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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral infarction in children is often caused by intracranial vascular disorder, cardiac disease, head injury, or infection, and is rarely induced by blood disease. In this paper, we describe an infantile case of cerebral infarction associated with thrombocytosis. A female infant of eight months of age developed left hemiparesis after a slight head injury. Her CT and MRI demonstrated a cerebral infarction located from the right internal capsule to the right corona radiata. Laboratory findings revealed iron-deficiency anemia and thrombocytosis with a platelet count 107.5 x 10(4)/mm3. Although she had no disorder that had caused iron deficiency, serum Fe value of the patient was low with a count of 18 micrograms/dl. Her bone marrow was normal except for a slight increase in the number of megakaryocytes. One month later, her anemia was improved by means of oral iron replacement. However, her platelet count remained at more than 100 x 10(4)/mm3 as it had been before. Her condition of left-sided hemiparesis gradually improved by a program of rehabilitation, and did not recur after aspirin administration. Although the main cause of her thrombocytosis that led to a transient cerebrovascular accident is obscure, it is postulated that her iron deficiency anemia induced secondary thrombocytosis, or else the patient had essential thrombocytosis.
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PMID:[An infantile case of cerebral infarction associated with thrombocytosis]. 159 Oct 25

Restless Legs Syndrome (RLS) is a disorder of sensation with a prevalence of around 2-5% of the population. Relevant to understanding the possible pathophysiological mechanism is the fact that RLS is extremely responsive to dopaminergic agents. A second issue is that iron deficiency states may precipitate RLS in as much as 25-30% of people with iron deficiency. Studies looking at basal ganglia dopaminergic function using PET and SPECT techniques have shown a decrease in binding potential for the dopamine receptor and transporter. Similar phenomena occurs in iron-deficient animals. Using MRI techniques and CSF analysis of iron-related protein, studies have suggested a reduction in brain iron concentration occurs in RLS patients. The relevance of CNS iron metabolism to the pathophysiology of RLS is discussed.
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PMID:Insight into the pathophysiology of restless legs syndrome. 1110

In the past seven years numerous genes that influence iron homeostasis have been discovered. Dr. Beutler provides a brief overview of these genes, genes that encode HFE, DMT-1, ferroportin, transferrin receptor 2, hephaestin, and hepcidin to lay the groundwork for a discussion of the various clinical forms of iron storage disease and how they differ from one another. In Section I, Dr. Beutler also discusses the types of hemochromatosis that exist as acquired and as hereditary forms. Acquired hemochromatosis occurs in patients with marrow failure, particularly when there is active ineffective erythropoiesis. Hereditary hemochromatosis is most commonly due to mutations in the HLA-linked HFE gene, and hemochromatosis clinically indistinguishable from HFE hemochromatosis is the consequence of mutations in three transferrin receptor-2 gene. A more severe, juvenile form of iron storage disease results from mutations of the gene encoding hepcidin or of a not-yet-identified gene on chromosome 1q. Autosomal dominant iron storage disease is a consequence of ferroportin mutations, and a polymorphism in the ferroportin gene appears to be involved in the African iron overload syndrome. Evidence regarding the biochemical and clinical penetrance of hemochromatosis due to mutations of the HFE gene is rapidly accumulating. These studies, emanating from several centers in Europe and the United States, all agree that the penetrance of hemochromatosis is much lower than had previously been thought. Probably only 1% of homozygotes develop clinical findings. The implications of these new findings for the management of hemochromatosis will be discussed. In Section II, Dr. Victor Hoffbrand discusses the management of iron storage disease by chelation therapy, treatment that is usually reserved for patients with secondary hemochromatosis such as occurs in the thalassemias and in patients with transfusion requirements due to myelodysplasia and other marrow failure states. Tissue iron can be estimated by determining serum ferritin levels, measuring liver iron, and by measuring cardiac iron using the MRI-T2* technique. The standard form of chelation therapy is the slow intravenous or subcutaneous infusion of desferoxamine. An orally active bidentate iron chelator, deferiprone, is now licensed in 25 countries for treatment of patients with thalassemia major. Possibly because of the ability of this compound to cross membranes, it appears to have superior cardioprotective properties. Agranulocytosis is the most serious complication of deferiprone therapy and occurs in about 1% of treated patients. Deferiprone and desferoxamine can be given together or on alternating schedules. A new orally active chelating agent ICL 670 seems promising in early clinical studies. In Section III, Dr. James Cook discusses the most common disorder of iron homeostasis, iron deficiency. He will compare some of the standard methods for identifying iron deficiency, the hemoglobin level, transferrin saturation, and mean corpuscular hemoglobin and compare these with some of the newer methods that have been introduced, specifically the percentage of hypochromic erythrocytes and reticulocyte hemoglobin content. The measurement of storage iron is achieved by measuring serum ferritin levels. The soluble transferrin receptor is a truncated form of the cellular transferrin receptor and the possible value of this measurement in the diagnosis of iron deficiency will be discussed. Until recently iron dextran was the only parental iron preparation available in the US. Sodium ferric gluconate, which has been used extensively in Europe for many years, is now available in the United States. It seems to have a distinct advantage over iron dextran in that anaphylactic reactions are much less common with the latter preparation.
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PMID:Iron deficiency and overload. 1463 76

