) of 3.8 h and an elimination half-life (t 1/2 β) of 228.2 h. The radiopharmaceutical was distributed mainly in the blood, heart, lungs, liver, kidneys and spleen. The projected whole-body radiation absorbed dose in humans was 0.05 mSv/MBq corresponding to a total of 16.8 mSv for three separate administrations of 111 In-BzDTPA-pertuzumab (111 MBq) planned for the Phase I/II trial. There were slight changes in Hb and SCr levels associated with

  11. Superparamagnetic iron oxides for MRI

    International Nuclear Information System (INIS)

    Weissleder, R.; Reimer, P.

    1993-01-01

    Pharmaceutical iron oxide preparations have been used as MRI contrast agents for a variety of purposes. These agents predominantly decrease T2 relaxation times and therefore cause a decrease in signal intensity of tissues that contain the agent. After intravenous administration, dextran-coated iron oxides typically accumulate in phagocytic cells in liver and spleen. Clinical trials have shown that iron oxide increases lesion/liver and lesion/spleen contrast, that more lesions can be depicted than on plain MRI or CT, and that the size threshold for lesion detection decreases. Decreased uptake of iron oxides in liver has been observed in hepatitis and cirrhosis, potentially allowing the assessment of organ function. More recently a variety of novel, target-specific monocrystalline iron oxides compounds have been used for receptor and immunospecific images. Future development of targeted MRI contrast agents is critical for organ- or tissue-specific quantitative and functional MRI. (orig.)

  12. Superparamagnetic iron oxides for MRI

    Energy Technology Data Exchange (ETDEWEB)

    Weissleder, R [MGH-NMR Center, Dept. of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Reimer, P [MGH-NMR Center, Dept. of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); [Inst. fuer Klinische Radiologie, Zentrale Roentgendiagnostik, Westfaelische-Wilhelms-Univ., Muenster (Germany)

    1993-06-01

    Pharmaceutical iron oxide preparations have been used as MRI contrast agents for a variety of purposes. These agents predominantly decrease T2 relaxation times and therefore cause a decrease in signal intensity of tissues that contain the agent. After intravenous administration, dextran-coated iron oxides typically accumulate in phagocytic cells in liver and spleen. Clinical trials have shown that iron oxide increases lesion/liver and lesion/spleen contrast, that more lesions can be depicted than on plain MRI or CT, and that the size threshold for lesion detection decreases. Decreased uptake of iron oxides in liver has been observed in hepatitis and cirrhosis, potentially allowing the assessment of organ function. More recently a variety of novel, target-specific monocrystalline iron oxides compounds have been used for receptor and immunospecific images. Future development of targeted MRI contrast agents is critical for organ- or tissue-specific quantitative and functional MRI. (orig.)

  13. Disposition, accumulation and toxicity of iron fed as iron (II) sulfate or as sodium iron EDTA in rats

    NARCIS (Netherlands)

    Appel, M.J.; Kuper, C.F.; Woutersen, R.A.

    2001-01-01

    A study was performed to provide data on the disposition, accumulation and toxicity of sodium iron EDTA in comparison with iron (II) sulfate in rats on administration via the diet for 31 and 61 days. Clinical signs, body weights, food consumption, food conversion efficiency, hematology, clinical

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-rich foods, especially during certain stages of life when more iron is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and iron- ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... that are good sources of iron include dried beans, dried fruits, eggs, lean red meat, salmon, iron- ... of iron, including iron-fortified breads and cereals, beans, tofu, dried fruits, and spinach and other dark ...

  16. Iron in diet

    Science.gov (United States)

    ... Reasonable amounts of iron are also found in lamb, pork, and shellfish. Iron from vegetables, fruits, grains, ... strawberries, tomatoes, and potatoes) also increase iron absorption. Cooking foods in a cast-iron skillet can also ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... from developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, ... iron is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron- ... iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... for your body to absorb iron from the gastrointestinal tract (GI tract). Blood loss When you lose blood, ... iron deficiency. Endurance athletes lose iron through their gastrointestinal tracts. They also lose iron through the breakdown of ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron in your body is low. For this reason, other iron tests are also done. Ferritin measure ... iron is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... develop new therapies for conditions that affect the balance of iron in the body and lead to ... Disease Control and Prevention) Iron - Health Professional Fact Sheet (NIH) Iron Dietary Supplement Fact Sheet (NIH) Iron- ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... to moderate iron-deficiency anemia, or red blood cell transfusion for severe iron-deficiency anemia. You may ... body needs iron to make healthy red blood cells. Iron-deficiency anemia usually develops over time because ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... enough iron-rich foods, such as meat and fish, may result in you getting less than the ... pregnancy. Good sources of iron are meat, poultry, fish, and iron-fortified foods that have iron added. ...

  4. Iron Dextran Injection

    Science.gov (United States)

    Iron dextran injection is used to treat iron-deficiency anemia (a lower than normal number of red blood cells ... treated with iron supplements taken by mouth. Iron dextran injection is in a class of medications called ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and severity. Treatments may include iron supplements, procedures, surgery, and dietary ... iron supplements, also called iron pills or oral iron, by mouth once or several times a ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, ... is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and iron- ...

  7. Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation

    Directory of Open Access Journals (Sweden)

    Umashankar A

    2016-04-01

    morphological characteristics of neurons and glia produced after NSC differentiation. Importantly, the transplantation of NSCs labeled with either of the two MIRB doses upregulated the immune response in recipient animals. In particular, in animals receiving the 50 µg/mL MIRB-labeled NSCs, this immune response consisted of an increased number of CD68+-activated microglia, which appeared to have phagocytosed MIRB particles and cells contributing to an exaggerated MRI signal dropout in the animals. Overall, these results indicate that although USPIO particles, such as MIRB, may have advantageous labeling and magnetic resonance-sensitive features for NSC tracking, a further examination of their effects might be necessary before they can be used in clinical scenarios of cell-based transplantation. Keywords: MRI, neural stem cells, iron oxide nanoparticles, USPIO

  8. Iron deficiency anemia in patients with inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Goldberg ND

    2013-06-01

    Full Text Available Neil D Goldberg Emeritus Chief of Gastroenterology, University of Maryland St. Joseph Medical Center, Towson, MD, USA Abstract: Iron deficiency anemia is the most common form of anemia worldwide, caused by poor iron intake, chronic blood loss, or impaired absorption. Patients with inflammatory bowel disease (IBD are increasingly likely to have iron deficiency anemia, with an estimated prevalence of 36%–76%. Detection of iron deficiency is problematic as outward signs and symptoms are not always present. Iron deficiency can have a significant impact on a patient's quality of life, necessitating prompt management and treatment. Effective treatment includes identifying and treating the underlying cause and initiating iron replacement therapy with either oral or intravenous iron. Numerous formulations for oral iron are available, with ferrous fumarate, sulfate, and gluconate being the most commonly prescribed. Available intravenous formulations include iron dextran, iron sucrose, ferric gluconate, and ferumoxytol. Low-molecular weight iron dextran and iron sucrose have been shown to be safe, efficacious, and effective in a host of gastrointestinal disorders. Ferumoxytol is the newest US Food and Drug Administration-approved intravenous iron therapy, indicated for iron deficiency anemia in adults with chronic kidney disease. Ferumoxytol is also being investigated in Phase 3 studies for the treatment of iron deficiency anemia in patients without chronic kidney disease, including subgroups with IBD. A review of the efficacy and safety of iron replacement in IBD, therapeutic considerations, and recommendations for the practicing gastroenterologist are presented. Keywords: anemia, inflammatory bowel disease, intravenous iron, iron deficiency, oral iron, therapy

  9. Effect of Consuming Zinc-fortified Bread on Serum Zinc and Iron Status of Zinc-deficient Women: A Double Blind, Randomized Clinical Trial.

    Science.gov (United States)

    Badii, Akbar; Nekouei, Niloufar; Fazilati, Mohammad; Shahedi, Mohammad; Badiei, Sajad

    2012-03-01

    After iron deficiency, zinc deficiency is the major micronutrient deficiency in developing countries, and staple food fortification is an effective strategy to prevent and improve it among at-risk-populations. No action has been taken to reduce zinc deficiency via flour fortification so far in Iran, and little is known about the influence of zinc fortification of flour on serum zinc and the iron status, and also about the optimum and effective amount of zinc compound that is used in food fortification. The objective of this study is to evaluate the influence of consuming zinc-fortified breads on the zinc and iron status in the blood serum. In this study, three types of bread were prepared from non-fortified and fortified flours, with 50 and 100 ppm elemental zinc in the form of sulfate. Eighty zinc-deficient women aged 19 to 49 years were randomly assigned to three groups; The volunteers received, daily, (1) a non-fortified bread, (2) a high-zinc bread, and (3) a low-zinc bread for one month. Serum zinc and iron were measured by Atomic Absorption before and after the study. Results showed a significant increase in serum zinc and iron levels in all groups (p 0.05). Absorption of zinc and iron in the group that consumed high-zinc bread was significantly greater than that in the group that received low-zinc bread (p bread improved iron absorption.

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  11. Lack of proportionality. Seven specifications of public interest that override post-approval commercial interests on limited access to clinical data

    Directory of Open Access Journals (Sweden)

    Strech Daniel

    2012-07-01

    Full Text Available Abstract For the protection of commercial interests, licensing bodies such as the EMA and health technology assessment institutions such as NICE restrict full access to unpublished evidence. Their respective policies on data transparency, however, lack a systematic account of (1 what kinds of commercial interests remain relevant after market approval has been granted, (2 what the specific types of public interest are that may override these commercial interests post approval, and, most importantly, (3 what criteria guide the trade-off between public interest and legitimate measures for the protection of commercial interest. Comparing potential commercial interests with seven specifications of relevant public interest reveals the lack of proportionality inherent in the current practices of EMA and NICE.

  12. Macroscopic and microscopic biodistribution of intravenously administered iron oxide nanoparticles

    Science.gov (United States)

    Misra, Adwiteeya; Petryk, Alicia A.; Strawbridge, Rendall R.; Hoopes, P. Jack

    2015-03-01

    Iron oxide nanoparticles (IONP) are being developed for use as a cancer treatment. They have demonstrated efficacy when used either as a monotherapy or in conjunction with conventional chemotherapy and radiation. The success of IONP as a therapeutic tool depends on the delivery of a safe and controlled cytotoxic thermal dose to tumor tissue following activation with an alternating magnetic field (AMF). Prior to clinical approval, knowledge of IONP toxicity, biodistribution and physiological clearance is essential. This preliminary time-course study determines the acute toxicity and biodistribution of 110 nm dextran-coated IONP (iron) in mice, 7 days post systemic, at doses of 0.4, 0.6, and 1.0 mg Fe/ g mouse bodyweight. Acute toxicity, manifested as changes in the behavior of mice, was only observed temporarily at 1.0 mg Fe/ g mouse bodyweight, the highest dose administered. Regardless of dose, mass spectrometry and histological analysis demonstrated over 3 mg Fe/g tissue in organs within the reticuloendotheilial system (i.e. liver, spleen, and lymph nodes). Other organs (brain, heart, lungs, and kidney) had less than 0.5 mg Fe/g tissue with iron predominantly confined to the organ vasculature.

  13. Iron and iron derived radicals

    International Nuclear Information System (INIS)

    Borg, D.C.; Schaich, K.M.

    1987-04-01

    We have discussed some reactions of iron and iron-derived oxygen radicals that may be important in the production or treatment of tissue injury. Our conclusions challenge, to some extent, the usual lines of thought in this field of research. Insofar as they are born out by subsequent developments, the lessons they teach are two: Think fast! Think small! In other words, think of the many fast reactions that can rapidly alter the production and fate of highly reactive intermediates, and when considering the impact of competitive reactions on such species, think how they affect the microenvironment (on the molecular scale) ''seen'' by each reactive molecule. 21 refs., 3 figs., 1 tab

  14. Iron Deficiency in Long-Term Parenteral Nutrition Therapy.

    Science.gov (United States)

    Hwa, Yi L; Rashtak, Shahrooz; Kelly, Darlene G; Murray, Joseph A

    2016-08-01

    Iron is not routinely added to parenteral nutrition (PN) formulations in the United States because of the risk of anaphylaxis and concerns about incompatibilities. Studies have shown that iron dextran in non-lipid-containing PN solutions is safe. Data are limited on iron status, prevalence of iron deficiency anemia (IDA), and efficacy of intravenous iron infusion in long-term home PN (HPN). We aimed to determine the incidence of IDA and to examine the effectiveness of parenteral iron replacement in patients receiving HPN. Medical records of patients receiving HPN at the Mayo Clinic from 1977 to 2010 were reviewed. Diagnoses, time to IDA development, and hemoglobin, ferritin, and mean corpuscular volume (MCV) values were extracted. Response of iron indices to intravenous iron replacement was investigated. Of 185 patients (122 women), 60 (32.4%) were iron deficient. Five patients were iron deficient, and 18 had unknown iron status before HPN. Of 93 patients who had sufficient iron storage, 37 had IDA development after a mean of 27.2 months (range, 2-149 months) of therapy. Iron was replaced by adding maintenance iron dextran to PN or by therapeutic iron infusion. Patients with both replacement methods had significant improvement in iron status. With intravenous iron replacement, mean ferritin increased from 10.9 to 107.6 mcg/L (P Parenteral and Enteral Nutrition.

  15. Iron status and cardiovascular disease risk in black South African ...

    African Journals Online (AJOL)

    2011-03-29

    Mar 29, 2011 ... Keywords: iron status, cardiovascular disease, African women, PURE study. Iron status and .... sponsored Arlie Conference.20 Body circumferences of participants ...... cardiovascular disease prevention in clinical practice.

  16. Iron and stony-iron meteorites

    DEFF Research Database (Denmark)

    Ruzicka, Alex M.; Haack, Henning; Chabot, Nancy L.

    2017-01-01

    By far most of the melted and differentiated planetesimals that have been sampled as meteorites are metal-rich iron meteorites or stony iron meteorites. The parent asteroids of these meteorites accreted early and differentiated shortly after the solar system formed, producing some of the oldest...... and interpretations for iron and stony iron meteorites (Plate 13.1). Such meteorites provide important constraints on the nature of metal-silicate separation and mixing in planetesimals undergoing partial to complete differentiation. They include iron meteorites that formed by the solidification of cores...... (fractionally crystallized irons), irons in which partly molten metal and silicates of diverse types were mixed together (silicate-bearing irons), stony irons in which partly molten metal and olivine from cores and mantles were mixed together (pallasites), and stony irons in which partly molten metal...

  17. Trial endpoints for drug approval in oncology: Chemoprevention.

    Science.gov (United States)

    Beitz, J

    2001-04-01

    As with other drugs, new drug applications for marketing approval of chemopreventive drugs must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. This article summarizes the regulatory requirements for traditional marketing approval, as well as for approval under the accelerated approval regulations. Unlike traditional approval, accelerated approval is based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Discussions with the Food and Drug Administration (FDA) regarding the validity of trial endpoints that may serve as surrogates for clinical benefit for accelerated approval should take place as early as possible in drug development. Meetings with the FDA to discuss these issues may be requested throughout the clinical development of a new drug.

  18. Iron Homeostasis in Mycobacterium tuberculosis: Mechanistic Insights into Siderophore-Mediated Iron Uptake

    Science.gov (United States)

    2016-01-01

    Mycobacterium tuberculosis requires iron for normal growth but faces a limitation of the metal ion due to its low solubility at biological pH and the withholding of iron by the mammalian host. The pathogen expresses the Fe3+-specific siderophores mycobactin and carboxymycobactin to chelate the metal ion from insoluble iron and the host proteins transferrin, lactoferrin, and ferritin. Siderophore-mediated iron uptake is essential for the survival of M. tuberculosis, as knockout mutants, which were defective in siderophore synthesis or uptake, failed to survive in low-iron medium and inside macrophages. But as excess iron is toxic due to its catalytic role in the generation of free radicals, regulation of iron uptake is necessary to maintain optimal levels of intracellular iron. The focus of this review is to present a comprehensive overview of iron homeostasis in M. tuberculosis that is discussed in the context of mycobactin biosynthesis, transport of iron across the mycobacterial cell envelope, and storage of excess iron. The clinical significance of the serum iron status and the expression of the iron-regulated protein HupB in tuberculosis (TB) patients is presented here, highlighting the potential of HupB as a marker, notably in extrapulmonary TB cases. PMID:27402628

  19. Effect of consuming zinc-fortified bread on serum zinc and iron status of zinc-deficient women: A double blind, randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Akbar Badii

    2012-01-01

    Full Text Available After iron deficiency, zinc deficiency is the major micronutrient deficiency in developing countries, and staple food fortification is an effective strategy to prevent and improve it among at-risk-populations. No action has been taken to reduce zinc deficiency via flour fortification so far in Iran, and little is known about the influence of zinc fortification of flour on serum zinc and the iron status, and also about the optimum and effective amount of zinc compound that is used in food fortification. The objective of this study is to evaluate the influence of consuming zinc-fortified breads on the zinc and iron status in the blood serum. In this study, three types of bread were prepared from non-fortified and fortified flours, with 50 and 100 ppm elemental zinc in the form of sulfate. Eighty zinc-deficient women aged 19 to 49 years were randomly assigned to three groups; The volunteers received, daily, (1 a non-fortified bread, (2 a high-zinc bread, and (3 a low-zinc bread for one month. Serum zinc and iron were measured by Atomic Absorption before and after the study. Results showed a significant increase in serum zinc and iron levels in all groups (p 0.05. Absorption of zinc and iron in the group that consumed high-zinc bread was significantly greater than that in the group that received low-zinc bread (p < 0.01. It was concluded that fortification of flour with 50-100 ppm zinc was an effective way to achieve adequate zinc intake and absorption in zinc-deficient people. It also appeared that consuming zinc-fortified bread improved iron absorption.

  20. Redfield Energy Approval

    Science.gov (United States)

    This September 19, 2016 letter from EPA approves the petition from Poet Biorefining-Lake Crystal, regarding non-This October 27, 2016 letter from EPA approves the petition from Redfield Energy, LLC, regarding non-grandfathered ethanol produced

  1. Diagnosis of Iron-Deficiency Anemia in Chronic Kidney Disease.

    Science.gov (United States)

    Bahrainwala, Jehan; Berns, Jeffrey S

    2016-03-01

    Anemia is a common and clinically important consequence of chronic kidney disease (CKD). It is most commonly a result of decreased erythropoietin production by the kidneys and/or iron deficiency. Deciding on the appropriate treatment for anemia associated with CKD with iron replacement and erythropoietic-stimulating agents requires an ability to accurately diagnose iron-deficiency anemia. However, the diagnosis of iron-deficiency anemia in CKD patients is complicated by the relatively poor predictive ability of easily obtained routine serum iron indices (eg, ferritin and transferrin saturation) and more invasive gold standard measures of iron deficiency (eg, bone marrow iron stores) or erythropoietic response to supplemental iron. In this review, we discuss the diagnostic utility of currently used serum iron indices and emerging alternative markers of iron stores. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency anemia is a ... address the cause of your iron deficiency, such as any underlying bleeding. If undiagnosed or untreated, iron- ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  4. Iron-Deficiency Anemia

    Science.gov (United States)

    ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  5. Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation.

    Science.gov (United States)

    Umashankar, Abhishek; Corenblum, Mandi J; Ray, Sneha; Valdez, Michel; Yoshimaru, Eriko S; Trouard, Theodore P; Madhavan, Lalitha

    2016-01-01

    An essential component of developing successful neural stem cell (NSC)-based therapies involves the establishment of methodologies to noninvasively monitor grafted NSCs within brain tissues in real time. In this context, ex vivo labeling with ultrasmall superparamagnetic iron oxide (USPIO) particles has been shown to enable efficient tracking of transplanted NSCs via magnetic resonance imaging (MRI). However, whether and how USPIO labeling affects the intrinsic biology of NSCs is not thoroughly understood, and remains an active area of investigation. Here, we perform a comprehensive examination of rat NSC survival and regenerative function upon labeling with the USPIO, Molday ION Rhodamine B (MIRB), which allows for dual magnetic resonance and optical imaging. After optimization of labeling efficiency, two specific doses of MIRB (20 and 50 μg/mL) were chosen and were followed for the rest of the study. We observed that both MIRB doses supported the robust detection of NSCs, over an extended period of time in vitro and in vivo after transplantation into the striata of host rats, using MRI and post hoc fluorescence imaging. Both in culture and after neural transplantation, the higher 50 μg/mL MIRB dose significantly reduced the survival, proliferation, and differentiation rate of the NSCs. Interestingly, although the lower 20 μg/mL MIRB labeling did not produce overtly negative effects, it increased the proliferation and glial differentiation of the NSCs. Additionally, application of this dose also changed the morphological characteristics of neurons and glia produced after NSC differentiation. Importantly, the transplantation of NSCs labeled with either of the two MIRB doses upregulated the immune response in recipient animals. In particular, in animals receiving the 50 μg/mL MIRB-labeled NSCs, this immune response consisted of an increased number of CD68(+)-activated microglia, which appeared to have phagocytosed MIRB particles and cells contributing to an

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... making new blood cells. Visit our Aplastic Anemia Health Topic to learn more. ... recommend that you take iron supplements, also called iron pills or oral iron, by mouth once or several times a ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... red meat, salmon, iron-fortified breads and cereals, peas, tofu, dried fruits, and dark green leafy vegetables. ... stored iron has been used. Ferritin is a protein that helps store iron in your body. Reticulocyte ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... drinking black tea, which reduces iron absorption. Other treatments If you have chronic kidney disease and iron- ... and lifestyle changes to avoid complications. Follow your treatment plan Do not stop taking your prescribed iron ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... diagnoses you with iron-deficiency anemia, your treatment will depend on the cause and severity of the ... of iron. The recommended daily amounts of iron will depend on your age, sex, and whether you ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... heart failure . Increased risk of infections Motor or cognitive development delays in children Pregnancy complications, such as ... iron-deficiency anemia may require intravenous (IV) iron therapy or a blood transfusion . Iron supplements Your doctor ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... because your body’s intake of iron is too low. Low intake of iron can happen because of blood ... delivery or giving birth to a baby with low birth weight In people with chronic conditions, iron- ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... breastfeeding. Recommended daily iron intake for children and adults. The table lists the recommended amounts of iron, ... increased need for iron during growth spurts. Older adults, especially those over age 65. Unhealthy environments Children ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... girls. From birth to 6 months, babies need 0.27 mg of iron. This number goes up ... screen blood donors for low iron stores. Reliable point-of-care testing may help identify iron deficiency ...

  15. Iron metabolism and toxicity

    International Nuclear Information System (INIS)

    Papanikolaou, G.; Pantopoulos, K.

