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Iron Deposition (iron + deposition)
Selected AbstractsIncreased QT variability in young asymptomatic patients with ,-thalassemia majorEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2007Damiano Magrě Abstract Background:, Despite recent progress in iron chelation therapy, sudden cardiac death due to malignant ventricular arrhythmias remains a vexing, clinical problem in patients with ,-thalassemia major (TM). In this study we assessed whether the major indices of QT variability, emerging tools for risk stratification of sudden cardiac death, differ in young asymptomatic patients with TM and healthy persons. Methods: Thirty patients with TM and 30 healthy control subjects underwent a 5-min electrocardiography recording to calculate the following variables: QT variance (QTv), QTv normalized for mean QT (QTVN) and QT variability index (QTVI). All subjects also underwent a two-dimensional and Doppler echocardiography study and magnetic resonance imaging (MRI) to determine cardiac and hepatic T2* values. Results: No differences were observed in clinical and conventional echo-Doppler findings in healthy control subjects and patients with TM whereas QTv, QTVN and QTVI values were significantly higher in patients than those in controls (QTv, P < 0.001; QTVN, P < 0.05 and QTVI, P < 0.001) and cardiac T2* and hepatic MRI T2* values were significantly lower in patients with TM (P < 0.001). The indices of temporal QT variability correlated significantly with MRI data. Conclusions: Young asymptomatic patients with TM have increased cardiac repolarization variability as assessed by QT variability indices, probably due to cardiac iron deposition. These easily assessed, non-invasive markers could be used to identify increased myocardial repolarization lability early in asymptomatic patients with TM. [source] Pathogenesis of haemophilic synovitis: experimental studies on blood-induced joint damageHAEMOPHILIA, Issue 2007L. A. VALENTINO Summary., Hemarthrosis is a common manifestation of haemophilia, and joint arthropathy remains a frequent complication. Even though the exact mechanisms related to blood-induced joint disease have not yet been fully elucidated, it is likely that iron deposition in the synovium induces an inflammatory response that causes not only immune system activation but also stimulates angiogenesis. This process ultimately results in cartilage and bone destruction. Investigating the processes that occur in the early stages of blood-induced joint disease in humans has been very limited. Therefore, the use of haemophilic animal models is critical to augment the understanding of this phenomenon. This article discusses three cellular regulators (p53, p21 and TRAIL) induced in synovial tissue that are important for iron metabolism. A cartilage remodelling programme induced by the release of cytokines and growth factors that result in articular damage is also discussed. Full elucidation of the pathogenesis of haemophilic joint disease is required to identify new avenues for prevention and therapy. [source] Serum amino-terminal propeptide of type III procollagen and 7S domain of type IV collagen correlate with hepatic iron concentration in patients with chronic hepatitis C following ,-interferon therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2001Ichiro Shimizu Abstract Background: It has been reported that chronic infection with hepatitis C virus is associated with excess iron deposits in the liver of subjects who are neither alcoholics nor recipients of blood transfusions. However, little is known about the relationship between hepatic iron concentration (HIC) and the serum levels of hepatic fibrogenesis markers, which were caused by interferon therapy for chronic hepatitis C. Therefore, changes in the serum amino-terminal propeptide of type III procollagen (P-III-P) and the 7S domain of type IV collagen (7S-IV) in 16 patients treated with ,-interferon (IFN-,) were studied, and their HIC and histological assessment evaluated. Hepatic iron concentrations were measured by using liver biopsy specimens obtained before and 6 months after the cessation of treatment. Methods and Results: Eight subjects (50%) who had normal alanine transaminase levels at 6 months after therapy showed significantly lowered HIC, and attenuated hepatic iron staining with decreased serum levels of