Preliminary but increasing evidence suggests that attention-deficit/hyperactivity disorder (ADHD), Tourette's syndrome (TS), and restless legs syndrome (RLS) may be comorbid. In the present article, we hypothesize that ADHD, TS, and RLS may be part of a spectrum, and that iron deficiency contributes to the pathophysiology underlying this spectrum. Iron deficiency might lead to ADHD, RLS and TS symptoms via its impact on the metabolism of dopamine and other catecholamines, which have been involved into the pathophysiology of ADHD, TS, and RLS. We speculate that the catecholaminergic systems are differently impacted in each of the three disorders, contributing to a different specific phenotypic expression of iron deficiency. MRI studies assessing brain iron levels in ADHD, TS, and childhood RLS, as well as genetic studies on the specific molecular pathways involved in iron deficiency, are greatly needed to confirm the iron hypothesis underlying ADHD, TS, and RLS. This body of research may set the basis for controlled trials assessing the effectiveness and tolerability, as well as the most appropriate dose, duration and type (oral vs. intravenous) of iron supplementation. In conclusion, the iron hypothesis may help us progress in the understanding of pathophysiological links between ADHD, RLS, and TS, suggesting that iron supplementation might be effective for all these three impairing conditions.
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PMID:Attention-deficit/hyperactivity disorder, Tourette's syndrome, and restless legs syndrome: the iron hypothesis. 1816 40

Attention-deficit/hyperactivity disorder is a neurobiological syndrome with an estimated prevalence among children and adolescents of 5%. It is a highly heritable disorder, but acquired factors in etiology are sometimes uncovered that may be amenable to preventive measures or specific therapy. Early reports have described symptoms similar to attention-deficit/hyperactivity disorder that followed brain trauma or viral encephalitis, and recent MRI studies have demonstrated brain volumetric changes that may be involved in the pathophysiology of the syndrome. The American Psychiatric Association's Diagnostic Statistical Manual, introduced in 1968, emphasizes symptomatic criteria in diagnosis. Here, an overview of environmental factors in the etiology of attention-deficit/hyperactivity disorder is presented to encourage more emphasis and research on organic causal factors, preventive intervention, and specific therapies. An organic theory and the genetic and biochemical basis of attention-deficit/hyperactivity disorder are briefly reviewed, and an etiologic classification is suggested. Environmental factors are prenatal, perinatal, and postnatal in origin. Pregnancy- and birth-related risk factors include maternal smoking and alcohol ingestion, prematurity, hypoxic-ischemic encephalopathy, and thyroid deficiency. Childhood illnesses associated with attention-deficit/hyperactivity disorder include virus infections, meningitis, encephalitis, head injury, epilepsy, toxins, and drugs. More controversial factors discussed are diet-related sensitivities and iron deficiency. Early prenatal recognition, prevention, and treatment of environmental etiologies of attention-deficit/hyperactivity disorder may reduce physician reliance on symptomatic modification with medication, a frequent reason for parental concern.
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PMID:Etiologic classification of attention-deficit/hyperactivity disorder. 1824 8