    2005-01-01

    Iron is an essential nutrient with limited bioavailability. When present in excess, iron poses a threat to cells and tissues, and therefore iron homeostasis has to be tightly controlled. Iron's toxicity is largely based on its ability to catalyze the generation of radicals, which attack and damage cellular macromolecules and promote cell death and tissue injury. This is lucidly illustrated in diseases of iron overload, such as hereditary hemochromatosis or transfusional siderosis, where excessive iron accumulation results in tissue damage and organ failure. Pathological iron accumulation in the liver has also been linked to the development of hepatocellular cancer. Here we provide a background on the biology and toxicity of iron and the basic concepts of iron homeostasis at the cellular and systemic level. In addition, we provide an overview of the various disorders of iron overload, which are directly linked to iron's toxicity. Finally, we discuss the potential role of iron in malignant transformation and cancer

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... amount of iron, and medical conditions that make it hard for your body to absorb iron from ... hepcidin. Hepcidin prevents iron from leaving cells where it is stored or from being absorbed in the ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... bleeding. If undiagnosed or untreated, iron-deficiency anemia can cause serious complications, including heart failure and development ... iron is too low. Low intake of iron can happen because of blood loss, consuming less than ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-fortified foods that have iron added. Vegetarian diets can provide enough iron if you choose nonmeat ... Anemia in Chronic Kidney Disease (National Institute of Diabetes and Digestive and Kidney Diseases) Avoiding Anemia (National ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... lean red meat, salmon, iron-fortified breads and cereals, peas, tofu, dried fruits, and dark green leafy ... sources of iron, including iron-fortified breads and cereals, beans, tofu, dried fruits, and spinach and other ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... starch. Restless legs syndrome Shortness of breath Weakness Complications Undiagnosed or untreated iron-deficiency anemia may cause ... as complete blood count and iron studies. Prevent complications over your lifetime To prevent complications from iron- ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... you do not have enough iron in your body. People with mild or moderate iron-deficiency anemia ... and where to find more information. Causes Your body needs iron to make healthy red blood cells. ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... from developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, lean red meat, ... signs of iron-deficiency anemia include: Brittle nails ...

  3. Taking iron supplements

    Science.gov (United States)

    ... medlineplus.gov/ency/article/007478.htm Taking iron supplements To use the sharing features on this page, ... levels. You may also need to take iron supplements as well to rebuild iron stores in your ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... fruits, eggs, lean red meat, salmon, iron-fortified breads and cereals, peas, tofu, dried fruits, and dark ... choose nonmeat sources of iron, including iron-fortified breads and cereals, beans, tofu, dried fruits, and spinach ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... ESAs are usually used with iron therapy or IV iron, or when iron therapy alone is not enough. Look for Living With will discuss what your doctor may recommend, including lifelong lifestyle changes ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and pregnancy. Good sources of iron are meat, poultry, fish, and iron-fortified foods that have iron ... Anemia Restless Legs Syndrome Von Willebrand Disease Other Resources NHLBI resources Your Guide to Anemia [PDF, 1. ...

  7. Ferrotherapy of iron deficiency anemia in children

    OpenAIRE

    Berezhniy V.V.; Korneva V.V.

    2016-01-01

    Present article devoted to the steps for implementation unified clinical protocol of the primary, secondary (specialized) medical care «Iron deficiency» to the practical activities of pediatricians, family physicians. The features of ferrotherapy in children of different age groups and the issues of prevention of iron deficiency states are highlighted.

  8. Eight-year follow-up data from the U.S. clinical trial for Sientra's FDA-approved round and shaped implants with high-strength cohesive silicone gel.

    Science.gov (United States)

    Stevens, W Grant; Harrington, Jennifer; Alizadeh, Kaveh; Broadway, David; Zeidler, Kamakshi; Godinez, Tess B

    2015-05-01

    On March 9, 2012, the Food and Drug Administration (FDA) approved Sientra's premarket approval application for its portfolio of silicone gel breast implants based on their review of Sientra's 3-year study data from the largest pivotal silicone gel breast implant study to date. This included the first approval of shaped breast implants in the United States. The authors provide an update to the 8-year safety and effectiveness of the Sientra High-Strength silicone gel breast implants. The Sientra Core study is an ongoing 10 year open-label, prospective, multi-center clinical study, which includes 1788 patients implanted with 3506 Sientra implants across four indications (Primary Augmentation, Revision Augmentation, Primary Reconstruction, and Revision Reconstruction). For the safety analysis, the incidence of post-operative complications, including all breast implant-related adverse effects (eg, infection, asymmetry), was estimated based on Kaplan-Meier risk rates. The effectiveness analyses include surgeon and patient satisfaction and changes in bra/cup size. Through 8 years, the overall risk of rupture was 4.6%, the risk of capsular contracture was 11.8% (rates were lower when using True Texture™), and the risk of reoperation was 28.3%. Out of the 580 reoperations in 456 patients, over half of all reoperations were due to cosmetic reasons (n = 299). The most common reasons for reoperation were capsular contracture (19.0%), style and/or size change (18.4%), and asymmetry (8.8%). Patient satisfaction remains high through 8 years, with 87% indicating that their breast implants make them feel more feminine than prior to enrollment. Safety data from the FDA Core study continues to support a comprehensive safety and effectiveness profile of Sientra's portfolio of round and shaped implants through 8 years. 3 Therapeutic. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  9. Five-year follow-up data from the U.S. clinical trial for Sientra's U.S. Food and Drug Administration-approved Silimed® brand round and shaped implants with high-strength silicone gel.

    Science.gov (United States)

    Stevens, W Grant; Harrington, Jennifer; Alizadeh, Kaveh; Berger, Lewis; Broadway, David; Hester, T Roderick; Kress, Donald; dʼIncelli, Rosalyn; Kuhne, JoAnn; Beckstrand, Maggi

    2012-11-01

    In March of 2012, the U.S. Food and Drug Administration approved Sientra's application for premarket approval for its Silimed brand silicone gel implants, based on data from the largest silicone gel breast implant study to date. This was the first approval for shaped silicone gel breast implants. This article presents the results of Sientra's study through 5 years. Sientra's study is an ongoing, 10-year, open-label, prospective, multicenter clinical study designed to assess the safety and effectiveness of Sientra's implants in patients undergoing augmentation and reconstruction. A total of 1788 subjects were implanted with 3506 implants, including 1116 primary augmentation, 363 revision-augmentation, 225 primary reconstruction, and 84 revision-reconstruction subjects. Physical evaluations and complications were recorded at each visit. Effectiveness was measured by postimplantation bra cup size and assessment of subject satisfaction and quality of life. Of the 1788 subjects, 571 underwent magnetic resonance imaging to assess silent rupture. Safety endpoints were analyzed using the Kaplan-Meier method. Across all cohorts, the risk of rupture was 1.8 percent (95 percent CI, 1.2 to 2.6 percent), the risk of capsular contracture (Baker grade III/IV) was 9.0 percent (95 percent CI, 7.6 to 10.6 percent), and the risk of reoperation was 23.8 percent (95 percent CI, 21.8 to 26.0 percent). Over 99 percent of surgeons reported satisfaction with the postoperative results, and subject satisfaction remained high 5 years after implantation. The 5-year results of Sientra's study continue to provide a comprehensive safety and effectiveness profile of Sientra's portfolio of Silimed brand shaped and round implants. Therapeutic, IV.

  10. Rapid microwave-assisted synthesis of dextran-coated iron oxide nanoparticles for magnetic resonance imaging.

    Science.gov (United States)

    Osborne, Elizabeth A; Atkins, Tonya M; Gilbert, Dustin A; Kauzlarich, Susan M; Liu, Kai; Louie, Angelique Y

    2012-06-01

    Currently, magnetic iron oxide nanoparticles are the only nanosized magnetic resonance imaging (MRI) contrast agents approved for clinical use, yet commercial manufacturing of these agents has been limited or discontinued. Though there is still widespread demand for these particles both for clinical use and research, they are difficult to obtain commercially, and complicated syntheses make in-house preparation unfeasible for most biological research labs or clinics. To make commercial production viable and increase accessibility of these products, it is crucial to develop simple, rapid and reproducible preparations of biocompatible iron oxide nanoparticles. Here, we report a rapid, straightforward microwave-assisted synthesis of superparamagnetic dextran-coated iron oxide nanoparticles. The nanoparticles were produced in two hydrodynamic sizes with differing core morphologies by varying the synthetic method as either a two-step or single-step process. A striking benefit of these methods is the ability to obtain swift and consistent results without the necessity for air-, pH- or temperature-sensitive techniques; therefore, reaction times and complex manufacturing processes are greatly reduced as compared to conventional synthetic methods. This is a great benefit for cost-effective translation to commercial production. The nanoparticles are found to be superparamagnetic and exhibit properties consistent for use in MRI. In addition, the dextran coating imparts the water solubility and biocompatibility necessary for in vivo utilization.

  11. Rapid microwave-assisted synthesis of dextran-coated iron oxide nanoparticles for magnetic resonance imaging

    International Nuclear Information System (INIS)

    Osborne, Elizabeth A; Atkins, Tonya M; Kauzlarich, Susan M; Gilbert, Dustin A; Liu Kai; Louie, Angelique Y

    2012-01-01

    Currently, magnetic iron oxide nanoparticles are the only nanosized magnetic resonance imaging (MRI) contrast agents approved for clinical use, yet commercial manufacturing of these agents has been limited or discontinued. Though there is still widespread demand for these particles both for clinical use and research, they are difficult to obtain commercially, and complicated syntheses make in-house preparation unfeasible for most biological research labs or clinics. To make commercial production viable and increase accessibility of these products, it is crucial to develop simple, rapid and reproducible preparations of biocompatible iron oxide nanoparticles. Here, we report a rapid, straightforward microwave-assisted synthesis of superparamagnetic dextran-coated iron oxide nanoparticles. The nanoparticles were produced in two hydrodynamic sizes with differing core morphologies by varying the synthetic method as either a two-step or single-step process. A striking benefit of these methods is the ability to obtain swift and consistent results without the necessity for air-, pH- or temperature-sensitive techniques; therefore, reaction times and complex manufacturing processes are greatly reduced as compared to conventional synthetic methods. This is a great benefit for cost-effective translation to commercial production. The nanoparticles are found to be superparamagnetic and exhibit properties consistent for use in MRI. In addition, the dextran coating imparts the water solubility and biocompatibility necessary for in vivo utilization. (paper)

  12. Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage

    DEFF Research Database (Denmark)

    Holm, C; Thomsen, L L; Norgaard, A

    2017-01-01

    BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open-label, ran......BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open...

  13. Genetics Home Reference: iron-refractory iron deficiency anemia

    Science.gov (United States)

    ... refractory iron deficiency anemia Iron-refractory iron deficiency anemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

  14. Iron Test

    Science.gov (United States)

    ... 793, 826-827. Harmening D, Clinical Hematology and Fundamentals of Hemostasis, Fifth Edition, F.A. Davis Company, ... htm. Accessed June 2009. Henry's Clinical Diagnosis and Management by Laboratory Methods . 21st ed. McPherson RA and ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... increased need for iron during growth spurts. Older adults, especially those over age ... athletes. Athletes, especially young females, are at risk for iron deficiency. Endurance ...

  16. Iron and stony-iron meteorites

    DEFF Research Database (Denmark)

    Benedix, Gretchen K.; Haack, Henning; McCoy, T. J.

    2014-01-01

    Without iron and stony-iron meteorites, our chances of ever sampling the deep interior of a differentiated planetary object would be next to nil. Although we live on a planet with a very substantial core, we will never be able to sample it. Fortunately, asteroid collisions provide us with a rich...... sampling of the deep interiors of differentiated asteroids. Iron and stony-iron meteorites are fragments of a large number of asteroids that underwent significant geological processing in the early solar system. Parent bodies of iron and some stony-iron meteorites completed a geological evolution similar...... to that continuing on Earth – although on much smaller length- and timescales – with melting of the metal and silicates; differentiation into core, mantle, and crust; and probably extensive volcanism. Iron and stony-iron meteorites are our only available analogues to materials found in the deep interiors of Earth...

  17. Iron overload in myelodysplastic syndromes (MDS).

    Science.gov (United States)

    Gattermann, Norbert

    2018-01-01

    Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

  18. Iron from Zealandic bog iron ore -

    DEFF Research Database (Denmark)

    Lyngstrøm, Henriette Syrach

    2011-01-01

    og geologiske materiale, metallurgiske analyser og eksperimentel arkæologiske forsøg - konturerne af en jernproduktion med udgangspunkt i den sjællandske myremalm. The frequent application by archaeologists of Werner Christensen’s distribution map for the occurrence of bog iron ore in Denmark (1966...... are sketched of iron production based on bog iron ore from Zealand....

  19. Native iron

    DEFF Research Database (Denmark)

    Brooks, Charles Kent

    2015-01-01

    System, was reduced. The oxidized outer layers of the Earth have formed by two processes. Firstly, water is decomposed to oxygen and hydrogen by solar radiation in the upper parts of the atmosphere, the light hydrogen diffusing to space, leaving oxygen behind. Secondly, plants, over the course......, hematite, or FeO.Fe2O3, magnetite), with carbon in the form of coke. This is carried out in a blast furnace. Although the Earth's core consists of metallic iron, which may also be present in parts of the mantle, this is inaccessible to us, so we must make our own. In West Greenland, however, some almost......We live in an oxidized world: oxygen makes up 22 percent of the atmosphere and by reacting with organic matter produces most of our energy, including the energy our bodies use to function: breathe, think, move, etc. It has not always been thus. Originally the Earth, in common with most of the Solar...

  20. Comparative studies on the human serum albumin binding of the clinically approved EGFR inhibitors gefitinib, erlotinib, afatinib, osimertinib and the investigational inhibitor KP2187.

    Science.gov (United States)

    Dömötör, Orsolya; Pelivan, Karla; Borics, Attila; Keppler, Bernhard K; Kowol, Christian R; Enyedy, Éva A

    2018-05-30

    Binding interactions between human serum albumin (HSA) and four approved epidermal growth factor receptor (EGFR) inhibitors gefitinib (GEF), erlotinib (ERL), afatinib (AFA), osimertinib (OSI), as well as the experimental drug KP2187, were investigated by means of spectrofluorometric and molecular modelling methods. Steady-state and time resolved spectrofluorometric techniques were carried out, including direct quenching of protein fluorescence and site marker displacement measurements. Proton dissociation processes and solvent dependent fluorescence properties were investigated as well. The EGFR inhibitors were predominantly presented in their single protonated form (HL + ) at physiological pH except ERL, which is charge-neutral. Significant solvent dependent fluorescence properties were found for GEF, ERL and KP2187, namely their emission spectra show strong dependence on the polarity and the hydrogen bonding ability of the solvents. The inhibitors proved to be bound at site I of HSA (in subdomain IIA) in a weak-to-moderate fashion (logK' 3.9-4.9) using spectrofluorometry. OSI (logK' 4.3) and KP2187 can additionally bind in site II (in subdomain IIIA), while GEF, ERL and AFA clearly show no interaction here. Docking methods qualitatively confirmed binding site preferences of compounds GEF and KP2187, and indicated that they probably bind to HSA in their neutral forms. Binding constants calculated on the basis of the various experimental data indicate a weak-to-moderate binding on HSA, only OSI exhibits somewhat higher affinity towards this protein. However, model calculations performed at physiological blood concentrations of HSA resulted in high (ca. 90%) bound fractions for the inhibitors, highlighting the importance of plasma protein binding. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Intravenous Iron Therapy in Patients with Iron Deficiency Anemia: Dosing Considerations

    Directory of Open Access Journals (Sweden)

    Todd A. Koch

    2015-01-01

    Full Text Available Objective. To provide clinicians with evidence-based guidance for iron therapy dosing in patients with iron deficiency anemia (IDA, we conducted a study examining the benefits of a higher cumulative dose of intravenous (IV iron than what is typically administered. Methods. We first individually analyzed 5 clinical studies, averaging the total iron deficit across all patients utilizing a modified Ganzoni formula; we then similarly analyzed 2 larger clinical studies. For the second of the larger studies (Study 7, we also compared the efficacy and retreatment requirements of a cumulative dose of 1500 mg ferric carboxymaltose (FCM to 1000 mg iron sucrose (IS. Results. The average iron deficit was calculated to be 1531 mg for patients in Studies 1–5 and 1392 mg for patients in Studies 6-7. The percentage of patients who were retreated with IV iron between Days 56 and 90 was significantly (p<0.001 lower (5.6% in the 1500 mg group, compared to the 1000 mg group (11.1%. Conclusions. Our data suggests that a total cumulative dose of 1000 mg of IV iron may be insufficient for iron repletion in a majority of patients with IDA and a dose of 1500 mg is closer to the actual iron deficit in these patients.

  2. Impact of iron overload and potential benefit from iron chelation in low-risk myelodysplastic syndrome.

    Science.gov (United States)

    Shenoy, Niraj; Vallumsetla, Nishanth; Rachmilewitz, Eliezer; Verma, Amit; Ginzburg, Yelena

    2014-08-07

    Myelodysplastic syndromes (MDSs) are a group of heterogeneous clonal bone marrow disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and potential for malignant transformation. Lower/intermediate-risk MDSs are associated with longer survival and high red blood cell (RBC) transfusion requirements resulting in secondary iron overload. Recent data suggest that markers of iron overload portend a relatively poor prognosis, and retrospective analysis demonstrates that iron chelation therapy is associated with prolonged survival in transfusion-dependent MDS patients. New data provide concrete evidence of iron's adverse effects on erythroid precursors in vitro and in vivo. Renewed interest in the iron field was heralded by the discovery of hepcidin, the main serum peptide hormone negative regulator of body iron. Evidence from β-thalassemia suggests that regulation of hepcidin by erythropoiesis dominates regulation by iron. Because iron overload develops in some MDS patients who do not require RBC transfusions, the suppressive effect of ineffective erythropoiesis on hepcidin may also play a role in iron overload. We anticipate that additional novel tools for measuring iron overload and a molecular-mechanism-driven description of MDS subtypes will provide a deeper understanding of how iron metabolism and erythropoiesis intersect in MDSs and improve clinical management of this patient population. © 2014 by The American Society of Hematology.

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... blocks the intestine from taking up iron. Other medical conditions Other medical conditions that may lead to iron-deficiency anemia ... daily amount of iron. If you have other medical conditions that cause iron-deficiency anemia , such as ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español ... bleeding Consuming less than recommended daily amounts of iron Iron-deficiency anemia can be caused by getting ...

  5. Serum iron test

    Science.gov (United States)

    Fe+2; Ferric ion; Fe++; Ferrous ion; Iron - serum; Anemia - serum iron; Hemochromatosis - serum iron ... A blood sample is needed. Iron levels are highest in the morning. Your health care provider will likely have you do this test in the morning.

  6. Nutritional iron deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.; Hurrell, R.F.

    2007-01-01

    Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estimated 2 billion people. Nutritional iron deficiency arises when physiological requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations consuming

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... peas, tofu, dried fruits, and dark green leafy vegetables. Foods rich in vitamin C, such as oranges, strawberries, ... iron are meat, poultry, fish, and iron-fortified foods that have iron ... green leafy vegetables. You can also take an iron supplement. Follow ...

  8. Iron deficiency anemia

    Science.gov (United States)

    Anemia - iron deficiency ... iron from old red blood cells. Iron deficiency anemia develops when your body's iron stores run low. ... You may have no symptoms if the anemia is mild. Most of the time, ... slowly. Symptoms may include: Feeling weak or tired more often ...

  9. Iron Administration before Stem Cell Harvest Enables MR Imaging Tracking after Transplantation

    OpenAIRE

    Khurana, Aman; Chapelin, Fanny; Beck, Graham; Lenkov, Olga D.; Donig, Jessica; Nejadnik, Hossein; Messing, Solomon; Derugin, Nikita; Chan, Ray Chun-Fai; Gaur, Amitabh; Sennino, Barbara; McDonald, Donald M.; Kempen, Paul J.; Tikhomirov, Grigory A.; Rao, Jianghong

    2013-01-01

    Transplanted mesenchymal stem cells (MSCs) could be detected and tracked with MR imaging, if the donor is treated with an intravenous injection of the Food and Drug Administration–approved iron supplement ferumoxytol prior to MSC harvesting.

  10. The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Katrina Tatton-Brown

    2018-04-01

    Full Text Available Tatton-Brown-Rahman syndrome (TBRS; OMIM 615879, also known as the DNMT3A-overgrowth syndrome, is an overgrowth intellectual disability syndrome first described in 2014 with a report of 13 individuals with constitutive heterozygous DNMT3A variants. Here we have undertaken a detailed clinical study of 55 individuals with de novo DNMT3A variants, including the 13 previously reported individuals. An intellectual disability and overgrowth were reported in >80% of individuals with TBRS and were designated major clinical associations. Additional frequent clinical associations (reported in 20-80% individuals included an evolving facial appearance with low-set, heavy, horizontal eyebrows and prominent upper central incisors; joint hypermobility (74%; obesity (weight ³2SD, 67%; hypotonia (54%; behavioural/psychiatric issues (most frequently autistic spectrum disorder, 51%; kyphoscoliosis (33% and afebrile seizures (22%. One individual was diagnosed with acute myeloid leukaemia in teenage years. Based upon the results from this study, we present our current management for individuals with TBRS

  11. Iron absorption in relation to iron status

    International Nuclear Information System (INIS)

    Magnusson, B.; Bjoern-Rasmussen, E.; Hallberg, L.; Rossander, L.

    1981-01-01

    The absorption from a 3 mg dose of ferrous iron was measured in 250 male subjects. The absorption was related to the log concentration of serum ferritin in 186 subjects of whom 99 were regular blood donors (r= -0.76), and to bone marrow haemosiderin grading in 52 subjects with varying iron status. The purpose was to try and establish a percentage absorption from such a dose that is representative of subjects who are borderline iron deficient. This information is necessary for food iron absorption studies in order (1) to calculate the absorption of iron from the diet at a given iron status and (2) compare the absorption of iron from different meals studied in different groups of subjects by different investigarors. The results suggest that an absorption of about 40% of a 3 mg reference dose of ferrous iron is given in a fasting state, roughly corresponds to the absorption in borderline-iron-deficient subjects. The results indicate that this 40% absorption value corresponds to a serum ferritin level of 30 μg/l and that food iron absorption in a group of subjects should be expressed preferably as the absorption corresponding to a reference-dose absorption of 45%, or possibly a serum ferritin level of 30 μg/l. (author)

  12. Effect of iron on expression of efflux pump (adeABC) and quorum sensing (luxI, luxR) genes in clinical isolates of Acinetobacter baumannii.

    Science.gov (United States)

    Modarresi, Farzan; Azizi, Omid; Shakibaie, Mohammad Reza; Motamedifar, Mohammad; Valibeigi, Behnaz; Mansouri, Shahla

    2015-11-01

    Resistance-nodulation-division efflux system (RND) adeABC contributes to intrinsic resistance to various drug classes in Acinetobacter baumannii. Similarly, quorum sensing (QS) plays an important role in the biofilm formation and pathogenicity of this bacterium. The aims of this study were to evaluate the influence of iron limitation on the expression of efflux pump (adeABC) genes and QS (luxI, luxR) system by relative quantitative real-time polymerase chain reaction (qRT-PCR). In addition, DNA sequence and phylogenetic relatedness of biofilm-associated protein (Bap) gene was also investigated. Sixty-five multidrug-resistant isolates of A. baumannii were recovered from ICU patients of three hospitals in Kerman, Iran. The isolates were highly resistant to at least 11 antibiotics (MIC ≥64 μg/mL); however, 87% and 89% were susceptible to colistin and tigecycline, respectively (MIC 0.05 μg/mL) (p ≤ 0.05). We detected the presence of RND efflux pump, QS, and bap genes with the frequencies of 92% (adeA), 61.5% (adeB), 84.6% (adeC), 80% (luxI), 61% (luxR), and 66% (bap), respectively. qRT-PCR analysis showed that in some isolates, expression of both adeABC and luxI/R was increased more than fourfold in the presence of low iron (20 μm), suggesting the additional regulatory role of iron on both efflux pump and QS system. Alignment and phylogenetic analysis on the strong biofilm forming isolates confirmed that the fragments amplified were indeed part of bap gene and deduced sequence was similar to A. baumannii K9B410. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  13. Drugs Approved for Thyroid Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Thyroid Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Thyroid Cancer Cabozantinib-S-Malate Caprelsa (Vandetanib) Cometriq (Cabozantinib-S-Malate) Doxorubicin ...