Evidence for tissue iron deficiency in restless legs syndrome (RLS) is limited to the substantia nigra (SN). Using MRI, we assessed T2 values of various brain regions in 6 RLS patients and 19 controls and correlated them with sonographically assessed SN echogenicity. Both neuroimaging features are supposed to correlate with tissue iron content. Mean T2 values of all regions were higher in patients (2.9-7.8%), though significantly increased only in four regions; the mean T2 over all voxels was higher in patients (5.1%, P < 0.001) and correlated inversely with SN echogenicity (r = -0.61, P < 0.001). This indicates multiregional (global) brain iron deficiency in RLS and proposes SN echogenicity as a potential morphological marker for brain iron status. (c) 2008 Movement Disorder Society.
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PMID:Multiregional brain iron deficiency in restless legs syndrome. 1844 25

Restless legs syndrome (RLS) is a sensorimotor disorder that is frequently associated with periodic leg movements (PLMS). RLS is generally considered to be a central nervous system (CNS)-related disorder although no specific lesion has been found to be associated with the syndrome. Reduced intracortical inhibition has been demonstrated in RLS by transcranial magnetic stimulation. Some MRI studies have revealed the presence of morphologic changes in the somatosensory cortex, motor cortex and thalamic gray matter. The results of SPECT and PET studies showed that the limbic and opioid systems also play important roles in the pathophysiology of RLS. A functional MRI study revealed abnormal bilateral cerebellar and thalamic activation during the manifestation of sensory symptoms, with additional red nucleus and reticular formation activity during PLMS. PLMS is likely to occur in patients with spinal cord lesions, and some patients with sensory polyneuropathy may exhibit RLS symptoms. RLS symptoms seem to depend on abnormal spinal sensorimotor integration at the spinal cord level and abnormal central somatosensory processing. PLMS appears to depend on increased excitability of the spinal cord and a decreased supraspinal inhibitory mechanism from the All diencephalic dopaminergic system. RLS symptoms respond very dramatically to dopaminergic therapy. The results of analysis by PET and SPECT studies of striatal D2 receptor binding in humans are inconclusive. However, studies in animal models suggest that the participation of the All dopaminergic system and the D3 receptor in RLS symptoms. The symptoms of RLS are aggravated in those with iron deficiency, and iron treatment ameliorates the symptoms in some patients. Neuroimaging studies, analysis of the cerebrospinal fluid, and studies on postmortem tissue and use of animal models have indicated that low brain iron concentrations and dysfunction of iron metabolism and intracellular iron may play key roles in the pathogenesis of RLS. The "iron-dopamine model" explains that iron deficiency in the brain causes an abnormality in the dopaminergic system leading to manifestation of RLS. Genetic factors are also important in the development of RLS. A positive family history for RLS has been reported by 40% to 60% of RLS patients. Five loci (RLS 1: 12q, RLS 2: 14q, RLS 3: 9p, RLS 4: 2q, RLS 5: 20p) have been described. Genome-wide association studies have identified variants within the intronic or intergenetic regions of MEIS1 (2p), LBXCOR1/MAP2K5 (15q), BTBD9 (6p), neuronal nitric oxide synthase (NOS1) (12q) and protein tyrosine phosphatase receptor type delta (9p) genes. In conclusion, disturbances in the central dopaminergic system, disturbances in iron metabolism, and genetics seem to be the primary factors in the pathophysiology of RLS.
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PMID:[Pathophysiology of restless legs syndrome]. 1951 12

A 13-year-old female presented with complaints of headache, vomiting, diplopia and progressive blurring of vision developing sequentially over 1 month. Examination revealed marked pallor and bilateral lateral rectus palsy with a visual acuity of 6/12 and 6/36 in the left and the right eye, respectively. Fundus examination showed late stage papilloedema in both eyes. Investigation for anaemia revealed severe iron deficiency. MRI of the brain was normal. The cerebrospinal fluid opening pressure was markedly raised at 320 mm of water but fluid analysis did not reveal any abnormality. Thus, a diagnosis of iron deficiency anaemia with idiopathic intracranial hypertension was made. The patient responded dramatically to intravenous iron treatment. Physicians must be aware of this rare presentation of the common problem of iron deficiency, the rapid correction of which plays an instrumental role in salvaging the patient's vision and preventing a recurrence of disease.
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PMID:Iron deficiency masquerading as idiopathic intracranial hypertension. 2168 48