  14. Drugs Approved for Breast Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Breast Cancer This page lists cancer drugs approved by the ... are not listed here. Drugs Approved to Prevent Breast Cancer Evista (Raloxifene Hydrochloride) Raloxifene Hydrochloride Tamoxifen Citrate Drugs ...

  15. Electronic medical records in humanitarian emergencies – the development of an Ebola clinical information and patient management system [version 3; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Kiran Jobanputra

    2017-02-01

    Full Text Available By November 2015, the West Africa Ebola epidemic had caused 28598 infections and 11299 deaths in the three countries most affected. The outbreak required rapid innovation and adaptation. Médecins sans Frontières (MSF scaled up its usual 20-30 bed Ebola management centres (EMCs to 100-300 beds with over 300 workers in some settings. This brought challenges in patient and clinical data management resulting from the difficulties of working safely with high numbers of Ebola patients. We describe a project MSF established with software developers and the Google Social Impact Team to develop context-adapted tools to address the challenges of recording Ebola clinical information. We share the outcomes and key lessons learned in innovating rapidly under pressure in difficult environmental conditions. Information on adoption, maintenance, and data quality was gathered through review of project documentation, discussions with field staff and key project stakeholders, and analysis of tablet data. In March 2015, a full prototype was deployed in Magburaka EMC, Sierra Leone. Inpatient data were captured on 204 clinical interactions with 34 patients from 5 March until 10 April 2015. Data continued to also be recorded on paper charts, creating theoretically identical record “pairs” on paper and tablet. 83 record pairs for 33 patients with 22 data items (temperature and symptoms per pair were analysed. The overall Kappa coefficient for agreement between sources was 0.62, but reduced to 0.59 when rare bleeding symptoms were excluded, indicating moderate to good agreement. The time taken to deliver the product was more than that anticipated by MSF (7 months versus 6 weeks. Deployment of the tablet coincided with a dramatic drop in patient numbers and thus had little impact on patient care. We have identified lessons specific to humanitarian-technology collaborative projects and propose a framework for emergency humanitarian innovation. Time and effort is

  16. Iron deficiency anaemia: with the conclusion of a need for iron reader

    Science.gov (United States)

    Lim, Wai Feng; Yap, Boon Kar; Lai, Mei I.; Talik, Noorazrina; Nasser, Ammar Ahmed; Al-Haiqi, Ahmed Mubarak Ahmed; Sankar Krishnan, Prajindra

    2017-10-01

    In our bloodstream, there are plenty of red blood cells (RBC), which function as an important oxygen carrier in our bodies. Each RBC consists of millions of haemoglobin (Hb), which is made up from globin and iron. If any deficiency/malfunction of any globin, it will lead to anaemia as indicated in low Hb level while iron deficiency anaemia (IDA) is anaemic due to the lacking of iron as indicated in low Hb and ferritin levels. IDA affects almost two billion people globally while anaemia without iron deficiency, such as thalassaemia, affects almost 4.5% in Malaysian population. These anaemic conditions have similar clinical symptoms like fatigue, dizziness, in which disturb their cognitive development and productivity in workplace. In areas without proper medical access, many anaemic individuals were misdiagnosed and treated with iron tablets because they were thought to have iron deficiency anaemia due to low Hb content. But, excess iron is toxic to the body. Misdiagnosis can be avoided by iron status assessment. We hereby review the currently available iron status parameters in laboratory and field study with the conclusion of demonstrating the importance of a need for iron reader, in the effort to reduce the prevalence of IDA globally.

  17. The effect of a health literacy approach to counselling on the lifestyle of women with gestational diabetes: A clinical trial [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Mehrafza Gharachourlo

    2018-03-01

    Full Text Available Background: Gestational diabetes is a common pregnancy disorder that affects the mother’s and neonate’s health. The present study was conducted to investigate the effect of a health literacy approach to counselling on the lifestyle of women with gestational diabetes. The present randomized controlled clinical trial was conducted in 2017 using a parallel design. The subjects included 84 eligible women presenting to Alborz and Kamali Hospitals, Karaj, Iran. Methods: Convenience sampling was first used to select the subjects. They were then assigned to an intervention or control group based on randomized blocks of four. Both groups attended counselling sessions. The mothers in the intervention group attended six sessions of counselling with a health literacy approach in addition to counselling on routine pregnancy care. The control group attended counselling sessions on safe pregnancy care and received a training package containing all the subjects discussed in the intervention group. The Lifestyle Questionnaire and the Iranian Health Literacy Questionnaire were completed by the mothers at the beginning and at the end of the sessions as well as three weeks after the sessions. The data obtained were analyzed in SPSS-19. Results: According to the study findings, the scores of lifestyle (P=0.8 and health literacy (P=0.423 showed no significant differences between the intervention and control groups before the intervention. Significant differences were, however, observed in the mean scores of lifestyle and health literacy between the two groups immediately and three weeks after the intervention. Comparing the means showed a higher increase in the mean scores in the intervention group (P<0.001. Conclusions: Providing counselling services by midwives can significantly help modify mothers’ unhealthy lifestyle choices and increase their health literacy; therefore, reducing maternal and neonatal consequences, especially in high-risk pregnancies. Trial

  18. Using data from a multi-hospital clinical network to explore prevalence of pediatric rickets in Kenya [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Stella W. Karuri

    2017-08-01

    Full Text Available Background: Nutritional rickets is a public health concern in developing countries despite tropical climates and a re-emerging issue in developed countries. In this study, we reviewed pediatric admission data from the Clinical Information Network (CIN to help determine hospital and region based prevalence of rickets in three regions of Kenya (Central Kenya, Western Kenya and Nairobi County. We also examine the association of rickets with other diagnosis, such as malnutrition and pneumonia, and study the effect of rickets on regional hospital stays. Methods: We analyzed discharge records for children aged 1 month to 5 years from county (formerly district hospitals in the CIN, with admissions from February 1st 2014 to February 28th 2015. The strength of the association between rickets and key demographic factors, as well as with malnutrition and pneumonia, was assessed using odds ratios. The Fisher exact test was used to test the significance of the estimated odd ratios. Kaplan-Meier curves were used to analyze length of hospital stays. Results: There was a marked difference in prevalence across the three regions, with Nairobi having the highest number of cases of rickets at a proportion of 4.01%, followed by Central Region at 0.92%. Out of 9756 admissions in the Western Region, there was only one diagnosis of rickets. Malnutrition was associated with rickets; this association varied regionally. Pneumonia was found to be associated with rickets in Central Kenya. Children diagnosed with rickets had longer hospital stays, even when cases of malnutrition and pneumonia were excluded in the analysis. Conclusion: There was marked regional variation in hospital based prevalence of rickets, but in some regions it is a common clinical diagnosis suggesting the need for targeted public health interventions. Factors such as maternal and child nutrition, urbanization and cultural practices might explain these differences.

  19. Integrated analysis of oral tongue squamous cell carcinoma identifies key variants and pathways linked to risk habits, HPV, clinical parameters and tumor recurrence [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Neeraja Krishnan

    2015-11-01

    Full Text Available Oral tongue squamous cell carcinomas (OTSCC are a homogeneous group of tumors characterized by aggressive behavior, early spread to lymph nodes and a higher rate of regional failure. Additionally, the incidence of OTSCC among younger population (<50yrs is on the rise; many of whom lack the typical associated risk factors of alcohol and/or tobacco exposure. We present data on single nucleotide variations (SNVs, indels, regions with loss of heterozygosity (LOH, and copy number variations (CNVs from fifty-paired oral tongue primary tumors and link the significant somatic variants with clinical parameters, epidemiological factors including human papilloma virus (HPV infection and tumor recurrence. Apart from the frequent somatic variants harbored in TP53, CASP8, RASA1, NOTCH and CDKN2A genes, significant amplifications and/or deletions were detected in chromosomes 6-9, and 11 in the tumors. Variants in CASP8 and CDKN2A were mutually exclusive. CDKN2A, PIK3CA, RASA1 and DMD variants were exclusively linked to smoking, chewing, HPV infection and tumor stage. We also performed a whole-genome gene expression study that identified matrix metalloproteases to be highly expressed in tumors and linked pathways involving arachidonic acid and NF-k-B to habits and distant metastasis, respectively. Functional knockdown studies in cell lines demonstrated the role of CASP8 in a HPV-negative OTSCC cell line. Finally, we identified a 38-gene minimal signature that predicts tumor recurrence using an ensemble machine-learning method. Taken together, this study links molecular signatures to various clinical and epidemiological factors in a homogeneous tumor population with a relatively high HPV prevalence.

  20. Using data from a multi-hospital clinical network to explore prevalence of pediatric rickets in Kenya [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Stella W. Karuri

    2017-11-01

    Full Text Available Background: Nutritional rickets is a public health concern in developing countries despite tropical climates and a re-emerging issue in developed countries. In this study, we reviewed pediatric admission data from the Clinical Information Network (CIN to help determine hospital and region based prevalence of rickets in three regions of Kenya (Central Kenya, Western Kenya and Nairobi County. We also examine the association of rickets with other diagnosis, such as malnutrition and pneumonia, and study the effect of rickets on regional hospital stays. Methods: We analyzed discharge records for children aged 1 month to 5 years from county (formerly district hospitals in the CIN, with admissions from February 1st 2014 to February 28th 2015. The strength of the association between rickets and key demographic factors, as well as with malnutrition and pneumonia, was assessed using odds ratios. The Fisher exact test was used to test the significance of the estimated odd ratios. Kaplan-Meier curves were used to analyze length of hospital stays. Results: There was a marked difference in prevalence across the three regions, with Nairobi having the highest number of cases of rickets at a proportion of 4.01%, followed by Central Region at 0.92%. Out of 9756 admissions in the Western Region, there was only one diagnosis of rickets. Malnutrition was associated with rickets; this association varied regionally. Pneumonia was found to be associated with rickets in Central Kenya. Children diagnosed with rickets had longer hospital stays, even when cases of malnutrition and pneumonia were excluded in the analysis. Conclusion: There was marked regional variation in hospital based prevalence of rickets, but in some regions it is a common clinical diagnosis suggesting the need for targeted public health interventions. Factors such as maternal and child nutrition, urbanization and cultural practices might explain these differences.

  1. Radiological Medical Device Innovation: Approvals via the Premarket Approval Pathway From 2000 to 2015.

    Science.gov (United States)

    Ghobadi, Comeron W; Hayman, Emily L; Finkle, Joshua H; Walter, Jessica R; Xu, Shuai

    2017-01-01

    The aim of this study was to critically assess the clinical evidence leading to radiologic medical device approvals via the premarket approval pathway from 2000 to 2015. This study used the publically available FDA premarket database for radiologic device approvals over the past 15 years (September 1, 2000, to August 31, 2015). Approval characteristics were collected for each device, and statistical analysis was performed on the data for each pivotal trial. Additionally, methodological quality of the pivotal trial was determined using the Quality Assessment of Diagnostic Accuracy Studies tool. Twenty-three class III radiologic device approvals were identified, with breast imaging accounting for 16 (70%) and computer-aided detection software accounting for 9 (39%) approvals. The median premarket approval time was 475 days (range, 180-1,116). Twenty-one devices were approved on the basis of multireader, multicenter studies, one on the basis of a randomized controlled trial, and one on the basis of a preclinical technical equivalence trial. The median number of patients per pivotal trial was 201 (range, 25-3,946). Twenty-six of the 34 pivotal trials (76%) had at least one methodologic bias. Breast imaging devices had a greater number of patients per pivotal trial (P = .009) and more prospective studies. With regard to all modalities, increased time to device approval correlated with weaker trial quality (r = 0.600, P assessing diagnostic technologies. Given that radiologic devices play a key role in modern medicine, further efforts should be made to increase transparency of clinical data leading to approval. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  2. Evaluation of a new tablet formulation of deferasirox to reduce chronic iron overload after long-term blood transfusions

    Directory of Open Access Journals (Sweden)

    Chalmers AW

    2016-02-01

    Full Text Available Anna W Chalmers, Jamile M Shammo Department of Internal Medicine, Division of Hematology/Oncology, Rush University Medical Center, Chicago, IL, USA Abstract: Transfusion-dependent anemia is a common feature in a wide array of hematological disorders, including thalassemia, sickle cell disease, aplastic anemia, myelofibrosis, and myelodysplastic syndromes. In the absence of a physiological mechanism to excrete excess iron, chronic transfusions ultimately cause iron overload. Without correction, iron overload can lead to end-organ damage, resulting in cardiac, hepatic, and endocrine dysfunction/failure. Iron chelating agents are utilized to reduce iron overload, as they form a complex with iron, leading to its clearance. Iron chelation has been proven to decrease organ dysfunction and improve survival in certain transfusion-dependent anemias, such as β-thalassemia. Several chelating agents have been approved by the United States Food and Drug Administration for the treatment of iron overload, including deferoxamine, deferiprone, and deferasirox. A variety of factors have to be considered when choosing an iron chelator, including dosing schedule, route of administration, tolerability, and side effect profile. Deferasirox is an orally administered iron chelator with proven efficacy and safety in multiple hematological disorders. There are two formulations of deferasirox, a tablet for suspension, and a new tablet form. This paper is intended to provide an overview of iron overload, with a focus on deferasirox, and its recently approved formulation Jadenu® for the reduction of transfusional iron overload in hematological disorders. Keywords: iron chelation therapy, transfusional iron overload, deferasirox

  3. Heart failure in patients with kidney disease and iron deficiency; the role of iron therapy.

    Science.gov (United States)

    Cases Amenós, Aleix; Ojeda López, Raquel; Portolés Pérez, José María

    Chronic kidney disease and anaemia are common in heart failure (HF) and are associated with a worse prognosis in these patients. Iron deficiency is also common in patients with HF and increases the risk of morbidity and mortality, regardless of the presence or absence of anaemia. While the treatment of anaemia with erythropoiesis-stimulating agents in patients with HF have failed to show a benefit in terms of morbidity and mortality, treatment with IV iron in patients with HF and reduced ejection fraction and iron deficiency is associated with clinical improvement. In a posthoc analysis of a clinical trial, iron therapy improved kidney function in patients with HF and iron deficiency. In fact, the European Society of Cardiology's recent clinical guidelines on HF suggest that in symptomatic patients with reduced ejection fraction and iron deficiency, treatment with IV ferric carboxymaltose should be considered to improve symptoms, the ability to exercise and quality of life. Iron plays a key role in oxygen storage (myoglobin) and in energy metabolism, and there are pathophysiological bases that explain the beneficial effect of IV iron therapy in patients with HF. All these aspects are reviewed in this article. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  4. Poet Marion Approval

    Science.gov (United States)

    This update August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-North Manchester, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable

  5. Poet Portland Approval

    Science.gov (United States)

    This update August 9, 2016 letter from EPA approves the petition, with modifications, from Poet Biorefining-Portland, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel

  6. Poet North Manchester Approval

    Science.gov (United States)

    This update August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-North Manchester, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable

  7. Poet Alexandria Approval

    Science.gov (United States)

    This update August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-Alexandria, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel

  8. Poet Laddonia Approval

    Science.gov (United States)

    This update Auugust 9, 2016 letter from EPA approves with modifications, the petition from Poet Biorefining Laddonia, Poet Laddonia Facility, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act f

  9. Drugs Approved for Neuroblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  10. Drugs Approved for Leukemia

    Science.gov (United States)

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  11. Drugs Approved for Retinoblastoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  12. Premarket Approvals (PMA)

    Data.gov (United States)

    U.S. Department of Health & Human Services — Premarket approval by FDA is the required process of scientific review to ensure the safety and effectiveness of all devices classified as Class III devices. An...

  13. Iron Supplementation, Response in Iron-Deficiency Anemia: Analysis of Five Trials.

    Science.gov (United States)

    Okam, Maureen M; Koch, Todd A; Tran, Minh-Ha

    2017-08-01

    Oral iron-replacement therapy is the mainstay of treatment for iron-deficiency anemia, but it is often poorly tolerated or ineffective. Hemoglobin response at day 14 of oral iron may be useful in assessing whether and when to transition patients from oral to intravenous (IV) iron. Pooled data from 5 randomized trials were analyzed to compare oral and IV iron-replacement therapy for iron-deficiency anemia. Treatment criteria and assignment to oral versus IV iron were defined per protocol; this analysis included only subjects receiving oral iron. Responders were subjects with ≥1.0-g/dL increases in hemoglobin at day 14, and nonresponders were those with smaller increases. Demographic and clinical characteristics were evaluated for association with hemoglobin response at multiple timepoints. Most subjects (72.8%) were classified as responders. The proportion of subjects with hemoglobin increases ≥1.0, ≥2.0, and ≥3.0 g/dL was greatest among those with postpartum anemia, intermediate among those with heavy uterine bleeding or gastrointestinal-related causes of anemia, and lowest among those with other causes; this proportion was also significantly greater among responders than nonresponders. A ≥1.0-g/dL increase in hemoglobin on day 14 most accurately predicted satisfactory overall hemoglobin response to oral iron on day 42/56 (sensitivity 90.1%; specificity 79.3%; positive and negative predictive values of 92.9% and 72.7%, respectively). Iron-replacement therapy improved quality of life and reduced fatigue. Hemoglobin responses <1.0 g/dL at day 14 of oral iron identify subjects with iron-deficiency anemia who should be transitioned to IV iron supplementation. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Air pollution particles and iron homeostasis | Science ...

    Science.gov (United States)

    Background: The mechanism underlying biological effects of particles deposited in the lung has not been defined. Major Conclusions: A disruption in iron homeostasis follows exposure of cells to all particulate matter including air pollution particles. Following endocytosis, functional groups at the surface of retained particle complex iron available in the cell. In response to a reduction in concentrations of requisite iron, a functional deficiency can result intracellularly. Superoxide production by the cell exposed to a particle increases ferrireduction which facilitates import of iron with the objective being the reversal of the metal deficiency. Failure to resolve the functional iron deficiency following cell exposure to particles activates kinases and transcription factors resulting in a release of inflammatory mediators and inflammation. Tissue injury is the end product of this disruption in iron homeostasis initiated by the particle exposure. Elevation of available iron to the cell precludes deficiency of the metal and either diminishes or eliminates biological effects.General Significance: Recognition of the pathway for biological effects after particle exposure to involve a functional deficiency of iron suggests novel therapies such as metal supplementation (e.g. inhaled and oral). In addition, the demonstration of a shared mechanism of biological effects allows understanding the common clinical, physiological, and pathological presentation fol

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... fatigue or tiredness, shortness of breath, or chest pain. If your doctor diagnoses you with iron-deficiency ... Common symptoms of iron-deficiency anemia include: Chest pain Coldness in the hands and feet Difficulty concentrating ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... body to absorb iron from the gastrointestinal tract (GI tract). Blood loss When you lose blood, you ... to iron-deficiency anemia include: Bleeding in your GI tract, from an ulcer, colon cancer, or regular ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... complications, including heart failure and development delays in children. Explore this Health ... red blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... heart failure . Increased risk of infections Motor or cognitive development delays in children Pregnancy complications, such as ... for iron-deficiency anemia. Learn about exciting research areas that NHLBI is exploring about iron-deficiency anemia. ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Health and Human Development, we are investigating how best to treat premature newborns with low hemoglobin levels. ... are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children who ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... your doctor may recommend changes to help you meet the recommended daily amount of iron. If you ... stop bleeding. Healthy lifestyle changes To help you meet your daily recommended iron levels, your doctor may ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... an MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such ... drinking black tea, which reduces iron absorption. Other treatments If you have chronic kidney disease and iron- ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... same for boys and girls. From birth to 6 months, babies need 0.27 mg of iron. ... for iron deficiency at certain ages: Infants between 6 and 12 months, especially if they are fed ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... your blood may be normal even if the total amount of iron in your body is low. ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... of the condition. Your doctor may recommend healthy eating changes, iron supplements, intravenous iron therapy for mild ... less Look for Treatment will discuss medicines and eating pattern changes that your doctors may recommend if ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Disorders Lung Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and ... lose blood, you lose iron. Certain conditions or medicines can cause blood loss and lead to iron- ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... absorb iron and lead to iron-deficiency anemia. These conditions include: Intestinal and digestive conditions, such as ... tract. Inflammation from congestive heart failure or obesity . These chronic conditions can lead to inflammation that may ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... C to help your body absorb iron. Avoid drinking black tea, which reduces iron absorption. Other treatments ... improve health through research and scientific discovery. Improving health with current research Learn about the following ways ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... higher risk, as most of a newborn’s iron stores are developed during the third trimester of pregnancy. ... red blood cells on hand, their bodies can store iron to prepare for blood loss during delivery. ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... may be diagnosed with iron-deficiency anemia if you have low iron or ferritin levels in your blood. More testing may be needed to rule out other types of anemia. Tests for gastrointestinal ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... were born prematurely may be at an even higher risk, as most of a newborn’s iron stores ... men of the same age. Women are at higher risk for iron-deficiency anemia under some circumstances, ...

  11. Iron supplements (image)

    Science.gov (United States)

    The mineral iron is an essential nutrient for humans because it is part of blood cells, which carry oxygen to all body cells. There is no conclusive evidence that iron supplements contribute to heart attacks.

  12. Total iron binding capacity

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003489.htm Total iron binding capacity To use the sharing features on this page, please enable JavaScript. Total iron binding capacity (TIBC) is a blood test to ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... may require intravenous (IV) iron therapy or a blood transfusion . Iron supplements Your doctor may recommend that you ... Anemia Aplastic Anemia Arrhythmia Blood Donation Blood Tests Blood Transfusion Heart-Healthy Lifestyle Changes Heart Failure Hemolytic Anemia ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron from the gastrointestinal tract (GI tract). Blood loss When you lose blood, you lose iron. Certain ... domestic small businesses that have strong potential for technology commercialization through the Small Business Innovation Research (SBIR) ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... also often take other medicines—such as proton pump inhibitors, anticoagulants, or blood thinners—that may cause iron-deficiency anemia. Proton pump inhibitors interfere with iron absorption, and blood thinners ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Look for Treatment will discuss medicines and eating pattern changes that your doctors may recommend if you ... iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... striking the ground, such as with marathon runners. Sex Girls and women between the ages of 14 ... developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron- ... factors , such as if you are following a vegetarian eating pattern, your doctor may recommend changes to ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... deficiency anemia. Proton pump inhibitors interfere with iron absorption, and blood thinners increase the likelihood of bleeding ... oranges, strawberries, and tomatoes, may help increase your absorption of iron. If you are pregnant, talk to ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Not eating enough iron-rich foods, such as meat and fish, may result in you getting less ... include dried beans, dried fruits, eggs, lean red meat, salmon, iron-fortified breads and cereals, peas, tofu, ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... mg and women need 18 mg. After age 51, both men and women need 8 mg. Pregnant ... for iron-deficiency anemia. Learn about exciting research areas that NHLBI is exploring about iron-deficiency anemia. ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia. These conditions include: Intestinal and digestive conditions, such as celiac disease; inflammatory bowel diseases, ... iron-deficiency anemia , such as bleeding in the digestive or urinary tract or heavy menstrual bleeding, your ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... prevent complications such as abnormal heart rhythms and depression. Learn the warning signs of serious complications and ... donors for low iron stores. Reliable point-of-care testing may help identify iron deficiency before potentially ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... breastfeeding women older than 18 need 9 mg. Problems absorbing iron Even if you consume the recommended ... interested in learning how having iron-deficiency anemia early in life affects later behavior, thinking, and mood ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ... the size of your liver and spleen. Blood tests Based on results from blood tests to screen ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... as most of a newborn’s iron stores are developed during the third trimester of pregnancy. Children between ... This makes it harder to stop bleeding and can increase the risk of iron-deficiency anemia from ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... have less hemoglobin than normal. Hemoglobin is a protein inside red blood cells that carries oxygen from ... stored iron has been used. Ferritin is a protein that helps store iron in your body. Reticulocyte ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and Strategic Vision Leadership Scientific Divisions Operations and Administration Advisory Committees Budget and Legislative Information Jobs and ... blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron is too ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in ... be hard to get the recommended amount from food alone. Pregnant women need more iron to support ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... learning how having iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... endoscopy or colonoscopy, to stop bleeding. Healthy lifestyle changes To help you meet your daily recommended iron ... iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... family history and genetics , lifestyle habits, or sex. Age You may be at increased risk for iron ... Signs, Symptoms, and Complications Iron-deficiency anemia can range from mild to severe. People with mild or ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... leaving cells where it is stored or from being absorbed in the duodenum, the first part of ... treatments for iron-deficiency anemia. Living With After being diagnosed with iron-deficiency anemia, it is important ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron to prepare for blood loss during delivery. Screening and Prevention Your doctor may screen you for ... and symptoms of iron-deficiency anemia. Return to Screening and Prevention to review tests to screen for ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Teens, who have increased need for iron during growth spurts. Older adults, especially those over age 65. ... need for iron increases during these periods of growth and development, and it may be hard to ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... endoscopy or colonoscopy, to stop bleeding. Healthy lifestyle changes To help you meet your daily recommended iron ... tofu, dried fruits, and spinach and other dark green leafy vegetables. You can also take an iron ...

  18. The biomedical piglet: establishing reference intervals for haematology and clinical chemistry parameters of two age groups with and without iron supplementation.

    Science.gov (United States)

    Ventrella, Domenico; Dondi, Francesco; Barone, Francesca; Serafini, Federica; Elmi, Alberto; Giunti, Massimo; Romagnoli, Noemi; Forni, Monica; Bacci, Maria L

    2017-01-17

    The similarities between swine and humans in physiological and genomic patterns, and the great correlation in size and anatomy, make pigs extremely useful in preclinical studies. New-born piglets can represent a model for congenital and genetic diseases in new-born children. It is known that piglets may have significant differences in clinicopathological results compared to adult pigs. Therefore, adult laboratory reference intervals cannot be applied to piglets. The aim of this study was to compare haematological and chemical variables in piglets of two ages and determinate age-related reference intervals for commercial hybrid young pigs. Blood samples were collected under general anaesthesia from 130 animals divided into five- (P5) and 30- (P30) day-old piglets. Only P30 animals were treated with parenteral iron after birth. Samples were analysed using automated haematology (ADVIA 2120) and chemistry analysers, and age-related reference intervals were calculated. Significant higher values of RBC, Hb and HCT were observed in P30 animals when compared to P5, with an opposite trend for MCV. These results were associated with a reduction of the RBC regeneration process and the thrombopoietic response. The TSAT and TIBC were significantly higher in P30 compared to P5; however, piglets remained iron deficient compared to adult reference intervals reported previously. In conclusion, this paper emphasises the high variability occurring in clinicopathological variables between new-born and 30-day-old pigs, and between piglets and adult pigs. This study provides valuable reference data for piglets at precise ages and could be used in the future as historical control improving the Reduction in animal experiments, as suggested by the 3Rs principle.

  19. IRON CHELATION THERAPY IN THALASSEMIA SYNDROMES

    Directory of Open Access Journals (Sweden)

    Paolo Cianciulli

    2009-06-01

    Full Text Available Transfusional hemosiderosis is a frequent complication in patients with transfusion dependent chronic diseases such as  thalassemias and severe type of sickle cell diseases. As there are no physiological mechanisms to excrete the iron contained in transfused red cells (1 unit of blood contains approximately 200 mg of iron the excess of iron is stored in various organs. Cardiomyopathy is the most severe complication covering more than 70% of the causes of death of thalassemic patients. Although the current reference standard iron chelator deferoxamine (DFO has been used clinically for over four decades, its effectiveness is limited by a demanding therapeutic regimen that leads to poor compliance. Despite poor compliance, because of the inconvenience of subcutaneous infusion, DFO improved considerably the survival and quality of life of patients with thalassemia. Deferiprone since 1998 and Deferasirox since 2005 were licensed for clinical use. The oral chelators have a better compliance because of oral use, a comparable efficacy to DFO in iron excretion and probably a better penetration to myocardial cells. Considerable increase in iron excretion was documented with combination therapy of DFO and Deferiprone. The proper use of the three chelators will improve the prevention and treatment of iron overload, it will reduce  complications, and improve survival and quality of life of transfused patients

  20. The Study of HFE Genotypes and Its Expression Effect on Iron Status of Iranian Haemochromatosis, Iron Deficiency Anemia Patients, Iron-Taker and Non Iron-Taker Controls.

    Science.gov (United States)

    Beiranvand, Elham; Abediankenari, Saeid; Rostamian, Mosayeb; Beiranvand, Behnoush; Naazeri, Saeed

    2015-01-01

    The role of HFE gene mutations or its expression in regulation of iron metabolism of hereditary haemochromatosis (HH) patients is remained controversial. Therefore here the correlation between two common HFE genotype (p.C282Y, p.H63D) and HFE gene expression with iron status in HH, iron deficiency anemia (IDA) and healthy Iranian participants was studied. For this purpose genotype determination was done by polymerase chain reaction--restriction fragment length polymorphism (PCR-RFLP). Real-Time PCR was applied for evaluation of HFE gene expression. Biochemical parameters and iron consumption were also assessed. Homozygote p.H63D mutation was seen in all HH patients and p.C282Y was not observed in any member of the population. A significant correlation was observed between serum ferritin (SF) level and gender or age of HH patients. p.H63D homozygote was seen to be able to significantly increase SF and transferrin saturation (TS) level without affecting on liver function. Our results also showed that iron consumption affects on TS level increasing. HFE gene expression level of IDA patients was significantly higher than other groups. Also the HFE gene expression was negatively correlated with TS. Finally, the main result of our study showed that loss of HFE function in HH is not derived from its gene expression inhibition and much higher HFE gene expression might lead to IDA. However we propose repeating of the study for more approval of our finding.

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron, in milligrams (mg) at different ages and stages of life. Until the teen years, the recommended amount of ... and choosing iron-rich foods, especially during certain stages of life when more iron is needed, such as childhood ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-fortified breads and cereals, peas, tofu, dried fruits, and dark green leafy vegetables. Foods rich in vitamin C, such as oranges, ... iron-fortified breads and cereals, beans, tofu, dried fruits, and spinach and other dark green leafy vegetables. You can also take an iron supplement. Follow ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... because your body’s intake of iron is too low. Low intake of iron can happen because of blood ... a lot of cow’s milk. Cow’s milk is low in iron. Teens, who have increased need for ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... This is sometimes used to deliver iron through a blood vessel to increase iron levels in the blood. One benefit of IV iron ... over 65 years of age had low hemoglobin levels. This was associated with a greater risk of death even with mild anemia. ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies Women’s ... making new blood cells. Visit our Aplastic Anemia Health Topic to learn more. ... recommend that you take iron supplements, also called iron pills or oral iron, by mouth once or several times a ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... supplements. Iron supplements can change how certain medicines work. Your doctor may suggest check-ups to make sure your ... To prevent complications from iron-deficiency anemia, your doctor may ... during certain stages of life when more iron is needed, such as childhood ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... if you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron-deficiency anemia because of your age, ... or sex. Age You may be at increased risk for iron deficiency at certain ages: Infants between ...

  8. Iron and Immunity

    NARCIS (Netherlands)

    Verbon, E.H.|info:eu-repo/dai/nl/413534049; Trapet, P.L.; Stringlis, I.|info:eu-repo/dai/nl/41185206X; Kruijs, Sophie; Bakker, P.A.H.M.|info:eu-repo/dai/nl/074744623; Pieterse, C.M.J.|info:eu-repo/dai/nl/113115113

    2017-01-01

    Iron is an essential nutrient for most life on Earth because it functions as a crucial redox catalyst in many cellular processes. However, when present in excess iron can lead to the formation of harmful hydroxyl radicals. Hence, the cellular iron balance must be tightly controlled. Perturbation of

  9. Glutathione, Glutaredoxins, and Iron.

    Science.gov (United States)

    Berndt, Carsten; Lillig, Christopher Horst

    2017-11-20

    Glutathione (GSH) is the most abundant cellular low-molecular-weight thiol in the majority of organisms in all kingdoms of life. Therefore, functions of GSH and disturbed regulation of its concentration are associated with numerous physiological and pathological situations. Recent Advances: The function of GSH as redox buffer or antioxidant is increasingly being questioned. New functions, especially functions connected to the cellular iron homeostasis, were elucidated. Via the formation of iron complexes, GSH is an important player in all aspects of iron metabolism: sensing and regulation of iron levels, iron trafficking, and biosynthesis of iron cofactors. The variety of GSH coordinated iron complexes and their functions with a special focus on FeS-glutaredoxins are summarized in this review. Interestingly, GSH analogues that function as major low-molecular-weight thiols in organisms lacking GSH resemble the functions in iron homeostasis. Since these iron-related functions are most likely also connected to thiol redox chemistry, it is difficult to distinguish between mechanisms related to either redox or iron metabolisms. The ability of GSH to coordinate iron in different complexes with or without proteins needs further investigation. The discovery of new Fe-GSH complexes and their physiological functions will significantly advance our understanding of cellular iron homeostasis. Antioxid. Redox Signal. 27, 1235-1251.

  10. Iron Stain on Wood

    Science.gov (United States)

    Mark Knaebe

    2013-01-01

    Iron stain, an unsightly blue–black or gray discoloration, can occur on nearly all woods. Oak, redwood, cypress, and cedar are particularly prone to iron stain because these woods contain large amounts of tannin-like extractives. The discoloration is caused by a chemical reaction between extractives in the wood and iron in steel products, such as nails, screws, and...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... amounts of iron, in milligrams (mg) at different ages and stages of life. Until the teen years, the recommended amount of iron is the same for boys and girls. From birth to 6 months, babies need 0.27 mg of iron. This number goes up to 11 mg for children ages 7 to 12 months, and down to 7 ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... bleeding or other abnormalities, such as growths or cancer of the lining of the colon. For this test, a ... that you take iron supplements, also called iron pills or oral iron, by mouth once or several times a ...

  13. Iron homeostasis during pregnancy.

    Science.gov (United States)

    Fisher, Allison L; Nemeth, Elizabeta

    2017-12-01

    During pregnancy, iron needs to increase substantially to support fetoplacental development and maternal adaptation to pregnancy. To meet these iron requirements, both dietary iron absorption and the mobilization of iron from stores increase, a mechanism that is in large part dependent on the iron-regulatory hormone hepcidin. In healthy human pregnancies, maternal hepcidin concentrations are suppressed in the second and third trimesters, thereby facilitating an increased supply of iron into the circulation. The mechanism of maternal hepcidin suppression in pregnancy is unknown, but hepcidin regulation by the known stimuli (i.e., iron, erythropoietic activity, and inflammation) appears to be preserved during pregnancy. Inappropriately increased maternal hepcidin during pregnancy can compromise the iron availability for placental transfer and impair the efficacy of iron supplementation. The role of fetal hepcidin in the regulation of placental iron transfer still remains to be characterized. This review summarizes the current understanding and addresses the gaps in knowledge about gestational changes in hematologic and iron variables and regulatory aspects of maternal, fetal, and placental iron homeostasis. © 2017 American Society for Nutrition.

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Topics section only, or the News and Resources section. NHLBI Entire Site NHLBI Entire Site Health ... español Iron-deficiency anemia is a common type of anemia that occurs if you do not have enough iron in your body. People with mild or moderate iron-deficiency anemia ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron is too ... clamping of your newborn’s umbilical cord at the time of delivery. This may help prevent iron-deficiency ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... severity of the condition. Your doctor may recommend healthy eating changes, iron supplements, intravenous iron therapy for mild ... you: Adopt healthy lifestyle changes such as heart-healthy eating patterns. Increase your daily intake of iron-rich ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in you getting less than the recommended daily amount of iron. Frequent blood donation. Individuals who donate blood often may be ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Topics News & Resources Intramural Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer ... and symptoms as well as complications from iron-deficiency anemia. Research for Your Health The NHLBI is part of the U.S. Department ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia, your doctor may order the following blood tests to diagnose iron-deficiency anemia: Complete blood count (CBC) to ... than normal when viewed under a microscope. Different tests help your doctor diagnose iron-deficiency anemia. In iron-deficiency anemia, blood ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... for iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ...

  2. Iron and Your Child

    Science.gov (United States)

    ... deficiency isn't corrected, it can lead to iron-deficiency anemia (a decrease in the number of red blood ... Parents Kids Teens Anemia Blood Test: Ferritin (Iron) Iron-Deficiency Anemia Vegetarianism Menstrual Problems Pregnant or Breastfeeding? Nutrients You ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... normally stores but has used up. Increase your intake of vitamin C to help your body absorb iron. Avoid drinking black tea, which reduces iron absorption. Other treatments If you have chronic kidney disease and iron-deficiency anemia, your doctor may recommend ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... different ages and stages of life. Until the teen years, the recommended amount of iron is the ... cow’s milk. Cow’s milk is low in iron. Teens, who have increased need for iron during growth ...

  5. Structure-based discovery of clinically approved drugs as Zika virus NS2B-NS3 protease inhibitors that potently inhibit Zika virus infection in vitro and in vivo.

    Science.gov (United States)

    Yuan, Shuofeng; Chan, Jasper Fuk-Woo; den-Haan, Helena; Chik, Kenn Ka-Heng; Zhang, Anna Jinxia; Chan, Chris Chung-Sing; Poon, Vincent Kwok-Man; Yip, Cyril Chik-Yan; Mak, Winger Wing-Nga; Zhu, Zheng; Zou, Zijiao; Tee, Kah-Meng; Cai, Jian-Piao; Chan, Kwok-Hung; de la Peña, Jorge; Pérez-Sánchez, Horacio; Cerón-Carrasco, José Pedro; Yuen, Kwok-Yung

    2017-09-01

    Zika virus (ZIKV) infection may be associated with severe complications in fetuses and adults, but treatment options are limited. We performed an in silico structure-based screening of a large chemical library to identify potential ZIKV NS2B-NS3 protease inhibitors. Clinically approved drugs belonging to different drug classes were selected among the 100 primary hit compounds with the highest predicted binding affinities to ZIKV NS2B-NS3-protease for validation studies. ZIKV NS2B-NS3 protease inhibitory activity was validated in most of the selected drugs and in vitro anti-ZIKV activity was identified in two of them (novobiocin and lopinavir-ritonavir). Molecular docking and molecular dynamics simulations predicted that novobiocin bound to ZIKV NS2B-NS3-protease with high stability. Dexamethasone-immunosuppressed mice with disseminated ZIKV infection and novobiocin treatment had significantly (P < 0.05) higher survival rate (100% vs 0%), lower mean blood and tissue viral loads, and less severe histopathological changes than untreated controls. This structure-based drug discovery platform should facilitate the identification of additional enzyme inhibitors of ZIKV. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Iron absorption from beans with different contents of iron, evaluated by stable isotopes.

    Science.gov (United States)

    Junqueira-Franco, Márcia Varella Morandi; Dutra de Oliveira, José Eduardo; Nutti, Marilia Regini; Pereira, Helton Santos; Carvalho, José Luiz Vianna de; Abrams, Steven A; Brandão, Camila Fernanda Cunha; Marchini, Júlio Sérgio

    2018-06-01

    of the TBB, probably was not sufficient to improve higher bioavailability. It is recommended to evaluate the not only the absorption of iron in cultivars that present a higher difference in iron concentration but also in association with other components of the Brazilian diet, such as rice and beans. Copyright © 2018 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  7. Intravenous iron treatments for iron deficiency anemia in inflammatory bowel disease: a budget impact analysis of iron isomaltoside 1000 (Monofer) in the UK.

    Science.gov (United States)

    Pollock, R F; Muduma, G

    2017-12-01

    Iron deficiency is the leading cause of anemia in patients with inflammatory bowel disease (IBD). Intravenous iron is the first-line treatment for clinically active IBD or previous oral iron intolerance. The aim of the present study was to develop a comparative model of iron deficiency and delivery for iron isomaltoside (IIM), ferric carboxymaltose (FCM), low molecular weight iron dextran (LMWID), and iron sucrose (IS) in the treatment of iron deficiency anemia associated with IBD. Areas covered: A model was developed to evaluate iron delivery characteristics, resource use and costs associated with IIM, FCM, LMWID and IS. Iron deficiency was modeled using dosing tables and retreatments were modeled based on a pooled retrospective analysis. The analyses were conducted over 5 years in patients with IBD with mean bodyweight of 75.4 kg and hemoglobin levels of 10.77 g/dL based on observational data. Expert opinion: The modeling analysis showed that using IIM required 1.2 infusions (per treatment) to correct the mean iron deficit, compared with 1.6, 1.2, and 7.1 with FCM, LMWID and IS, respectively. Costs were estimated to be 2,518 pounds sterling (GBP) per patient with IIM or LMWID, relative to GBP 3,309 with FCM or GBP 14,382 with IS.

  8. Diurnal variations in iron concentrations and expression of genes involved in iron absorption and metabolism in pigs.

    Science.gov (United States)

    Zhang, Yiming; Wan, Dan; Zhou, Xihong; Long, Ciming; Wu, Xin; Li, Lan; He, Liuqin; Huang, Pan; Chen, Shuai; Tan, Bie; Yin, Yulong

    2017-09-02

    Diurnal variations in serum iron levels have been well documented in clinical studies, and serum iron is an important diagnostic index for iron-deficiency anemia. However, the underlying mechanism of dynamic iron regulation in response to the circadian rhythm is still unclear. In this study, we investigated daily variations in iron status in the plasma and liver of pigs. The transcripts encoding key factors involved in iron uptake and homeostasis were evaluated. The results showed that iron levels in the plasma and liver exhibited diurnal rhythms. Diurnal variations were also observed in transcript levels of divalent metal transporter 1 (DMT1), membrane-associated ferric reductase 1 (DCYTB), and transferrin receptor (TfR) in the duodenum and jejunum, as well as hepcidin (HAMP) and TfR in the liver. Moreover, the results showed a network in which diurnal variations in systemic iron levels were tightly regulated by hepcidin and Tf/TfR via DCYTB and DMT1. These findings provide new insights into circadian iron homeostasis regulation. The diurnal variations in serum iron levels may also have pathophysiological implications for clinical diagnostics related to iron deficiency anemia in pigs. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Laboratory assessment of iron status in pregnancy.

    LENUS (Irish Health Repository)

    Walsh, Thomas

    2012-02-01

    BACKGROUND: Efforts to improve maternal nutrition during pregnancy prompted an observational study of the occurrence of maternal iron deficiency and its laboratory diagnosis in almost 500 pregnancies. METHODS: In this longitudinal study, the biochemical and haematological iron indices of women (n=492) attending a prenatal clinic in a Dublin maternity hospital were assessed at first booking (mean 15.9 weeks), and after 24 weeks, and 36 weeks of gestation. Full blood counts were measured. Serum ferritin (SF), zinc protoporphyrin (ZPP), and transferrin receptor (sTfR) concentrations were assayed and transferrin receptor index (sTfR-Index) was calculated. The occurrence of low values and their diagnostic values were considered. RESULTS: A high occurrence iron deficiency (ID) at first booking (SF<12 mug\\/L) had increased over six-fold by 24 weeks, and all biochemical iron indices reflected progressive iron depletion right up to term. The WHO recommended anaemia "cut-off" (Hb<110 g\\/L) was insensitive to biochemical iron deficiency at booking, missing over 90% of the low SF values (SF<12 mug\\/L) which were mostly associated with much higher Hb levels. CONCLUSIONS: This study stresses the importance of including a biochemical index of iron status in prenatal screening and supports SF as the best indicator of biochemical ID overall. sTfR was insensitive to iron deficiency in early pregnancy, whereas the sTfR-Index, as a ratio, has the potential to distinguish between ID and physiological anaemia, and may offer stability in the assessment of iron stores from early pregnancy to full term. A policy of early screening of both Hb and SF concentrations is recommended as the minimum requirement for surveillance of maternal iron status in pregnancy.

  10. Virtual iron concentration imaging based on dual-energy CT for noninvasive quantification and grading of liver iron content: An iron overload rabbit model study

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Xian Fu; Yang, Yi; Xie, Xue Qian; Zhang, Huan; Chai, Wei Min; Yan, Fu Hua [Shanghai Jiao Tong University School of Medicine, Department of Radiology, Ruijin Hospital, Shanghai (China); Yan, Jing [Siemens Shanghai Medical Equipment Ltd., Shanghai (China); Wang, Li [Fudan University, Center of Analysis and Measurement, Shanghai (China); Schmidt, Bernhard [Siemens AG, Healthcare Sector, Forchheim (Germany)

    2015-09-15

    To assess the accuracy of liver iron content (LIC) quantification and grading ability associated with clinical LIC stratification using virtual iron concentration (VIC) imaging on dual-energy CT (DECT) in an iron overload rabbit model. Fifty-one rabbits were prepared as iron-loaded models by intravenous injection of iron dextran. DECT was performed at 80 and 140 kVp. VIC images were derived from an iron-specific algorithm. Postmortem LIC assessments were conducted on an inductively coupled plasma (ICP) spectrometer. Correlation between VIC and LIC was analyzed. VIC were stratified according to the corresponding clinical LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg Fe/g. Diagnostic performance of stratification was evaluated by receiver operating characteristic analysis. VIC linearly correlated with LIC (r = 0.977, P < 0.01). No significant difference was observed between VIC-derived LICs and ICP (P > 0.05). For the four clinical LIC thresholds, the corresponding cutoff values of VIC were 19.6, 25.3, 36.9, and 61.5 HU, respectively. The highest sensitivity (100 %) and specificity (100 %) were achieved at the threshold of 15.0 mg Fe/g. Virtual iron concentration imaging on DECT showed potential ability to accurately quantify and stratify hepatic iron accumulation in the iron overload rabbit model. (orig.)

  11. Vedolizumab: first global approval.

    Science.gov (United States)

    Poole, Raewyn M

    2014-07-01

    Vedolizumab [Entyvio(®) (US, Europe)], a humanized monoclonal antibody α4β7 integrin receptor antagonist, has been developed by Millennium Pharmaceuticals (d/b/a Takeda Pharmaceuticals International) for the treatment of ulcerative colitis and Crohn's disease. Vedolizumab has received its first global approval for the treatment of ulcerative colitis and Crohn's disease in the US, for use in adult patients with moderate-to-severe disease who have had an inadequate response, loss of response or intolerance to one or more standard therapies (corticosteroids, immunomodulators or tumour necrosis factor-α inhibitor) or demonstrated dependence on corticosteroids. Vedolizumab has since been approved for ulcerative colitis and Crohn's disease in the EU, Norway, Iceland and Liechtenstein. This article summarizes the milestones in the development of vedolizumab leading to its first approval for the treatment of ulcerative colitis and Crohn's disease.