Stem cell based therapies offer significant potential for the field of regenerative medicine. However, much remains to be understood regarding the in vivo kinetics of transplanted cells. A non-invasive method to repetitively monitor transplanted stem cells in vivo would allow investigators to directly monitor stem cell transplants and identify successful or unsuccessful engraftment outcomes. A wide range of stem cells continues to be investigated for countless applications. This protocol focuses on 3 different stem cell populations: human embryonic kidney 293 (HEK293) cells, human mesenchymal stem cells (hMSC) and induced pluripotent stem (iPS) cells. HEK 293 cells are derived from human embryonic kidney cells grown in culture with sheared adenovirus 5 DNA. These cells are widely used in research because they are easily cultured, grow quickly and are easily transfected. hMSCs are found in adult marrow. These cells can be replicated as undifferentiated cells while maintaining multipotency or the potential to differentiate into a limited number of cell fates. hMSCs can differentiate to lineages of mesenchymal tissues, including osteoblasts, adipocytes, chondrocytes, tendon, muscle, and marrow stroma. iPS cells are genetically reprogrammed adult cells that have been modified to express genes and factors similar to defining properties of embryonic stem cells. These cells are pluripotent meaning they have the capacity to differentiate into all cell lineages. Both hMSCs and iPS cells have demonstrated tissue regenerative capacity in-vivo. Magnetic resonance (MR) imaging together with the use of superparamagnetic iron oxide (SPIO) nanoparticle cell labels have proven effective for in vivo tracking of stem cells due to the near microscopic anatomical resolution, a longer blood half-life that permits longitudinal imaging and the high sensitivity for cell detection provided by MR imaging of SPIO nanoparticles. In addition, MR imaging with the use of SPIOs is clinically translatable. SPIOs are composed of an iron oxide core with a dextran, carboxydextran or starch surface coat that serves to contain the bioreactive iron core from plasma components. These agents create local magnetic field inhomogeneities that lead to a decreased signal on T2-weighted MR images. Unfortunately, SPIOs are no longer being manufactured. Second generation, ultrasmall SPIOs (USPIO), however, offer a viable alternative. Ferumoxytol (FerahemeTM) is one USPIO composed of a non-stoichiometric magnetite core surrounded by a polyglucose sorbitol carboxymethylether coat. The colloidal, particle size of ferumoxytol is 17-30 nm as determined by light scattering. The molecular weight is 750 kDa, and the relaxivity constant at 2T MRI field is 58.609 mM(-1) sec(-1) strength. Ferumoxytol was recently FDA-approved as an iron supplement for treatment of iron deficiency in patients with renal failure. Our group has applied this agent in an "off label" use for cell labeling applications. Our technique demonstrates efficient labeling of stem cells with ferumoxytol that leads to significant MR signal effects of labeled cells on MR images. This technique may be applied for non-invasive monitoring of stem cell therapies in pre-clinical and clinical settings.
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PMID:Labeling stem cells with ferumoxytol, an FDA-approved iron oxide nanoparticle. 2208 87

Control of iron homeostasis is essential for healthy central nervous system function: iron deficiency is associated with cognitive impairment, yet iron overload is thought to promote neurodegenerative diseases. Specific genetic markers have been previously identified that influence levels of transferrin, the protein that transports iron throughout the body, in the blood and brain. Here, we discovered that transferrin levels are related to detectable differences in the macro- and microstructure of the living brain. We collected brain MRI scans from 615 healthy young adult twins and siblings, of whom 574 were also scanned with diffusion tensor imaging at 4 Tesla. Fiber integrity was assessed by using the diffusion tensor imaging-based measure of fractional anisotropy. In bivariate genetic models based on monozygotic and dizygotic twins, we discovered that partially overlapping additive genetic factors influenced transferrin levels and brain microstructure. We also examined common variants in genes associated with transferrin levels, TF and HFE, and found that a commonly carried polymorphism (H63D at rs1799945) in the hemochromatotic HFE gene was associated with white matter fiber integrity. This gene has a well documented association with iron overload. Our statistical maps reveal previously unknown influences of the same gene on brain microstructure and transferrin levels. This discovery may shed light on the neural mechanisms by which iron affects cognition, neurodevelopment, and neurodegeneration.
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PMID:Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene. 2223 60


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