  12. Genetic/metabolic effect of iron metabolism and rare anemias

    Directory of Open Access Journals (Sweden)

    Clara Camaschella

    2013-03-01

    -linked sideroblastic anemia/ataxia, likely impairing the activity of ferrochelatase, which is an iron/sulfur-cluster- dependent enzyme. A recessive form affects GLRX5, a protein involved in the iron/sulfur cluster biogenesis. Aceruloplasminemia is a rare recessive syndrome characterized by anemia, diabetes, retinal degeneration, ataxia and other neurological symptoms, low serum iron but high serum ferritin, due to decreased iron recycling from macrophages and other cells. The study of these rare conditions has greatly contributed to our understanding of iron transport, utilization and recycling. Their distinction is clinically essential in order to plan the best treatment.

  13. Clinical evaluation of neodymium-iron-boron (Ne2Fe14B) rare earth magnets in the treatment of mid line diastemas

    Science.gov (United States)

    Manoj-Kumar, Mitta; Gowri-Sankar, Singaraju; Chaitanya, Nellore; Vivek-Reddy, Ganugapanta; Venkatesh, Nettam

    2016-01-01

    Background To evaluate the closure of midline diastema using the Neodymium-Iron-Boron magnets and to compare the treatment duration of midline diastemas with the use of magnets compared to regular orthodontic treatment. Material and Methods Thirty patients with age group 12 to 30 years with the midline diastema ranging from 0.5 to 3mm were selected. These patients were divided into two groups. Diastema closure in one group was accomplished by conventional method, in other group was done with Ne2Fe14B magnets. These magnets were fitted to the labial surfaces of the maxillary central incisors such a way that the opposite poles of the magnets face each other. At each appointment, study models and radiographs were taken for study subjects and the midline diastema was measured using digital vernier calipers on the study models obtained. Descriptive statistics carried out using Paired t-test. Results Subjects treated with Ne2Fe14B magnets showed a significant difference compared to fixed orthodontic appliance subjects with respect to time of closure, rate of space closure and incisal inclination. Significant difference between 2 groups with reduction of 64.6 days in time to diastema closure in subjects treated with Ne2Fe14B magnets (Pclosure of mid line diastema in less duration of time. Key words:Midline diastema, Ne2Fe14B magnets, rare earth magnets, space closure. PMID:27034757

  14. Project Waiver of American Iron and Steel Requirements to the Napa Sanitation District for 24-Inch Diameter Butterfly Valves

    Science.gov (United States)

    Waiver approval by EPA pursuant to the American Iron and Steel Requirements of the Clean Water Act Section 608 to the Napa Sanitation District in California for the purchase of 24-inch butterfly valves.

  15. CORN, LP Goldfield Approval

    Science.gov (United States)

    This November 19, 2015 letter from EPA approves the petition from CORN, LP, Goldfield facility, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel (D-code 6) RINs under the RFS pro

  16. Poet Fostoria Approval

    Science.gov (United States)

    This August 9, 2016 letter from EPA approves, with modifications, the petition from Poet Biorefining-Fostoria, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel (D-code 6)

  17. Poet Lake Crystal Approval

    Science.gov (United States)

    This September 19, 2016 letter from EPA approves the petition from Poet Biorefining-Lake Crystal, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel (D-code 6) RINs under the RFS

  18. Poet Leipsic Approval

    Science.gov (United States)

    This August 9, 2016 letter from EPA approves,wtih modifications, the petition from Poet Biorefining-Leipsic, LLC, regarding non-grandfathered ethanol produced through a dry mill process, qualifying under the Clean Air Act for renewable fuel (D-code 6) RINs

  19. Drugs Approved for Rhabdomyosarcoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for rhabdomyosarcoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries. There may be drugs used in rhabdomyosarcoma that are not listed here.

  20. An unusual case of iron deficiency anemia is associated with extremely low level of transferrin receptor.

    Science.gov (United States)

    Hao, Shuangying; Li, Huihui; Sun, Xiaoyan; Li, Juan; Li, Kuanyu

    2015-01-01

    A case study of a female patient, diagnosed with iron deficiency anemia, was unresponsive to oral iron treatment and only partially responsive to parenteral iron therapy, a clinical profile resembling the iron-refractory iron deficiency anemia (IRIDA) disorder. However, the patient failed to exhibit microcytic phenotype, one of the IRIDA hallmarks. Biochemical assays revealed that serum iron, hepcidin, interluekin 6, and transferrin saturation were within the normal range of references or were comparable to her non-anemic offspring. Iron contents in serum and red blood cells and hemoglobin levels were measured, which confirmed the partial improvement of anemia after parenteral iron therapy. Strikingly, serum transferrin receptor in patient was almost undetectable, reflecting the very low activity of bone-marrow erythropoiesis. Our data demonstrate that this is not a case of systemic iron deficiency, but rather cellular iron deficit due to the low level of transferrin receptor, particularly in erythroid tissue.

  1. Visualizing Iron Deposition in Multiple Sclerosis Cadaver Brains

    International Nuclear Information System (INIS)

    Habib, Charbel A.; Zheng Weili; Mark Haacke, E.; Webb, Sam; Nichol, Helen

    2010-01-01

    Aim: To visualize and validate iron deposition in two cases of multiple sclerosis using rapid scanning X-Ray Fluorescence (RS-XRF) and Susceptibility Weighted Imaging (SWI). Material and Methods: Two (2) coronal cadaver brain slices from patients clinically diagnosed with multiple sclerosis underwent magnetic resonance imaging (MRI), specifically SWI to image iron content. To confirm the presence of iron deposits and the absence of zinc-rich myelin in lesions, iron and zinc were mapped using RS-XRF. Results: MS lesions were visualized using FLAIR and correlated with the absence of zinc by XRF. XRF and SWI showed that in the first MS case, there were large iron deposits proximal to the draining vein of the caudate nucleus as well as iron deposits associated with blood vessels throughout the globus pallidus. Less iron was seen in association with lesions than in the basal ganglia. The presence of larger amounts of iron correlated reasonably well between RS-XRF and SWI. In the second case, the basal ganglia appeared normal and acute perivascular iron deposition was absent. Conclusion: Perivascular iron deposition is seen in some but not all MS cases, giving credence to the use of SWI to assess iron involvement in MS pathology in vivo.

  2. Mapping and characterization of iron compounds in Alzheimer's tissue

    International Nuclear Information System (INIS)

    Collingwood, Joanna; Dobson, Jon

    2006-01-01

    Understanding the management of iron in the brain is of great importance in the study of neurodegeneration, where regional iron overload is frequently evident. A variety of approaches have been employed, from quantifying iron in various anatomical structures, to identifying genetic risk factors related to iron metabolism, and exploring chelation approaches to tackle iron overload in neurodegenerative disease. However, the ease with which iron can change valence state ensures that it is present in vivo in a wide variety of forms, both soluble and insoluble. Here, we review recent developments in approaches to locate and identify iron compounds in neurodegenerative tissue. In addition to complementary techniques that allow us to quantify and identify iron compounds using magnetometry, extraction, and electron microscopy, we are utilizing a powerful combined mapping/characterization approach with synchrotron X-rays. This has enabled the location and characterization of iron accumulations containing magnetite and ferritin in human Alzheimer's disease (AD) brain tissue sections in situ at micron-resolution. It is hoped that such approaches will contribute to our understanding of the role of unusual iron accumulations in disease pathogenesis, and optimise the potential to use brain iron as a clinical biomarker for early detection and diagnosis.

  3. Iron status determination in pregnancy using the Thomas plot.

    Science.gov (United States)

    Weyers, R; Coetzee, M J; Nel, M

    2016-04-01

    Physiological changes during pregnancy affect routine tests for iron deficiency. The reticulocyte haemoglobin equivalent (RET-He) and serum-soluble transferrin receptor (sTfR) assay are newer diagnostic parameters for the detection of iron deficiency, combined in the Thomas diagnostic plot. We used this plot to determine the iron status of pregnant women presenting for their first visit to an antenatal clinic in Bloemfontein, South Africa. Routine laboratory tests (serum ferritin, full blood count and C-reactive protein) and RET-He and sTfR were performed. The iron status was determined using the Thomas plot. For this study, 103 pregnant women were recruited. According to the Thomas plot, 72.8% of the participants had normal iron stores and erythropoiesis. Iron-deficient erythropoiesis was detected in 12.6%. A third of participants were anaemic. Serum ferritin showed excellent sensitivity but poor specificity for detecting depleted iron stores. HIV status had no influence on the iron status of the participants. Our findings reiterate that causes other than iron deficiency should be considered in anaemic individuals. When compared with the Thomas plot, a low serum ferritin is a sensitive but nonspecific indicator of iron deficiency. The Thomas plot may provide useful information to identify pregnant individuals in whom haematologic parameters indicate limited iron availability for erythropoiesis. © 2015 John Wiley & Sons Ltd.

  4. Cellular iron transport.

    Science.gov (United States)

    Garrick, Michael D; Garrick, Laura M

    2009-05-01

    Iron has a split personality as an essential nutrient that also has the potential to generate reactive oxygen species. We discuss how different cell types within specific tissues manage this schizophrenia. The emphasis in enterocytes is on regulating the body's supply of iron by regulating transport into the blood stream. In developing red blood cells, adaptations in transport manage the body's highest flux of iron. Hepatocytes buffer the body's stock of iron. Macrophage recycle the iron from effete red cells among other iron management tasks. Pneumocytes provide a barrier to prevent illicit entry that, when at risk of breaching, leads to a need to handle the dangers in a fashion essentially shared with macrophage. We also discuss or introduce cell types including renal cells, neurons, other brain cells, and more where our ignorance, currently still vast, needs to be removed by future research.

  5. Daily oral iron supplementation during pregnancy

    Science.gov (United States)

    Peña-Rosas, Juan Pablo; De-Regil, Luz Maria; Dowswell, Therese; Viteri, Fernando E

    2014-01-01

    Background Iron and folic acid supplementation has been the preferred intervention to improve iron stores and prevent anaemia among pregnant women, and it may also improve other maternal and birth outcomes. Objectives To assess the effects of daily oral iron supplements for pregnant women, either alone or in conjunction with folic acid, or with other vitamins and minerals as a public health intervention. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (2 July 2012). We also searched the WHO International Clinical Trials Registry Platform (ICTRP) (2 July 2012) and contacted relevant organisations for the identification of ongoing and unpublished studies. Selection criteria Randomised or quasi-randomised trials evaluating the effects of oral preventive supplementation with daily iron, iron + folic acid or iron + other vitamins and minerals during pregnancy. Data collection and analysis We assessed the methodological quality of trials using standard Cochrane criteria. Two review authors independently assessed trial eligibility, extracted data and conducted checks for accuracy. Main results We included 60 trials. Forty-three trials, involving more than 27,402 women, contributed data and compared the effects of daily oral supplements containing iron versus no iron or placebo. Overall, women taking iron supplements were less likely to have low birthweight newborns (below 2500 g) compared with controls (8.4% versus 10.2%, average risk ratio (RR) 0.81; 95% confidence interval (CI) 0.68 to 0.97, 11 trials, 8480 women) and mean birthweight was 30.81 g greater for those infants whose mothers received iron during pregnancy (average mean difference (MD) 30.81; 95% CI 5.94 to 55.68, 14 trials, 9385 women). Preventive iron supplementation reduced the risk of maternal anaemia at term by 70% (RR 0.30; 95% CI 0.19 to 0.46, 14 trials, 2199 women) and iron deficiency at term by 57% (RR 0.43; 95% CI 0.27 to 0.66, seven trials, 1256 women

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Our ... more information about Donor Iron Deficiency Study - Red Blood Cells ...

  7. Mineralogy and geochemistry of banded iron formation and iron ...

    Indian Academy of Sciences (India)

    The geological complexities of banded iron formation (BIF) and associated iron ores of Jilling–. Langalata iron ore ...... sure to sea water. Uranium in these samples varies ..... Ce oxidation and removal (Elderfield and Greaves. 1982; De Baar et ...

  8. Polypharmacology of Approved Anticancer Drugs.

    Science.gov (United States)

    Amelio, Ivano; Lisitsa, Andrey; Knight, Richard A; Melino, Gerry; Antonov, Alexey V

    2017-01-01

    The major drug discovery efforts in oncology have been concentrated on the development of selective molecules that are supposed to act specifically on one anticancer mechanism by modulating a single or several closely related drug targets. However, a bird's eye view on data from multiple available bioassays implies that most approved anticancer agents do, in fact, target many more proteins with different functions. Here we will review and systematize currently available information on the targets of several anticancer drugs along with revision of their potential mechanisms of action. Polypharmacology of the current antineoplastic agents suggests that drug clinical efficacy in oncology can be achieved only via modulation of multiple cellular mechanisms. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Danish clinical databases: An overview

    DEFF Research Database (Denmark)

    Green, Anders

    2011-01-01

    Clinical databases contain data related to diagnostic procedures, treatments and outcomes. In 2001, a scheme was introduced for the approval, supervision and support to clinical databases in Denmark.......Clinical databases contain data related to diagnostic procedures, treatments and outcomes. In 2001, a scheme was introduced for the approval, supervision and support to clinical databases in Denmark....

  10. Iron Refractory Iron Deficiency Anaemia: A Rare Cause of Iron Deficiency Anaemia

    LENUS (Irish Health Repository)

    McGrath, T

    2018-01-01

    We describe the case of a 17-month-old boy with a hypochromic microcytic anaemia, refractory to oral iron treatment. After exclusion of dietary and gastrointestinal causes of iron deficiency, a genetic cause for iron deficiency was confirmed by finding two mutations in the TMPRSS6 gene, consistent with a diagnosis of iron-refractory iron deficiency anaemia (IRIDA).

  11. Neratinib: First Global Approval.

    Science.gov (United States)

    Deeks, Emma D

    2017-10-01

    Neratinib (Nerlynx™) is an oral, irreversible inhibitor of the human epidermal growth factor receptors HER1 (EGFR), HER2 and HER4. The drug originally arose from research by Wyeth (now Pfizer) and is now being developed by Puma Biotechnology primarily for the treatment of HER2-positive (HER+) breast cancer. Neratinib is approved in the USA for the extended adjuvant treatment of patients with HER2+ early-stage breast cancer who have been previously treated with a trastuzumab-based adjuvant regimen, and is in the preregistration phase for this indication in the EU. Neratinib, as monotherapy and/or combination therapy, is also in phase 3 development for metastatic breast cancer and in phase 1/2 development for advanced breast cancer and other solid tumours, including non-small cell lung cancer, colorectal cancer and glioblastoma. This article summarizes the milestones in the development of neratinib leading to this first approval for breast cancer.

  12. Avelumab: First Global Approval.

    Science.gov (United States)

    Kim, Esther S

    2017-05-01

    Avelumab (Bavencio ® ) is an intravenously administered programmed cell death ligand-1-blocking human antibody initially developed by EMD Serono Inc. (the biopharmaceutical division of Merck KGaA, Darmstadt, Germany) [now jointly developed and commercialized by EMD Serono Inc. and Pfizer] for the treatment of various tumours. It has received accelerated approval in the USA for the treatment of metastatic Merkel cell carcinoma (mMCC) in adults and paediatric patients aged ≥12 years. The marketing authorization application for avelumab in the treatment of mMCC is undergoing regulatory review in the EU, the biologics license application for avelumab in the treatment of urothelial carcinoma is undergoing priority review by the FDA, and avelumab is in various stages of development internationally for a variety of cancers. This article summarizes the milestones in the development of avelumab leading to this first approval for mMCC.

  13. [Insufficient evidence supporting iron supplementation in anaemia during pregnancy].

    Science.gov (United States)

    Wiegerinck, Melanie M; Mol, Ben Willem J

    2012-01-01

    The Royal Dutch Organization of Midwives (KNOV) recently presented their practice guideline 'Anaemia in midwifery practice'. The guideline identified available evidence on diagnosis, prognosis and treatment of anaemia in pregnancy. Anaemia based on iron deficiency and subsequent treatment with iron supplementation are probably the most frequent aspects of care for pregnant women. However, there is surprisingly enough no evidence of the efficacy of iron supplementation treatment on relevant clinical outcomes in pregnant women with anaemia. We plead to make the next guideline a multidisciplinary one. Such a guideline may lead to a large pragmatic trial evaluating the efficacy of iron supplementation treatment for patients with anaemia.

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... exploring about iron-deficiency anemia. Read more New treatments for disorders that lead to iron-deficiency anemia. We are ... and other pathways. This could help develop new therapies for conditions that ... behavior, thinking, and mood during adolescence. Treating anemia in ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... grams per deciliter (g/dl) for men and less than 12 g/dl for women is diagnostic of anemia. In iron-deficiency anemia, ... blood levels of iron will be low, or less than 10 micromoles per liter (mmol/L) for both men and women. Normal levels are 10 to 30 mmol/L. ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... is blood loss during dialysis. People who have chronic kidney disease also often take other medicines—such as proton ... reduces iron absorption. Other treatments If you have chronic kidney disease and iron-deficiency anemia, your doctor may recommend ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... loss and lead to iron-deficiency anemia. Common causes of blood loss that lead to iron-deficiency anemia include: Bleeding in your GI tract, from an ulcer, colon cancer, or regular use of medicines such as aspirin ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... ages and stages of life. Until the teen years, the recommended amount of iron is the same for boys and girls. From birth to 6 months, babies need 0.27 mg of iron. This number goes up to 11 mg for children ages 7 to 12 months, and down to 7 mg for children ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... have less hemoglobin than normal. Hemoglobin is a protein inside red blood cells that carries oxygen from the lungs to tissues ... stored iron has been used. Ferritin is a protein that helps store iron in your ... very young red blood cells. Peripheral smear to see if your red blood ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia. Search the NIH Research Portfolio Online Reporting Tools (RePORT) to learn about research that ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or oral iron, by mouth once or several times a day to increase the iron in your body. This is ... and newer recommendations to increase the length of time between donations to protect blood donors. Cardiovascular Health Study identifies predictors ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or oral iron, by mouth once or several times a day to increase the iron in your body. This is the most common treatment ... and newer recommendations to increase the length of time between donations to protect ... in older adults. The NHLBI-sponsored Cardiovascular Health Study ...

  3. Iron deficiency in children

    African Journals Online (AJOL)

    cell and excess iron is stored as ferritin to protect the cell from oxidative ... iron deficiency has negative effects during pregnancy and in the postpartum period, which affects maternal health ... use of undiluted cow's milk and a predominant cow's milk intake in .... on bone marrow smear or biopsy for the definitive diagnosis of.

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Certain conditions or medicines can decrease your body’s ability to absorb iron and lead to iron-deficiency ... environment or water. Lead interferes with the body’s ability to make hemoglobin. Family history and genetics Von ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. Blood tests to screen for ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Services’ National Institutes of Health (NIH)—the Nation’s biomedical research agency that makes important scientific discoveries to improve ... efforts for iron-deficiency anemia. Learn about exciting research areas that ... This could help develop new therapies for conditions that affect the balance of iron ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Are you curious about how inflammation from chronic diseases can cause iron-deficiency anemia? Read more When there is ... DBDR) is a leader in research on the causes, prevention, and treatment of blood diseases, including iron-deficiency anemia. Search the NIH Research ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how best to treat premature newborns with low hemoglobin levels. We also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... do not have enough iron in your body. People with mild or moderate iron-deficiency anemia may ... as a TMRPSS6 gene mutation that causes a person’s body to make too much of a hormone ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... during the third trimester of pregnancy. Children between ages 1 and 2, especially if they drink a lot of cow’s milk. Cow’s milk is low in iron. Teens, who have increased need for iron during growth spurts. Older adults, especially those ... environments Children who have lead in ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in ... deficiency anemia, your doctor may recommend heart-healthy eating and choosing iron-rich foods, especially during certain stages of life when more ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... stores are developed during the third trimester of pregnancy. Children between ages 1 and 2, especially if they drink a lot of cow’s milk. Cow’s milk is low in iron. Teens, who have increased need for iron during growth ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... other conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ... check the size of your liver and spleen. Blood tests Based on results from blood tests to screen ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... en español Iron-deficiency anemia is a common type of anemia that occurs if you do not ... iron-deficiency anemia and help rule out other types of anemia. Treatment will explain treatment-related complications ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how best to treat premature newborns with low hemoglobin levels. We also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies Women’s Health All Science A- ... to help your body absorb iron. Avoid drinking black tea, which reduces iron ... was associated with a greater risk of death even with mild anemia. Now, anemia in older ...

  17. Iron deficiency in childhood

    NARCIS (Netherlands)

    Uijterschout, L.

    2015-01-01

    Iron deficiency (ID) is the most common micronutrient deficiency in the world. Iron is involved in oxygen transport, energy metabolism, immune response, and plays an important role in brain development. In infancy, ID is associated with adverse effects on cognitive, motor, and behavioral development

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia. Return to Signs, Symptoms, and Complications to review signs and symptoms as well as complications from iron-deficiency ... NIH]) Heavy Menstrual Bleeding (Centers for Disease Control and ... Dietary Supplement Fact Sheet (NIH) Iron-Deficiency Anemia (National Library ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... be at risk for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, ... you are experiencing side effects such as a bad metallic taste, vomiting, diarrhea, constipation, or upset stomach. ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... age, sex, and whether you are pregnant or breastfeeding. Recommended daily iron intake for children and adults. The table lists the recommended amounts of iron, in milligrams (mg) at different ages and stages of life. Until the teen years, the recommended amount of ...

  1. Diagnosis and treatment of iron-deficiency anaemia in pregnancy and postpartum.

    Science.gov (United States)

    Breymann, C; Honegger, C; Hösli, I; Surbek, D

    2017-12-01

    Iron deficiency occurs frequently in pregnancy and can be diagnosed by serum ferritin-level measurement (threshold value iron-deficiency anemia is recommended in every pregnant women, and should be done by serum ferritin-level screening in the first trimester and regular hemoglobin checks at least once per trimester. In the case of iron deficiency with or without anaemia in pregnancy, oral iron therapy should be given as first-line treatment. In the case of severe iron-deficiency anemia, intolerance of oral iron, lack of response to oral iron, or in the case of a clinical need for rapid and efficient treatment of anaemia (e.g., advanced pregnancy), intravenous iron therapy should be administered. In the postpartum period, oral iron therapy should be administered for mild iron-deficiency anemia (haemorrhagic anemia), and intravenous iron therapy for moderately severe-to-severe anemia (Hb iron therapy in pregnancy or postpartum, iron-containing drugs which have been studied in well-controlled clinical trials in pregnancy and postpartum such as ferric carboxymaltose must be preferred for safety reasons. While anaphylactic reactions are extremely are with non-dextrane products, close surveillance during administration is recommended for all intravenous iron products.

  2. Iron replacement therapy

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Coskun, Mehmet; Weiss, Günter

    2016-01-01

    PURPOSE OF REVIEW: Approximately, one-third of the world's population suffers from anemia, and at least half of these cases are because of iron deficiency. With the introduction of new intravenous iron preparations over the last decade, uncertainty has arisen when these compounds should...... be administered and under which circumstances oral therapy is still an appropriate and effective treatment. RECENT FINDINGS: Numerous guidelines are available, but none go into detail about therapeutic start and end points or how iron-deficiency anemia should be best treated depending on the underlying cause...... of iron deficiency or in regard to concomitant underlying or additional diseases. SUMMARY: The study points to major issues to be considered in revisions of future guidelines for the true optimal iron replacement therapy, including how to assess the need for treatment, when to start and when to stop...

  3. Reticulocyte maturity indices in iron deficiency anemia

    Directory of Open Access Journals (Sweden)

    Muriel Wollmann

    2014-01-01

    Full Text Available Objective: The aim of this study was to analyze the reticulocyte maturity indices (low, medium, and high fluorescence ratios in iron deficient 1- to 6-year-old children, and identify the prevalence of iron deficiency anemia in this population. Methods: The present study included 39 subjects, divided into two groups: control subjects (n = 33, and subjects with iron deficiency anemia (n = 6. The results were analyzed by Student's t-test for comparison of means. Differences were considered significant when two-tailed p-value < 0.05. Results: Subjects with iron deficiency anemia presented increases in the proportion of mean (10.3 ± 4.7% vs. 6.0 ± 3.4%; p-value = 0.003, and high fluorescence reticulocytes (2.3 ± 0.87% vs. 0.9 ± 0.9%; p-value = 0.03 compared to the control group. The prevalence of anemia in this population was 15% (n = 6. Conclusion: The indices related to immaturity of reticulocytes are higher in the presence of iron deficiency, thus demonstrating a deficiency in the raw material to form hemoglobin and are, therefore, possible early markers of iron deficiency and anemia. We emphasize the need to standardize these indices for use in clinical practice and lab test results.

  4. Universal iron fortification of foods: the view of a hematologist

    Directory of Open Access Journals (Sweden)

    José Murilo Martins

    2012-01-01

    Full Text Available With the objective of reducing the high incidence of iron deficiency anemia, the Brazilian National Health Surveillance Agency (ANVISA adopted Resolution 344 in December 2002, which made the addition of iron and folic acid to all industrialized wheat and maize flours in Brazil compulsory. After a series of doubts about this universal measure of food fortification, a review of case reports on long-term medicinal iron intake published in the medical literature was undertaken to investigate the clinical behavior of this hematological conduct. Long-term medicinal iron ingestion is an extremely rare and serious situation. The data suggest that there are cases of hemochromatosis in women whose illnesses were accelerated with this therapy. It is very difficult to determine the amount of iron ingested by Brazilian citizens in the current system of fortification, but there is evidence that there has been an appreciable increase. Although iron fortification of food has been recognized by some authors as a good strategy to combat iron deficiency, some nation shave abandoned this measure. The patient with hemochromatosis is the most affected by compulsory iron fortification and as this disease is now considered a public health problem, we believe that Resolution 344 of ANVISA should be reviewed in order to find a solution beneficial to all segments of the Brazilian population; one should not try to correct one condition (iron deficiency by exacerbating another (acceleration of iron overload cases.

  5. A link between premenopausal iron deficiency and breast cancer malignancy

    International Nuclear Information System (INIS)

    Jian, Jinlong; Li, Jinqing; Huang, Xi; Yang, Qing; Shao, Yongzhao; Axelrod, Deborah; Smith, Julia; Singh, Baljit; Krauter, Stephanie; Chiriboga, Luis; Yang, Zhaoxu

    2013-01-01

    Young breast cancer (BC) patients less than 45 years old are at higher risk of dying from the disease when compared to their older counterparts. However, specific risk factors leading to this poorer outcome have not been identified. One candidate is iron deficiency, as this is common in young women and a clinical feature of young age. In the present study, we used immuno-competent and immuno-deficient mouse xenograft models as well as hemoglobin as a marker of iron status in young BC patients to demonstrate whether host iron deficiency plays a pro-metastatic role. We showed that mice fed an iron-deficient diet had significantly higher tumor volumes and lung metastasis compared to those fed normal iron diets. Iron deficiency mainly altered Notch but not TGF-β and Wnt signaling in the primary tumor, leading to the activation of epithelial mesenchymal transition (EMT). This was revealed by increased expression of Snai1 and decreased expression of E-cadherin. Importantly, correcting iron deficiency by iron therapy reduced primary tumor volume, lung metastasis, and reversed EMT markers in mice. Furthermore, we found that mild iron deficiency was significantly associated with lymph node invasion in young BC patients (p<0.002). Together, our finding indicates that host iron deficiency could be a contributor of poor prognosis in young BC patients

  6. The Battle for Iron between Humans and Microbes.

    Science.gov (United States)

    Carver, Peggy L

    2018-01-01

    Iron is an essential micronutrient for bacteria, fungi, and humans; as such, each has evolved specialized iron uptake systems to acquire iron from the extracellular environment. To describe complex 'tug of war' for iron that has evolved between human hosts and pathogenic microorganisms in the battle for this vital nutrient. A review of current literature was performed, to assess current approaches and controversies in iron therapy and chelation in humans. In humans, sequestration (hiding) of iron from invading pathogens is often successful; however, many pathogens have evolved mechanisms to circumvent this approach. Clinically, controversy continues whether iron overload or administration of iron results in an increased risk of infection. The administration of iron chelating agents and siderophore- conjugate drugs to infected hosts seems a biologically plausible approach as adjunctive therapy in the treatment of infections caused by pathogens dependent on host iron supply (e.g. tuberculosis, malaria, and many bacterial and fungal pathogens); however, thus far, studies in humans have proved unsuccessful. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Iron Deficiency Anemia: A Common and Curable Disease

    Science.gov (United States)

    Miller, Jeffery L.

    2013-01-01

    Iron deficiency anemia arises when the balance of iron intake, iron stores, and the body's loss of iron are insufficient to fully support production of erythrocytes. Iron deficiency anemia rarely causes death, but the impact on human health is significant. In the developed world, this disease is easily identified and treated, but frequently overlooked by physicians. In contrast, it is a health problem that affects major portions of the population in underdeveloped countries. Overall, the prevention and successful treatment for iron deficiency anemia remains woefully insufficient worldwide, especially among underprivileged women and children. Here, clinical and laboratory features of the disease are discussed, and then focus is placed on relevant economic, environmental, infectious, and genetic factors that converge among global populations. PMID:23613366

  8. Comparative evaluation of nephrotoxicity and management by macrophages of intravenous pharmaceutical iron formulations.

    Directory of Open Access Journals (Sweden)

    James R Connor

    Full Text Available There is a significant clinical need for effective treatment of iron deficiency. A number of compounds that can be administered intravenously have been developed. This study examines how the compounds are handled by macrophages and their relative potential to provoke oxidative stress.Human kidney (HK-2 cells, rat peritoneal macrophages and renal cortical homogenates were exposed to pharmaceutical iron preparations. Analyses were performed for indices of oxidative stress and cell integrity. In addition, in macrophages, iron uptake and release and cytokine secretion was monitored.HK-2 cell viability was decreased by iron isomaltoside and ferumoxytol and all compounds induced lipid peroxidation. In the renal cortical homogenates, lipid peroxidation occurred at lowest concentrations with ferric carboxymaltose, iron dextran, iron sucrose and sodium ferric gluconate. In the macrophages, iron sucrose caused loss of cell viability. Iron uptake was highest for ferumoxytol and iron isomaltoside and lowest for iron sucrose and sodium ferric gluconate. Iron was released as secretion of ferritin or as ferrous iron via ferroportin. The latter was blocked by hepcidin. Exposure to ferric carboxymaltose and iron dextran resulted in release of tumor necrosis factor α.Exposure to iron compounds increased cell stress but was tissue and dose dependent. There was a clear difference in the handling of iron from the different compounds by macrophages that suggests in vivo responses may differ.

  9. Role of glutaredoxin 3 in iron homeostasis

    Science.gov (United States)

    Iron is an essential mineral nutrient that is tightly regulated through mechanisms involving iron regulatory genes, intracellular storage, and iron recycling. Dysregulation of these mechanisms often results in either excess tissue iron accumulation (overload) or iron deficiency (anemia). Many bioche...

  10. The effect of cryoprotection on the use of PLGA encapsulated iron oxide nanoparticles for magnetic cell labeling

    International Nuclear Information System (INIS)

    Tang, Kevin S; Shapiro, Erik M; Hashmi, Sarah M

    2013-01-01

    Magnetic PLGA nanoparticles are a significant advancement in the quest to translate MRI-based cell tracking to the clinic. The benefits of these types of particles are that they encapsulate large amounts of iron oxide nanocrystals within an FDA-approved polymer matrix, combining the best aspects of inert micron-sized iron oxide particles, or MPIOs, and biodegradable small particles of iron oxide, or SPIOs. Practically, PLGA nanoparticle fabrication and storage requires some form of cryoprotectant to both protect the particle during freeze drying and to promote resuspension. While this is a commonly employed procedure in the fabrication of drug loaded PLGA nanoparticles, it has yet to be investigated for magnetic particles and what effect this might have on internalization of magnetic particles. As such, in this study, magnetic PLGA nanoparticles were fabricated with various concentrations of two common cryoprotectants, dextrose and sucrose, and analyzed for their ability to magnetically label cells. It was found that cryoprotection with either sugar significantly enhanced the ability to resuspend nanoparticles without aggregation. Magnetic cell labeling was impacted by sugar concentration, with higher sugar concentrations used during freeze drying more significantly reducing magnetic cell labeling than lower concentrations. These studies suggest that cryoprotection with 1% dextrose is an optimal compromise that preserves monodispersity following resuspension and high magnetic cell labeling. (paper)

  11. Lymph node metastases from head and neck squamous cell carcinoma: MR imaging with ultrasmall superparamagnetic iron oxide particles (Sinerem MR) - results of a phase-III multicenter clinical trial

    International Nuclear Information System (INIS)

    Sigal, R.; Viala, J.; Bosq, J.; Vogl, T.; Mack, M.; Casselman, J.; Depondt, M.; Mattelaer, C.; Moulin, G.; Petit, P.; Champsaur, P.; Veillon, F.; Riehm, S.; Dadashitazehozi, Y.; Hermans, R.; de Jaegere, T.; Marchal, G.; Dubrulle, F.; Chevalier, D.; Lemaitre, L.; Kubiak, C.; Helmberger, R.; Halimi, P.

    2002-01-01

    The aim of this study was to compare the clinical usefulness of ultrasmall superparamagnetic iron oxide (USPIO) MR contrast media (Sinerem, Guerbet Laboratories, Aulnay-sous-Bois, France) with precontrast MRI in the diagnosis of metastatic lymph nodes in patients with head and neck squamous cell carcinoma, using histology as gold standard. Eighty-one previously untreated patients were enrolled in a multicenter phase-III clinical trial. All patients had a noncontrast MR, a Sinerem MR, and surgery within a period of 15 days. The MR exams were analyzed both on site and by two independent radiologists (centralized readers). Correlation between histology and imaging was done per lymph node groups, and per individual lymph nodes when the short axis was ≥10 mm. For individual lymph nodes, Sinerem MR showed a high sensitivity (≥88%) and specificity (≥77%). For lymph node groups, the sensitivity was ≥59% and specificity ≥81%. False-positive results were partially due to inflammatory nodes; false-negative results from the presence of undetected micrometastases. Errors of interpretation were also related to motion and/or susceptibility artifacts and problems of zone assignment. Sinerem MR had a negative predictive value (NPV) ≥90% and a positive predictive value (PPV) ≥51%. The specificity and PPV of Sinerem MR were better than those of precontrast MR. Precontrast MR showed an unexpectedly high sensitivity and NPV which were not increased with Sinerem MR. The potential contribution of Sinerem MR still remains limited by technical problems regarding motion and susceptibility artifacts and spatial resolution. It is also noteworthy that logistical problems, which could reduce the practical value of Sinerem MR, will be minimized in the future since Sinerem MR alone performed as good as the combination of precontrast and Sinerem MR. (orig.)

  12. Lymph node metastases from head and neck squamous cell carcinoma: MR imaging with ultrasmall superparamagnetic iron oxide particles (Sinerem MR) - results of a phase-III multicenter clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Sigal, R.; Viala, J.; Bosq, J. [Department of Radiology, Institut Gustave Roussy, Villejuif (France); Vogl, T.; Mack, M. [Institut fuer Diagnostische und Interventionelle Radiologie, Universitaetsklinikum, Frankfurt Main (Germany); Casselman, J.; Depondt, M.; Mattelaer, C. [Department of Radiology, Brugge (Belgium); Moulin, G.; Petit, P.; Champsaur, P. [Hopital de la Timone, Marseille (France); Veillon, F.; Riehm, S.; Dadashitazehozi, Y. [Hopital de Hautepierre, Avenue Moliere, 67098 Strasbourg (France); Hermans, R.; de Jaegere, T.; Marchal, G. [Department of Radiology, University Hospitals Gasthuisberg, KU Leuven, Heerestraat 49, 3000 Leuven (Belgium); Dubrulle, F.; Chevalier, D.; Lemaitre, L. [Hopital Huriez, 1 place Verdun, 59037 Lille (France); Kubiak, C.; Helmberger, R.; Halimi, P.

    2002-05-01

    The aim of this study was to compare the clinical usefulness of ultrasmall superparamagnetic iron oxide (USPIO) MR contrast media (Sinerem, Guerbet Laboratories, Aulnay-sous-Bois, France) with precontrast MRI in the diagnosis of metastatic lymph nodes in patients with head and neck squamous cell carcinoma, using histology as gold standard. Eighty-one previously untreated patients were enrolled in a multicenter phase-III clinical trial. All patients had a noncontrast MR, a Sinerem MR, and surgery within a period of 15 days. The MR exams were analyzed both on site and by two independent radiologists (centralized readers). Correlation between histology and imaging was done per lymph node groups, and per individual lymph nodes when the short axis was {>=}10 mm. For individual lymph nodes, Sinerem MR showed a high sensitivity ({>=}88%) and specificity ({>=}77%). For lymph node groups, the sensitivity was {>=}59% and specificity {>=}81%. False-positive results were partially due to inflammatory nodes; false-negative results from the presence of undetected micrometastases. Errors of interpretation were also related to motion and/or susceptibility artifacts and problems of zone assignment. Sinerem MR had a negative predictive value (NPV) {>=}90% and a positive predictive value (PPV) {>=}51%. The specificity and PPV of Sinerem MR were better than those of precontrast MR. Precontrast MR showed an unexpectedly high sensitivity and NPV which were not increased with Sinerem MR. The potential contribution of Sinerem MR still remains limited by technical problems regarding motion and susceptibility artifacts and spatial resolution. It is also noteworthy that logistical problems, which could reduce the practical value of Sinerem MR, will be minimized in the future since Sinerem MR alone performed as good as the combination of precontrast and Sinerem MR. (orig.)

  13. Material specification for ductile cast iron in the United States

    International Nuclear Information System (INIS)

    Sorenson, K.B.

    1987-01-01

    The United States currently does not have formal design criteria for qualifying ductile cast iron (DCI) transportation casks. There is also no dedicated material standard for DCI for this particular application. A draft ASTM material specification has been written and is currently in the ASTM approval process. This paper reviews the brief history of the development of the specification, the technical basis for the material properties, the ASTM approval process and the current status of the draft specification. The expected implications of having an adopted ASTM specification on the licensing process are also discussed. (orig./DG)

  14. Myelodysplastic syndromes and the role of iron overload.

    Science.gov (United States)

    Harvey, R Donald

    2010-04-01

    The epidemiology of myelodysplastic syndromes (MDS) and iron overload, recent clinical findings that highlight the importance of actively managing iron overload, and recommendations for initiating and maintaining iron chelation therapy (ICT) are summarized. MDS are a variety of hematological disorders with differing time courses. Disease morbidities are primarily due to cytopenias and evolution to acute myeloid leukemia. Iron overload is a serious complication in patients with MDS due to the long-term use of red blood cell transfusions in patients with symptomatic anemia. Clinical consequences of iron overload include end-organ damage and dysfunction, an increased frequency of transplant-related complications, and reduced survival rates. To prevent these complications, recommendations for initiating and maintaining ICT should be followed by clinicians caring for patients with MDS and iron overload. As current therapeutic options for patients with MDS do not always reduce the transfusion burden, many patients will still need long-term transfusion therapy. Strategies for the management of iron overload in MDS should be considered early in the disease course and in appropriate patients in order to prevent negative clinical outcomes associated with excessive iron accumulation.

  15. Supercollider: Footprint approved

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    With the 'footprint' - the precise location of the 87-kilometre US Superconducting Supercollider, SSC, and its ancillary buildings - now approved, teams of specialists commissioned by the State of Texas swing into action to procure the 17,000 acres (69 million square metres) of land covered by the project. With the SSC Laboratory in Ellis County and the US Department of Energy (DoE, the overseeing government agency) both hiring manpower for this project to collide 20 TeV (20,000 GeV) proton beams before the end of the century, the host State of Texas is providing a helping hand

  16. Management of Iron-Deficiency Anemia in Inflammatory Bowel Disease

    Science.gov (United States)

    Nielsen, Ole Haagen; Ainsworth, Mark; Coskun, Mehmet; Weiss, Günter

    2015-01-01

    Abstract Anemia is the most frequent complication of inflammatory bowel disease (IBD), but anemia, mostly due to iron deficiency, has long been neglected in these patients. The aim was to briefly present the pathophysiology, followed by a balanced overview of the different forms of iron replacement available, and subsequently, to perform a systematic review of studies performed in the last decade on the treatment of iron-deficiency anemia in IBD. Given that intravenous therapies have been introduced in the last decade, a systematic review performed in PubMed, EMBASE, the Cochrane Library, and the websites of WHO, FDA, and EMA covered prospective trials investigating the management of iron-deficiency anemia in IBD published since 2004. A total of 632 articles were reviewed, and 13 articles (2906 patients) with unique content were included. In general, oral supplementation in iron-deficiency anemia should be administered with a target to restore/replenish the iron stores and the hemoglobin level in a suitable way. However, in patients with IBD flares and inadequate responses to or side effects with oral preparations, intravenous iron supplementation is the therapy of choice. Neither oral nor intravenous therapy seems to exacerbate the clinical course of IBD, and intravenous iron therapy can be administered even in active disease stages and concomitantly with biologics. In conclusion, because many physicians are in doubt as to how to manage anemia and iron deficiency in IBD, there is a clear need for the implementation of evidence-based recommendations on this matter. Based on the data presented, oral iron therapy should be preferred for patients with quiescent disease stages and trivial iron deficiency anemia unless such patients are intolerant or have an inadequate response, whereas intravenous iron supplementation may be of advantage in patients with aggravated anemia or flares of IBD because inflammation hampers intestinal absorption of iron. PMID:26061331

  17. Liver Iron Contents in Rats after Administration of Certain Iron ...

    African Journals Online (AJOL)

    The effect of consumption of certain iron compounds on liver iron deposition was ... extra iron probably depends on the type of food prepared, .... main groups. Each main group consisted of 4 subgroups. (8 rats per subgroup) which received the same basic diet but differing amounts of iron of a specific type. Each animal was ...

  18. Complexity of intravenous iron nanoparticle formulations: implications for bioequivalence evaluation.

    Science.gov (United States)

    Pai, Amy Barton

    2017-11-01

    Intravenous iron formulations are a class of complex drugs that are commonly used to treat a wide variety of disease states associated with iron deficiency and anemia. Venofer® (iron-sucrose) is one of the most frequently used formulations, with more than 90% of dialysis patients in the United States receiving this formulation. Emerging data from global markets outside the United States, where many iron-sucrose similars or copies are available, have shown that these formulations may have safety and efficacy profiles that differ from the reference listed drug. This may be attributable to uncharacterized differences in physicochemical characteristics and/or differences in labile iron release. As bioequivalence evaluation guidance evolves, clinicians should be educated on these potential clinical issues before a switch to the generic formulation is made in the clinical setting. © 2017 New York Academy of Sciences.

  19. Iatrogenic Iron Overload in Dialysis Patients at the Beginning of the 21st Century.

    Science.gov (United States)

    Rostoker, Guy; Vaziri, Nosratola D; Fishbane, Steven

    2016-05-01

    Iron overload used to be considered rare in hemodialysis patients but its clinical frequency is now increasingly realized. The liver is the main site of iron storage and the liver iron concentration (LIC) is closely correlated with total iron stores in patients with secondary hemosideroses and genetic hemochromatosis. Magnetic resonance imaging is now the gold standard method for LIC estimation and monitoring in non-renal patients. Studies of LIC in hemodialysis patients by quantitative magnetic resonance imaging and magnetic susceptometry have demonstrated a strong relation between the risk of iron overload and the use of intravenous (IV) iron products prescribed at doses determined by the iron biomarker cutoffs contained in current anemia management guidelines. These findings have challenged the validity of both iron biomarker cutoffs and current clinical guidelines, especially with respect to recommended IV iron doses. Three long-term observational studies have recently suggested that excessive IV iron doses may be associated with an increased risk of cardiovascular events and death in hemodialysis patients. We postulate that iatrogenic iron overload in the era of erythropoiesis-stimulating agents may silently increase complications in dialysis patients without creating frank clinical signs and symptoms. High hepcidin-25 levels were recently linked to fatal and nonfatal cardiovascular events in dialysis patients. It is therefore tempting to postulate that the main pathophysiological pathway leading to these events may involve the pleiotropic master hormone hepcidin (synergized by fibroblast growth factor 23), which regulates iron metabolism. Oxidative stress as a result of IV iron infusions and iron overload, by releasing labile non-transferrin-bound iron, might represent a 'second hit' on the vascular bed. Finally, iron deposition in the myocardium of patients with severe iron overload might also play a role in the pathogenesis of sudden death in some patients.

  20. FERRIC CITRATE: AN IRON-BASED ORAL PHOSPHATE BINDER

    Directory of Open Access Journals (Sweden)

    T. Christopher Bond

    2012-06-01

    Based on actual physician behavior in response to ferritin and TSAT increases and ferric citrate clinical trial results, and assuming equivalent pricing to other PBs, there would be cost savings with ferric citrate use through reduced ESA and iron use.

  1. [Ferrous sulfate in the treatment of iron deficiency anemia: The positions continue].

    Science.gov (United States)

    Dvoretsky, L I

    The paper discusses treatment strategy and tactics for iron deficiency anemia. It gives data on the comparative efficacy of different iron sulfate drugs, their bioavailability, effects on peroxidation processes, and side effects. The paper also considers the clinical significance of a dosage form of iron-containing drugs with a sustained iron release, as well as ways to reduce the frequency and magnitude of side effects when ferrous sulfate is used.

  2. Medication adherence to oral iron therapy in patients with iron deficiency anemia

    Science.gov (United States)

    Gereklioglu, Cigdem; Asma, Suheyl; Korur, Asli; Erdogan, Ferit; Kut, Altug

    2016-01-01

    Objective: This study aimed at investigating the factors affecting medication adherence in patients who use oral iron therapy due to iron deficiency anemia. Methods: A total of 96 female patients in fertile age with mean age of 30±10.1 years (range 18-53) who were admitted to Family Medicine Clinic between 01 January and 31 March 2015 and who had received iron therapy within the recent three years were enrolled in the study. Data were collected through a questionnaire form. Results: Of the patients, 39 (40,6%) were detected not to use the medication regularly or during the recommended period. A statistically significant relationship was found between non-adherence to therapy and gastrointestinal side effects and weight gain (p<0.05). Conclusion: Medication adherence is deficient in patients with iron deficiency anemia. The most important reason for this seems gastrointestinal side effects, in addition to weight gain under treatment. PMID:27375698

  3. Medication adherence to oral iron therapy in patients with iron deficiency anemia.

    Science.gov (United States)

    Gereklioglu, Cigdem; Asma, Suheyl; Korur, Asli; Erdogan, Ferit; Kut, Altug

    2016-01-01

    This study aimed at investigating the factors affecting medication adherence in patients who use oral iron therapy due to iron deficiency anemia. A total of 96 female patients in fertile age with mean age of 30±10.1 years (range 18-53) who were admitted to Family Medicine Clinic between 01 January and 31 March 2015 and who had received iron therapy within the recent three years were enrolled in the study. Data were collected through a questionnaire form. Of the patients, 39 (40,6%) were detected not to use the medication regularly or during the recommended period. A statistically significant relationship was found between non-adherence to therapy and gastrointestinal side effects and weight gain (p<0.05). Medication adherence is deficient in patients with iron deficiency anemia. The most important reason for this seems gastrointestinal side effects, in addition to weight gain under treatment.

  4. Oral iron supplements for children in malaria-endemic areas

    Science.gov (United States)

    Neuberger, Ami; Okebe, Joseph; Yahav, Dafna; Paul, Mical

    2016-01-01

    Background Iron-deficiency anaemia is common during childhood. Iron administration has been claimed to increase the risk of malaria. Objectives To evaluate the effects and safety of iron supplementation, with or without folic acid, in children living in areas with hyperendemic or holoendemic malaria transmission. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library, MEDLINE (up to August 2015) and LILACS (up to February 2015). We also checked the metaRegister of Controlled Trials (mRCT) and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to February 2015. We contacted the primary investigators of all included trials, ongoing trials, and those awaiting assessment to ask for unpublished data and further trials. We scanned references of included trials, pertinent reviews, and previous meta-analyses for additional references. Selection criteria We included individually randomized controlled trials (RCTs) and cluster RCTs conducted in hyperendemic and holoendemic malaria regions or that reported on any malaria-related outcomes that included children younger than 18 years of age. We included trials that compared orally administered iron, iron with folic acid, and iron with antimalarial treatment versus placebo or no treatment. We included trials of iron supplementation or fortification interventions if they provided at least 80% of the Recommended Dietary Allowance (RDA) for prevention of anaemia by age. Antihelminthics could be administered to either group, and micronutrients had to be administered equally to both groups. Data collection and analysis The primary outcomes were clinical malaria, severe malaria, and death from any cause. We assessed the risk of bias in included trials with domain-based evaluation and assessed the quality of the evidence using the Grading of Recommendations Assessment

  5. Screening for iron deficiency and iron deficiency anaemia in pregnancy: a structured review and gap analysis against UK national screening criteria.

    Science.gov (United States)

    Rukuni, Ruramayi; Knight, Marian; Murphy, Michael F; Roberts, David; Stanworth, Simon J

    2015-10-20

    Iron deficiency anaemia is a common problem in pregnancy despite national recommendations and guidelines for treatment. The aim of this study was to appraise the evidence against the UK National Screening Committee (UKNSC) criteria as to whether a national screening programme could reduce the prevalence of iron deficiency anaemia and/or iron deficiency in pregnancy and improve maternal and fetal outcomes. Search strategies were developed for the Cochrane library, Medline and Embase to identify evidence relevant to UK National Screening Committee (UKNSC) appraisal criteria which cover the natural history of iron deficiency and iron deficiency anaemia, the tests for screening, clinical management and evidence of cost effectiveness. Many studies evaluated haematological outcomes of anaemia, but few analysed clinical consequences. Haemoglobin and ferritin appeared the most suitable screening tests, although future options may follow recent advances in understanding iron homeostasis. The clinical consequences of iron deficiency without anaemia are unknown. Oral and intravenous iron are effective in improving haemoglobin and iron parameters. There have been no trials or economic evaluations of a national screening programme for iron deficiency anaemia in pregnancy. Iron deficiency in pregnancy remains an important problem although effective tests and treatment exist. A national screening programme could be of value for early detection and intervention. However, high quality studies are required to confirm whether this would reduce maternal and infant morbidity and be cost effective.

  6. Iron overload patients with unknown etiology from national survey in Japan.

    Science.gov (United States)

    Ikuta, Katsuya; Hatayama, Mayumi; Addo, Lynda; Toki, Yasumichi; Sasaki, Katsunori; Tatsumi, Yasuaki; Hattori, Ai; Kato, Ayako; Kato, Koichi; Hayashi, Hisao; Suzuki, Takahiro; Kobune, Masayoshi; Tsutsui, Miyuki; Gotoh, Akihiko; Aota, Yasuo; Matsuura, Motoo; Hamada, Yuzuru; Tokuda, Takahiro; Komatsu, Norio; Kohgo, Yutaka

    2017-03-01

    Transfusion is believed to be the main cause of iron overload in Japan. A nationwide survey on post-transfusional iron overload subsequently led to the establishment of guidelines for iron chelation therapy in this country. To date, however, detailed clinical information on the entire iron overload population in Japan has not been fully investigated. In the present study, we obtained and studied detailed clinical information on the iron overload patient population in Japan. Of 1109 iron overload cases, 93.1% were considered to have occurred post-transfusion. There were, however, 76 cases of iron overload of unknown origin, which suggest that many clinicians in Japan may encounter some difficulty in correctly diagnosing and treating iron overload. Further clinical data were obtained for 32 cases of iron overload of unknown origin; median of serum ferritin was 1860.5 ng/mL. As occurs in post-transfusional iron overload, liver dysfunction was found to be as high as 95.7% when serum ferritin levels exceeded 1000 ng/mL in these patients. Gene mutation analysis of the iron metabolism-related genes in 27 cases of iron overload with unknown etiology revealed mutations in the gene coding hemojuvelin, transferrin receptor 2, and ferroportin; this indicates that although rare, hereditary hemochromatosis does occur in Japan.

  7. Roles of iron in the survival, growth, and pathogenesis of Legionella pneumophila

    International Nuclear Information System (INIS)

    Quinn, F.D.

    1985-01-01

    The essentially of iron for living cells has long been recognized, and the availability of host-iron has been proposed as a contributing factor to virulence in bacterial, fungal, and protozoan infections. The mechanism by which legionella pneumophila causes disease is unknown. Growth of fresh clinical or environmental isolates in pure culture requires 20 times more iron than is needed for most other bacteria. Thus, increased plasma iron levels may be needed for multiplication within human hosts. It was observed that: (1) this organism can be more readily deprived of iron by iron binding agents than all other bacteria studied, and this inhibition can be reversed by the addition of iron; (2) normal human blood serum kills L. pneumophila and the bactericidal action is decreased when complement is inactivated or enough iron to saturate serum transferrin is added to the system; (3) in assays with a radioactive isotope of iron ( 55 Fe), no specific iron sequestering system was detected; (4) in analysis of outer membrane proteins with 55 Fe, SDS-polyacrylamide gel electrophoresis, and autoradiography, no specific outer membrane proteins responsible for iron acquisition were observed; and (5) in assays for protease, iron does not stimulate production of extracellular proteases. These observations indicate that L. pneumophila has no specific iron uptake mechanism, but instead relies on passive diffusion and/or non-specific mechanisms to obtain its iron

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... for gastrointestinal bleeding To see if gastrointestinal bleeding is causing your iron-deficiency anemia, your doctor may order the following procedures to guide treatment . Fecal ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and dark green leafy vegetables. Foods rich in vitamin C, such as oranges, strawberries, and tomatoes, may help ... but has used up. Increase your intake of vitamin C to help your body absorb iron. Avoid drinking ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Supplement Fact Sheet (NIH) Iron-Deficiency Anemia (National Library of Medicine, MedlinePlus) ... Privacy Policy Freedom of Information Act (FOIA) Accessibility Copyright and Usage No FEAR ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... which causes bleeding in the bowels Frequent blood donation Frequent blood tests, especially in infants and small ... the recommended daily amount of iron. Frequent blood donation. Individuals who donate blood often may be at ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and Strategic Vision Leadership Scientific Divisions Operations and Administration Advisory Committees Budget and Legislative Information Jobs and ... may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough ... these usually go away within a day or two. Red blood cell transfusions. These may be used ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... more. Read less Reminders Return to Causes to review how blood loss, not consuming the recommended amount ... iron-deficiency anemia. Return to Risk Factors to review family history, lifestyle, unhealthy environments, or other factors ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... detect signs of iron-deficiency anemia and help rule out other types of anemia. Treatment will explain ... your blood. More testing may be needed to rule out other types of anemia. Tests for gastrointestinal ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Health [NIH]) Heavy Menstrual Bleeding (Centers for Disease Control and Prevention) Iron - Health Professional Fact ... Email Alerts Receive automatic alerts about NHLBI related news and highlights from ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... may be at an even higher risk, as most of a newborn’s iron stores are developed during ... concentrating Dizziness Fatigue, or feeling tired, is the most common symptom. This can make it hard to ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and cereals, peas, tofu, dried fruits, and dark green leafy vegetables. Foods rich in vitamin C, such ... tofu, dried fruits, and spinach and other dark green leafy vegetables. You can also take an iron ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... age, sex, and whether you are pregnant or breastfeeding. Recommended daily iron intake for children and adults. ... need 8 mg. Pregnant women need 27 mg. Breastfeeding girls under age 18 need 10 mg while ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... order blood tests or other diagnostic tests. Physical exam Your doctor may ask about your medical history ... has used up. Increase your intake of vitamin C to help your body absorb iron. Avoid drinking ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... person’s body to make too much of a hormone called hepcidin. Hepcidin blocks the intestine from taking ... is inflammation, your liver makes more of a hormone called hepcidin. Hepcidin prevents iron from leaving cells ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... improve health through research and scientific discovery. Improving health with current research Learn about the following ways ... from needing iron supplementation. Advancing research for improved health In support of our mission , we are committed ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... research and scientific discovery. Improving health with current research Learn about the following ways that NHLBI continues ... and protect individuals from needing iron supplementation. Advancing research for improved health In support of our mission , ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Are you a frequent blood donor living in New York City? This study is looking at how iron- ... donate blood frequently. This study is located in New York City, and is recruiting by invitation only. View ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this Health ... lead to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Blood Disorders and Blood Safety Sleep Science and Sleep Disorders Lung Diseases Heart and Vascular Diseases Precision Medicine ... prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the current ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Frequent blood donation Frequent blood tests, especially in infants and small children Heavy menstrual periods Injury or ... boys and girls. From birth to 6 months, babies need 0.27 mg of iron. This number ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... is caused by strong muscle contractions and the impact of feet repeatedly striking the ground, such as ... funding on iron-deficiency anemia. We stimulate high-impact research. Our Trans-Omics for Precision Medicine (TOPMed) ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... common type of anemia that occurs if you do not have enough iron in your body. People ... make it hard to find the energy to do normal activities. Headache Irregular heartbeat. This is a ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Iron-Deficiency Anemia (National Library of Medicine, MedlinePlus) Building 31 31 Center Drive Bethesda, MD 20892 Learn ... and Usage No FEAR Act Grants and Funding Building 31 31 Center Drive Bethesda, MD 20892 Learn ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... may recommend erythropoiesis stimulating agents (esa) . These medicines stimulate the bone marrow to make more red blood ... NHLBI is funding on iron-deficiency anemia. We stimulate high-impact research. Our Trans-Omics for Precision ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... lifestyle changes to avoid complications. Follow your treatment plan Do not stop taking your prescribed iron supplements ... warning signs of serious complications and have a plan Tell your doctor if you have any new ...

  13. Banded Iron Formations

    DEFF Research Database (Denmark)

    Posth, Nicole R; Konhauser, Kurt O; Kappler, Andreas

    2011-01-01

    Sedimentary deposits of alternating iron-rich (20–40% Fe) and iron-poor, siliceous (40–50% SiO2) mineral layers that primarily precipitated throughout much of the late Archean (2.7–2.5 Ga) and Paleoproterozoic (2.5– 1.8 Ga), but then remerged in the Neoproterozoic (0.8 Ga).......Sedimentary deposits of alternating iron-rich (20–40% Fe) and iron-poor, siliceous (40–50% SiO2) mineral layers that primarily precipitated throughout much of the late Archean (2.7–2.5 Ga) and Paleoproterozoic (2.5– 1.8 Ga), but then remerged in the Neoproterozoic (0.8 Ga)....

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this Health ... to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. People ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... view the colon directly. What if my doctor thinks something else is causing my iron-deficiency anemia? ... deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... tests, especially in infants and small children Heavy menstrual periods Injury or surgery Urinary tract bleeding Consuming ... iron-deficiency anemia from trauma, surgery, or heavy menstrual periods. Individuals with a gene for hemophilia, including ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and naproxen Certain rare genetic conditions such as hereditary hemorrhagic telangiectasia, which causes bleeding in the bowels ... iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... lead in their blood from their environment or water. Lead interferes with the body’s ability to make ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies Women’s Health All Science A- ... Teens, who have increased need for iron during growth spurts. Older adults, especially those over age 65. ...

  20. Ocean iron fertilization

    Digital Repository Service at National Institute of Oceanography (India)

    Naqvi, S.W.A.; Smetacek, V.

    In 2009 and 2010, an Indo-German scientific expedition dusted the ocean with iron to stimulate the biological pump that captures atmosphereic carbon dioxide. Two onboard scientists tell the story of this controversial project. Besides raising...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... endoscopy or colonoscopy, to stop bleeding. Healthy lifestyle changes To help you meet your daily recommended iron ... doctor may recommend that you: Adopt healthy lifestyle changes such as heart-healthy eating patterns. Increase your ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Leadership Scientific Divisions Operations and Administration Advisory Committees Budget and Legislative Information Jobs and Working at the ... girls. From birth to 6 months, babies need 0.27 mg of iron. This number goes up ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... screen for iron-deficiency anemia, your doctor may order a blood test called a complete blood count ( ... your risk factors , do a physical exam, or order blood tests or other diagnostic tests. Physical exam ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... duodenum, the first part of the small intestine just beyond the stomach. Even if you have enough ... clamping of your newborn’s umbilical cord at the time of delivery. This may help prevent iron-deficiency ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... less than 12 g/dl for women is diagnostic of anemia. In iron-deficiency anemia, red blood ... both full-term and preterm infants. Look for Diagnosis will explain tests and procedures that your doctor ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... less than 12 g/dl for women is diagnostic of anemia. In iron-deficiency anemia, red blood ... physical exam, or order blood tests or other diagnostic tests. Physical exam Your doctor may ask about ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... improved health for people with iron-deficiency anemia. Recipient Epidemiology Donor Studies program findings help to protect blood donors . NHLBI’s Recipient Epidemiology Donor Studies (REDS) program , which began in ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... a frequent blood donor living in New York City? This study is looking at how iron-deficiency ... frequently. This study is located in New York City, and is recruiting by invitation only. View more ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough ... prevent complications such as abnormal heart rhythms and depression. Learn the warning signs of serious complications and ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... be at risk for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for ... Surgery, upper endoscopy or colonoscopy, to stop bleeding. Healthy lifestyle changes To help you meet your daily ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Operations and Administration Advisory Committees Budget and Legislative Information Jobs and Working at the NHLBI Contact and ... to improve health, and where to find more information. Causes Your body needs iron to make healthy ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia. Learn about the current and future NHLBI efforts to improve health through research and ... blood donors. Cardiovascular Health Study identifies predictors of future health problems in older adults. The NHLBI-sponsored ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Safety Sleep Science and Sleep Disorders Lung Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, ... iron-deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... symptoms. More severe iron-deficiency anemia may cause fatigue or tiredness, shortness of breath, or chest pain. ... in the hands and feet Difficulty concentrating Dizziness Fatigue, or feeling tired, is the most common symptom. ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... to find the energy to do normal activities. Headache Irregular heartbeat. This is a sign of more ... to receive IV iron. You may experience vomiting, headache, or other side effects right after the IV ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... technology commercialization through the Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Our support of SBIR/STTR programs is helping advance research in iron- ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... on your age, sex, and whether you are pregnant or breastfeeding. Recommended daily iron intake for children ... 51, both men and women need 8 mg. Pregnant women need 27 mg. Breastfeeding girls under age ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Treatment will explain treatment-related complications or side effects. Diagnosis Iron-deficiency anemia may be detected during ... to your doctor if you are experiencing side effects such as a bad metallic taste, vomiting, diarrhea, ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... an increased risk for iron-deficiency anemia because of your age, unhealthy environments, family ... 12 months, especially if they are fed only breast milk or are fed formula that is not fortified ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... activity. Older adults, who are more likely to fall, should be especially cautious when resuming activities. Reminders ... develop new therapies for conditions that affect the balance of iron in the body and lead to ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... blood tests, especially in infants and small children Heavy menstrual periods Injury or surgery Urinary tract bleeding ... of iron-deficiency anemia from trauma, surgery, or heavy menstrual periods. Individuals with a gene for hemophilia, ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... interferes with the body’s ability to make hemoglobin. Family history and genetics Von Willebrand disease is an ... develop new therapies for conditions that affect the balance of iron in the body and lead to ...

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Individuals with a gene for hemophilia, including symptomatic female carriers who have heavy menstrual periods, may be ... anemia. Endurance activities and athletes. Athletes, especially young females, are at risk for iron deficiency. Endurance athletes ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... have increased need for iron during growth spurts. Older adults, especially those over age 65. Unhealthy environments Children ... when resuming certain activities, such as physical activity. Older adults, who are more likely to fall, should be ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ... heavy menstrual bleeding, your doctor will want to control these other conditions to prevent you from developing ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies Women’s ... different ages and stages of life. Until the teen years, the recommended amount of iron is the ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... breastfeeding women older than 18 need 9 mg. Problems absorbing iron Even if you consume the recommended ... anemia may cause the following complications: Depression Heart problems. If you do not have enough hemoglobin-carrying ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... lead to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. People who have chronic kidney disease also often take other medicines—such as ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron to support the growth of their unborn babies, so their bodies produce more blood. With ... your doctor may recommend you eat heart-healthy foods or control other conditions that ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... may be at risk for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk ... upper endoscopy or colonoscopy, to stop bleeding. Healthy lifestyle changes To help you meet your daily recommended ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Willebrand disease is an inherited bleeding disorder that affects the blood’s ability to clot. This makes it ... could help develop new therapies for conditions that affect the balance of iron in the body and ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Chest pain Coldness in the hands and feet Difficulty concentrating Dizziness Fatigue, or feeling tired, is the ... Our support of SBIR/STTR programs is helping advance research in iron-deficiency anemia, in part by ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... infancy has lasting effects. We are interested in learning how having iron-deficiency anemia early in life ... Customer Service/Center for Health Information Email Alerts Jobs and Careers Site Index About NHLBI National Institute ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... if you experience heavy periods. During pregnancy, after delivery, or when breastfeeding you may be consuming less ... store iron to prepare for blood loss during delivery. Screening and Prevention Your doctor may screen you ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... dark green leafy vegetables. Foods rich in vitamin C, such as oranges, strawberries, and tomatoes, may help ... has used up. Increase your intake of vitamin C to help your body absorb iron. Avoid drinking ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... through research and scientific discovery. Improving health with current research Learn about the following ways that NHLBI continues to translate current research into improved health for people with iron- ...

  17. Accelerated approval of oncology products: the food and drug administration experience.

    Science.gov (United States)

    Johnson, John R; Ning, Yang-Min; Farrell, Ann; Justice, Robert; Keegan, Patricia; Pazdur, Richard

    2011-04-20

    We reviewed the regulatory history of the accelerated approval process and the US Food and Drug Administration (FDA) experience with accelerated approval of oncology products from its initiation in December 11, 1992, to July 1, 2010. The accelerated approval regulations allowed accelerated approval of products to treat serious or life-threatening diseases based on surrogate endpoints that are reasonably likely to predict clinical benefit. Failure to complete postapproval trials to confirm clinical benefit with due diligence could result in removal of the accelerated approval indication from the market. From December 11, 1992, to July 1, 2010, the FDA granted accelerated approval to 35 oncology products for 47 new indications. Clinical benefit was confirmed in postapproval trials for 26 of the 47 new indications, resulting in conversion to regular approval. The median time between accelerated approval and regular approval of oncology products was 3.9 years (range = 0.8-12.6 years) and the mean time was 4.7 years, representing a substantial time savings in terms of earlier availability of drugs to cancer patients. Three new indications did not show clinical benefit when confirmatory postapproval trials were completed and were subsequently removed from the market or had restricted distribution plans implemented. Confirmatory trials were not completed for 14 new indications. The five longest intervals from receipt of accelerated approval to July 1, 2010, without completion of trials to confirm clinical benefit were 10.5, 6.4, 5.5, 5.5, and 4.7 years. The five longest intervals between accelerated approval and successful conversion to regular approval were 12.6, 9.7, 8.1, 7.5, and 7.4 years. Trials to confirm clinical benefit should be part of the drug development plan and should be in progress at the time of an application seeking accelerated approval to prevent an ineffective drug from remaining on the market for an unacceptable time.

  18. Iron and Prochlorococcus

    Science.gov (United States)

    2009-06-01

    including: acid -cleaned filters, filters rinsed with un-amended trace-metal clean seawater, and filters rinsed with the oxalate solution followed by...greatly influenced by the sources of iron to the marine environment, which include riverine input, hydrothermal upwelling, and atmospheric...deposition (Jickells et al, 2005). While the amount of iron introduced to the oceans from riverine and hydrothermal sources is high, precipitation occurs

  19. Iron-Air Rechargeable Battery

    Science.gov (United States)

    Narayan, Sri R. (Inventor); Prakash, G.K. Surya (Inventor); Kindler, Andrew (Inventor)

    2014-01-01

    Embodiments include an iron-air rechargeable battery having a composite electrode including an iron electrode and a hydrogen electrode integrated therewith. An air electrode is spaced from the iron electrode and an electrolyte is provided in contact with the air electrode and the iron electrodes. Various additives and catalysts are disclosed with respect to the iron electrode, air electrode, and electrolyte for increasing battery efficiency and cycle life.

  20. Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging.

    Science.gov (United States)

    Unterweger, Harald; Janko, Christina; Schwarz, Marc; Dézsi, László; Urbanics, Rudolf; Matuszak, Jasmin; Őrfi, Erik; Fülöp, Tamás; Bäuerle, Tobias; Szebeni, János; Journé, Clément; Boccaccini, Aldo R; Alexiou, Christoph; Lyer, Stefan; Cicha, Iwona

    2017-01-01

    Iron oxide-based contrast agents have been in clinical use for magnetic resonance imaging (MRI) of lymph nodes, liver, intestines, and the cardiovascular system. Superparamagnetic iron oxide nanoparticles (SPIONs) have high potential as a contrast agent for MRI, but no intravenous iron oxide-containing agents are currently approved for clinical imaging. The aim of our work was to analyze the hemocompatibility and immuno-safety of a new type of dextran-coated SPIONs (SPIONdex) and to characterize these nanoparticles with ultra-high-field MRI. Key parameters related to nanoparticle hemocompatibility and immuno-safety were investigated in vitro and ex vivo. To address concerns associated with hypersensitivity reactions to injectable nanoparticulate agents, we analyzed complement activation-related pseudoallergy (CARPA) upon intravenous administration of SPIONdex in a pig model. Furthermore, the size-tunability of SPIONdex and the effects of size reduction on their biocompatibility were investigated. In vitro, SPIONdex did not induce hemolysis, complement or platelet activation, plasma coagulation, or leukocyte procoagulant activity, and had no relevant effect on endothelial cell viability or endothelial-monocytic cell interactions. Furthermore, SPIONdex did not induce CARPA even upon intravenous administration of 5 mg Fe/kg in pigs. Upon SPIONdex administration in mice, decreased liver signal intensity was observed after 15 minutes and was still detectable 24 h later. In addition, by changing synthesis parameters, a reduction in particle size contrast agent.

  1. Iron isomaltoside 1000: a new intravenous iron for treating iron deficiency in chronic kidney disease

    DEFF Research Database (Denmark)

    Wikström, Björn; Bhandari, Sunil; Barany, Peter

    2011-01-01

    Patients with chronic kidney disease (CKD) often suffer from iron deficiency anemia necessitating treatment with intravenous iron. This study was designed to assess the safety of iron isomaltoside 1000 (Monofer) in CKD patients. The secondary objective was to assess its effect on iron deficiency...... anemia....

  2. Anemia and iron deficiency before and after bariatric surgery.

    Science.gov (United States)

    Salgado, Wilson; Modotti, Caue; Nonino, Carla Barbosa; Ceneviva, Reginaldo

    2014-01-01

    Iron deficiency and anemia are changes often associated with obesity. Bariatric surgery is responsible for increasing the iron loss and reducing its absorption. The objective of this study was to evaluate anemia and iron deficiency before and after bariatric surgery and to relate them to possible predisposing factors. A retrospective study was conducted on obese patients submitted to open Roux-en-Y gastric bypass, in which clinical and laboratory data were obtained up to 48 months postoperatively. Patients were divided into groups according to the presence or absence of anemia and to the presence or absence of iron deficiency (even without anemia), and all data were compared between these groups. Preoperatively, 21.5% of patients had anemia and 20% had iron deficiency. The number of patients with anemia did not vary through the 4 years of the study, but ferritin levels significantly decreased with time (Panemia. Female gender was a variable associated with a greater incidence of iron deficiency. Anemia and iron deficiency are frequent in obese patients and must be treated before surgery. Medical and nutritional surveillance is important in the postoperative period of bariatric surgery. Management of each condition must be directed at correcting the 2 major sources of iron deficiency and anemia: food intolerance (mostly meat intolerance) and losses (frequently due to menstruation). These are the factors more related to iron deficient anemia. Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  3. Transient Ischemic Attack Caused by Iron Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    Ufuk Emre

    2006-02-01

    Full Text Available Transient Ischemic Attack Caused by Iron Deficiency Anemia Transient ischemic attacks are episodes of transient focal ischemia involving the brain or brainstem. They are commonly two to thirty minutes in duration and lasting less than 24 hours. Anemia of iron deficiency isn’t frequently cause for transient ischemic attack. It has been reported as a risk factor for childhood ischemic strokes. In the iron deficiency anemia, T‹A may develop as result of hypercoagulable state and increased viscosity that is caused by anemic hypoxia that is result of reduce hemoglobine level, seconder thrombosis and microcytose As iron deficiency anemia has been reported so rarely in adult patients with transient ischemic attacks as a cause, we aimed to discuss the clinical and outcome features of two cases with iron deficiency anemia and transient ischemic attacks in this study. Materials and methods: Routine neurologic examination, biochemical screen, serological tests, vasculitic markers, thyroid function tests, vitamin B 12 level, cranial imaging, vertebral carotid doppler USG examination was conducted in the two patients. Anemia of iron deficiency was found as the only risk factor for TIA and the two patients were treated with replacement of iron and antiagregan therapy. Neurological examination revealed no abnormality through the two years of follow-up. The iron deficiency anemia may be cause of many neurologic problems such a irritability, lethargy, headache, development retardation except from T‹A. In the iron deficiency anemia, early diagnosis and treatment is important

  4. Iron-dependent gene expression in Actinomyces oris

    Directory of Open Access Journals (Sweden)

    Matthew P. Mulé

    2015-12-01

    Results: When A. oris was grown under iron-limiting conditions, the genes encoding iron/siderophore transporters fetA and sidD showed increased expression. One of these genes (sidD was mutated, and the sidD::Km strain exhibited a 50% reduction in growth in late log and stationary phase cells in media that contained iron. This growth defect was restored when the sidD gene was provided in a complemented strain. We were able to isolate the AmdR-encoding gene in seven clinical isolates of Actinomyces. When these protein sequences were aligned to the laboratory strain, there was a high degree of sequence similarity. Conclusions: The growth of the sidD::Km mutant in iron-replete medium mirrored the growth of the wild-type strain grown in iron-limiting medium, suggesting that the sidD::Km mutant was compromised in iron uptake. The known iron regulator AmdR is well conserved in clinical isolates of A. oris. This work provides additional insight into iron metabolism in this important oral microbe.

  5. The NIMO Scandinavian Study: A Prospective Observational Study of Iron Isomaltoside Treatment in Patients with Iron Deficiency

    Directory of Open Access Journals (Sweden)

    Svein Oskar Frigstad

    2017-01-01

    Full Text Available Background. Intravenous iron allows for efficient and well-tolerated treatment in iron deficiency and is routinely used in diseases of the gastrointestinal tract. Objective. The aims of this study were to determine the probability of relapse of iron deficiency over time and to investigate treatment routine, effectiveness, and safety of iron isomaltoside. Methods. A total of 282 patients treated with iron isomaltoside were observed for two treatments or a minimum of one year. Results. Out of 282 patients, 82 had Crohn’s disease and 67 had ulcerative colitis. Another 133 patients had chronic blood loss, malabsorption, or malignancy. Patients who received an iron isomaltoside dose above 1000 mg had a 65% lower probability of needing retreatment compared with those given 1000 mg. A clinically significant treatment response was shown, but in 71/191 (37% of patients, anaemia was not corrected. The mean dose given was 1100 mg, lower than the calculated total iron need of 1481 mg. Adverse drug reactions were reported in 4% of patients. Conclusion. Iron isomaltoside is effective with a good safety profile, and high doses reduce the need for retreatment over time. Several patients were anaemic after treatment, indicating that doses were inadequate for full iron correction. This trial is registered with NCT01900197.

  6. The Evolution of Approval Services.

    Science.gov (United States)

    Warzala, Martin

    1994-01-01

    Describes major developments in book approval plans used by academic libraries for acquisition and for information dissemination and document distribution services based on approval-like concepts. Topics addressed include publishers; marketing; the impact of library automation; value-added services; the economic climate; the influence of…

  7. Electronic Approval of Invoices (AEF)

    CERN Document Server

    2004-01-01

    With a view to the simplification of administrative procedures, AS and FI Departments have completed the second phase of the new procedure for the electronic approval of invoices via the EDH application. The aim of this new procedure is to rationalise the invoice approval process, notably by eliminating paper copies from the approval circuit. This will simplify the processing of invoices and facilitate their timely settlement, while at the same time maintaining a high level of security. Phase II includes handling the electronic approval process of invoices whose amounts do not correspond exactly to those of the associated orders. In such cases, budgetary approval is required for the entire invoiced amount. Further information can be obtained at : http://ais.cern.ch/projs/AEF/help/F_help.htm Phase II of the procedure will be introduced gradually with effect from April 2004. Finance Department, Accounts Payable Section Tel: 72295 Organisation and Procedures Tel: 75885 Information Technologies Department,...

  8. Intravenous iron vs blood for acute post-partum anaemia (IIBAPPA): a prospective randomised trial.

    Science.gov (United States)

    Chua, Seng; Gupta, Sarika; Curnow, Jennifer; Gidaszewski, Beata; Khajehei, Marjan; Diplock, Hayley

    2017-12-19

    Acute post-partum anaemia can be associated with significant morbidity including a predisposition for postnatal depression. Lack of clear practice guidelines means a number of women are treated with multiple blood transfusions. Intravenous iron has the potential to limit the need for multiple blood transfusions but its role in the post-partum setting is unclear. IIBAPPA is a multi-centre randomised non-inferiority trial. Women with a primary post-partum haemorrhage (PPH) >1000 mL and resultant haemoglobin (Hb) 5.5-8.0 g/dL after resuscitation with ongoing symptomatic anaemia who are otherwise stable (no active bleeding) are eligible to participate. Patients with sepsis or conditions necessitating rapid Hb restoration are excluded. Eligible participants are randomised to receive a blood transfusion or a single dose of intravenous iron polymaltose calculated using the Ganzoni formula. Primary outcome measures include Hb, Ferritin and C-Reactive Protein levels on Day 7. Secondary outcomes evaluate (i) Hb, Ferritin and CRP levels on Day 14, 28, (ii) anaemia symptoms on Day 0, 7, 14 and 28 using structured health related quality of life questionnaires, (iii) treatment safety by assessing adverse reactions and infection endpoints and (iv) the quantitative impact of anaemia on breast feeding quality using a hospital designed questionnaire. If equivalence in Hb and ferritin levels, symptom scores and safety endpoints is demonstrated, intravenous iron may become the preferred treatment for women with acute post-partum anaemia to minimise transfusion reactions and costs. Australian and New Zealand Clinical Trials Registry: ACTRN12615001370594 on 16th December, 2015 (prospective approval).

  9. Intravenous iron isomaltoside 1000 (Monofer®) reduces postoperative anaemia in preoperatively non-anaemic patients undergoing elective or subacute coronary artery bypass graft, valve replacement or a combination thereof: a randomized double-blind placebo-controlled clinical trial (the PROTECT trial).

    Science.gov (United States)

    Johansson, P I; Rasmussen, A S; Thomsen, L L

    2015-10-01

    This trial explores whether intravenous iron isomaltoside 1000 (Monofer®) results in a better regeneration of haemoglobin levels and prevents anaemia compared to placebo in preoperative non-anaemic patients undergoing cardiac surgery. The trial is a prospective, double-blind, comparative, placebo-controlled trial of 60 non-anaemic patients undergoing cardiac surgery. The patients were randomized 1:1 to either 1000 mg intravenous iron isomaltoside 1000 administered perioperatively by infusion or placebo. Mean preoperative haemoglobin in the active treatment group was 14·3 g/dl vs. 14·0 g/dl in the placebo group. At discharge 5 days after surgery, haemoglobin levels were reduced to 10·7 and 10·5 g/dl, respectively. One month after surgery, haemoglobin concentration had increased to an average of 12·6 g/dl vs. 11·8 g/dl (p = 0·012) and significantly more patients were non-anaemic in the intravenous iron isomaltoside 1000-treated group compared to the placebo group (38·5% vs. 8·0%; p = 0·019). There were no differences in side-effects between the groups. A single perioperative 1000 mg dose of intravenous iron isomaltoside 1000 significantly increased the haemoglobin level and prevented anaemia 4 weeks after surgery, with a short-term safety profile similar to placebo. Future trials on potential clinical benefits of preoperative treatment with intravenous iron in non-anaemic patients are needed. © 2015 The Authors ISBT Science Series published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.

  10. The physiological functions of iron regulatory proteins in iron homeostasis - an update

    Directory of Open Access Journals (Sweden)

    De-Liang eZhang

    2014-06-01

    Full Text Available Iron regulatory proteins (IRPs regulate the expression of genes involved in iron metabolism by binding to RNA stem-loop structures known as iron responsive elements (IREs in target mRNAs. IRP binding inhibits the translation of mRNAs that contain an IRE in the 5’untranslated region of the transcripts, and increases the stability of mRNAs that contain IREs in the 3'untranslated region of transcripts. By these mechanisms, IRPs increase cellular iron absorption and decrease storage and export of iron to maintain an optimal intracellular iron balance. There are two members of the mammalian IRP protein family, IRP1 and IRP2, and they have redundant functions as evidenced by the embryonic lethality of the mice that completely lack IRP expression (Irp1-/-/Irp2-/- mice, which contrasts with the fact that Irp1-/- and Irp2-/- mice are viable. In addition, Irp2-/- mice also display neurodegenerative symptoms and microcytic hypochromic anemia, suggesting that IRP2 function predominates in the nervous system and erythropoietic homeostasis. Though the physiological significance of IRP1 had been unclear since Irp1-/- animals were first assessed in the early 1990’s, recent studies indicate that IRP1 plays an essential function in orchestrating the balance between erythropoiesis and bodily iron homeostasis. Additionally, Irp1-/- mice develop pulmonary hypertension, and they experience sudden death when maintained on an iron-deficient diet, indicating that IRP1 has a critical role in the pulmonary and cardiovascular systems. This review summarizes recent progress that has been made in understanding the physiological roles of IRP1 and IRP2, and further discusses the implications for clinical research on patients with idiopathic polycythemia, pulmonary hypertension and neurodegeneration.

  11. HFE gene: Structure, function, mutations, and associated iron abnormalities.

    Science.gov (United States)

    Barton, James C; Edwards, Corwin Q; Acton, Ronald T

    2015-12-15

    The hemochromatosis gene HFE was discovered in 1996, more than a century after clinical and pathologic manifestations of hemochromatosis were reported. Linked to the major histocompatibility complex (MHC) on chromosome 6p, HFE encodes the MHC class I-like protein HFE that binds beta-2 microglobulin. HFE influences iron absorption by modulating the expression of hepcidin, the main controller of iron metabolism. Common HFE mutations account for ~90% of hemochromatosis phenotypes in whites of western European descent. We review HFE mapping and cloning, structure, promoters and controllers, and coding region mutations, HFE protein structure, cell and tissue expression and function, mouse Hfe knockouts and knockins, and HFE mutations in other mammals with iron overload. We describe the pertinence of HFE and HFE to mechanisms of iron homeostasis, the origin and fixation of HFE polymorphisms in European and other populations, and the genetic and biochemical basis of HFE hemochromatosis and iron overload. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. The safety of available treatment options for iron-deficiency anemia.

    Science.gov (United States)

    Muñoz, Manuel; Gómez-Ramírez, Susana; Bhandari, Sunil

    2018-02-01

    Iron deficiency (ID), with or without anemia, is highly prevalent worldwide and has clinical consequences. The prevention and treatment of ID is a major public health goal. Accurate diagnosis, selection of the appropriate iron replacement therapy and addressing the underlying cause, remain as the main challenges in ID management. Areas covered: This review aims to provide a narrative review of current available evidence on iron supplementation options regularly used to treat ID, including oral and intravenous (IV) iron formulations, with emphasis on safety issues. Analyzed safety concerns include gastrointestinal side effects (oral iron) and risks of hypotension, anaphylaxis, infection, hypophosphatemia, oxidative stress and mortality (IV iron). Expert opinion: Low-to-moderate doses of oral iron supplementation remains as first line therapy for uncomplicated ID, but it has been scarcely discussed in the setting of inflammation. Confirmatory studies on the efficacy of newer oral iron formulations in this setting are needed. Compared with oral iron, short-term IV iron administration is more efficacious in ID correction, without significant safety concerns. However, long-term safety of IV iron maintenance therapy, head to head comparisons of IV iron preparations, pharmacological modulation of hepcidin and HIF, and extra-erythropoietic effects of iron are among the important areas of research.

  13. Health-Related Quality of Life, Treatment Satisfaction, Adherence and Persistence in β-Thalassemia and Myelodysplastic Syndrome Patients with Iron Overload Receiving Deferasirox: Results from the EPIC Clinical Trial

    Directory of Open Access Journals (Sweden)

    John Porter

    2012-01-01

    Full Text Available Treatment of iron overload using deferoxamine (DFO is associated with significant deficits in patients' health-related quality of life (HRQOL and low treatment satisfaction. The current article presents patient-reported HRQOL, satisfaction, adherence, and persistence data from β-thalassemia (n=274 and myelodysplastic syndrome (MDS patients (n=168 patients participating in the Evaluation of Patients' Iron Chelation with Exjade (EPIC study (NCT00171821; a large-scale 1-year, phase IIIb study investigating the efficacy and safety of the once-daily oral iron chelator, deferasirox. HRQOL and satisfaction, adherence, and persistence to iron chelation therapy (ICT data were collected at baseline and end of study using the Medical Outcomes Short-Form 36-item Health Survey (SF-36v2 and the Satisfaction with ICT Questionnaire (SICT. Compared to age-matched norms, β-thalassemia and MDS patients reported lower SF-36 domain scores at baseline. Low levels of treatment satisfaction, adherence, and persistence were also observed. HRQOL improved following treatment with deferasirox, particularly among β-thalassemia patients. Furthermore, patients reported high levels of satisfaction with deferasirox at end of study and greater ICT adherence, and persistence. Findings suggest deferasirox improves HRQOL, treatment satisfaction, adherence, and persistence with ICT in β-thalassemia and MDS patients. Improving such outcomes is an important long-term goal for patients with iron overload.

  14. An iron-57 Moessbauer spectroscopic study of titania-supported iron- and iron-iridium catalysts

    International Nuclear Information System (INIS)

    Berry, F.J.; Jobson, S.

    1992-01-01

    57 Fe Moessbauer spectroscopy shows that titania-supported iron is reduced by treatment in hydrogen at significantly lower temperatures than corresponding silica- and alumina-supported catalysts. The metallic iron formed under hydrogen at 600deg C is partially converted to carbide by treatment in carbon monoxide and hydrogen. In contrast to its alumina- and silica-supported counterparts, the remainder of the titania-supported iron is unchanged by this gaseous mixture. The 57 Fe Moessbauer spectra of EXAFS show that iron and iridium in the titania-supported iron-iridium catalysts are reduced in hydrogen at even lower temperatures and, after treatment at 600deg C, are predominantly present as the iron-iridium alloy. The treatment of these reduced catalysts in carbon monoxide and hydrogen is shown by Moessbauer spectroscopy and EXAFS to induce the segregation of iron from the iron-iridium alloy and its conversion to iron oxide. (orig.)

  15. Dietary iron intake, iron status, and gestational diabetes.

    Science.gov (United States)

    Zhang, Cuilin; Rawal, Shristi

    2017-12-01

    Pregnant women are particularly vulnerable to iron deficiency and related adverse pregnancy outcomes and, as such, are routinely recommended for iron supplementation. Emerging evidence from both animal and population-based studies, however, has raised potential concerns because significant associations have been observed between greater iron stores and disturbances in glucose metabolism, including increased risk of type 2 diabetes among nonpregnant individuals. Yet, the evidence is uncertain regarding the role of iron in the development of gestational diabetes mellitus (GDM), a common pregnancy complication which has short-term and long-term adverse health ramifications for both women and their children. In this review, we critically and systematically evaluate available data examining the risk of GDM associated with dietary iron, iron supplementation, and iron status as measured by blood concentrations of several indicators. We also discuss major methodologic concerns regarding the available epidemiologic studies on iron and GDM. © 2017 American Society for Nutrition.

  16. Mammalian iron metabolism and its control by iron regulatory proteins☆

    Science.gov (United States)

    Anderson, Cole P.; Shen, Lacy; Eisenstein, Richard S.; Leibold, Elizabeth A.

    2013-01-01

    Cellular iron homeostasis is maintained by iron regulatory proteins 1 and 2 (IRP1 and IRP2). IRPs bind to iron-responsive elements (IREs) located in the untranslated regions of mRNAs encoding protein involved in iron uptake, storage, utilization and export. Over the past decade, significant progress has been made in understanding how IRPs are regulated by iron-dependent and iron-independent mechanisms and the pathological consequences of IRP2 deficiency in mice. The identification of novel IREs involved in diverse cellular pathways has revealed that the IRP–IRE network extends to processes other than iron homeostasis. A mechanistic understanding of IRP regulation will likely yield important insights into the basis of disorders of iron metabolism. This article is part of a Special Issue entitled: Cell Biology of Metals. PMID:22610083

  17. Iron deficiency and cognitive functions

    Directory of Open Access Journals (Sweden)

    Jáuregui-Lobera I

    2014-11-01

    Full Text Available Ignacio Jáuregui-Lobera Department of Nutrition and Bromatology, Pablo de Olavide University, Seville, Spain Abstract: Micronutrient deficiencies, especially those related to iodine and iron, are linked to different cognitive impairments, as well as to potential long-term behavioral changes. Among the cognitive impairments caused by iron deficiency, those referring to attention span, intelligence, and sensory perception functions are mainly cited, as well as those associated with emotions and behavior, often directly related to the presence of iron deficiency anemia. In addition, iron deficiency without anemia may cause cognitive disturbances. At present, the prevalence of iron deficiency and iron deficiency anemia is 2%–6% among European children. Given the importance of iron deficiency relative to proper cognitive development and the alterations that can persist through adulthood as a result of this deficiency, the objective of this study was to review the current state of knowledge about this health problem. The relevance of iron deficiency and iron deficiency anemia, the distinction between the cognitive consequences of iron deficiency and those affecting specifically cognitive development, and the debate about the utility of iron supplements are the most relevant and controversial topics. Despite there being methodological differences among studies, there is some evidence that iron supplementation improves cognitive functions. Nevertheless, this must be confirmed by means of adequate follow-up studies among different groups. Keywords: iron deficiency, anemia, cognitive functions, supplementation

  18. Absorption of medicamental iron and iron from food

    International Nuclear Information System (INIS)

    Reizenstein, P.; Carlmark, B.; Ehn, L.; Forsberg, K.; Hoeglund, S.; Terpstra, T.

    1976-01-01

    Methods are reviewed for the measurement of iron absorption. The chemical balance method has been almost entirely supplanted by radioisotope methods, which include notably whole-body counting and measurement of incorporation of radioiron into red cells. A survey is also given of the various conditions that influence iron absorption, including chemical form of iron, amount of iron, accompanying diet. Absorption tests must be conducted under relevant conditions. (author)

  19. Characteristics of efficacy evidence supporting approval of supplemental indications for prescription drugs in United States, 2005-14: systematic review.

    Science.gov (United States)

    Wang, Bo; Kesselheim, Aaron S

    2015-09-23

    To characterize the types of comparators and endpoints used in efficacy trials for approvals of supplemental indications, compared with the data supporting these drugs' originally approved indications. Systematic review. Publicly accessible data on supplemental indications approved by the US Food and Drug Administration from 2005 to 2014. Types of comparators (active, placebo, historical, none) and endpoints (clinical outcomes, clinical scales, surrogate) in the efficacy trials for these drugs' supplemental and original indication approvals. The cohort included 295 supplemental indications. Thirty per cent (41/136) of supplemental approvals for new indications were supported by efficacy trials with active comparators, compared with 51% (47/93) of modified use approvals and 11% (7/65) of approvals expanding the patient population (Pindications, 30% (28/93) of modified indication approvals, and 22% (14/65) of expanded population approvals (P=0.29). Orphan drugs had supplemental approvals for 40 non-orphan indications, which were supported by similar proportions of trials using active comparators (28% (11/40) for non-orphan supplemental indications versus 24% (10/42) for original orphan indications; P=0.70) and clinical outcome endpoints (25% (10/40) versus 31% (13/42); P=0.55). Wide variations were seen in the evidence supporting approval of supplemental indications, with the fewest active comparators and clinical outcome endpoints used in trials leading to supplemental approvals that expanded the patient population. © Wang et al 2015.

  20. Drugs Approved for Kidney (Renal Cell) Cancer

    Science.gov (United States)

    ... Your Treatment Research Drugs Approved for Kidney (Renal Cell) Cancer This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Kidney (Renal Cell) Cancer Afinitor (Everolimus) Aldesleukin Avastin (Bevacizumab) Axitinib Bevacizumab Cabometyx ( ...