P-III-P and 7S-IV compared to the remaining subjects. The HIC was significantly correlated with the serum levels of P-III-P and 7S-IV in all subjects. Conclusions: These findings suggest that IFN-, treatment may decrease stimuli for fibrogenesis, at least in part, by reducing the hepatic iron deposition in patients with chronic hepatitis C. [source] Astroglia overexpressing heme oxygenase-1 predispose co-cultured PC12 cells to oxidative injury,JOURNAL OF NEUROSCIENCE RESEARCH, Issue 10 2007Linyang Song Abstract The mechanisms responsible for the progressive degeneration of dopaminergic neurons and pathologic iron deposition in the substantia nigra pars compacta of patients with Parkinson's disease (PD) remain unclear. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in the oxidative degradation of heme to ferrous iron, carbon monoxide, and biliverdin, is upregulated in affected PD astroglia and may contribute to abnormal mitochondrial iron sequestration in these cells. To determine whether glial HO-1 hyper-expression is toxic to neuronal compartments, we co-cultured dopaminergic PC12 cells atop monolayers of human (h) HO-1 transfected, sham-transfected, or non-transfected primary rat astroglia. We observed that PC12 cells grown atop hHO-1 transfected astrocytes, but not the astroglia themselves, were significantly more susceptible to dopamine (1 ,M) + H2O2 (1 ,M)-induced death (assessed by nuclear ethidium monoazide bromide staining and anti-tyrosine hydroxylase immunofluorescence microscopy) relative to control preparations. In the experimental group, PC12 cell death was attenuated significantly by the administration of the HO inhibitor, SnMP (1.5 ,M), the antioxidant, ascorbate (200 ,M), or the iron chelators, deferoxamine (400 ,M), and phenanthroline (100 ,M). Exposure to conditioned media derived from HO-1 transfected astrocytes also augmented PC12 cell killing in response to dopamine (1 ,M) + H2O2 (1 ,M) relative to control media. In PD brain, overexpression of HO-1 in nigral astroglia and accompanying iron liberation may facilitate the bioactivation of dopamine to neurotoxic free radical intermediates and predispose nearby neuronal constituents to oxidative damage. © 2007 Wiley-Liss, Inc. [source] Liver pathology in compound heterozygous patients for hemochromatosis mutationsLIVER INTERNATIONAL, Issue 4 2002Maximilian Schöniger-Hekele Abstract: Background: While hepatic pathology of homozygous carriers of the C282Y mutation of the HFE haemochromatosis gene is well defined, the impact of the C282Y/H63D compound heterozygous carrier state is unknown. Aims: To evaluate the range of hepatic pathology in C282Y/H63D compound heterozygous patients. Patients: 25 C282Y/H63D compound heterozygous patients with and without known underlying liver disease underwent liver biopsies for evaluation or abnormal liver tests. Eleven cadaveric liver donors with HFE wild type served as controls. Methods: Mutations in the HFE gene were detected by polyacrylamide gel electrophoresis (PAGE) separation of digested polymerase chain reaction (PCR)-amplificates. The extent of light microscopic changes of liver architecture were studied on haematoxylin, eosin (H. E.) stains. In addition, the extent and the distribution of iron deposition was graded on Prussian blue-stained sections and hepatic iron was quantified by atom absorption spectroscopy. Serum ferritin concentration and the transferrin saturation index were measured using routine laboratory methods. Results: Patients without underlying liver disease (n = 15): Hepatic inflammation was seen in only 8% but fibrosis was found in 36% of compound heterozygous patients. Eighty six percent of those patients had stainable iron predominantly found in Rappaport's zone 1 and 2, but all had a liver iron-index < 1.9. Transferrin saturation was found elevated in 36% of compound heterozygous patients. Patients with liver fibrosis showed significantly higher ferritin levels than patients without liver fibrosis (1110 ng/mL versus 307 ng/mL, p < 0.05). Patients with underlying disease (n = 10): In compound heterozygous patients, 77% had hepatic inflammation and 88% fibrosis. Stainable iron (44%) was less frequently found than in patients without underlying liver disease. Hepatic iron-index in patients with underlying liver disease was always below 1.17; transferrin saturation was elevated in only 22% of the compound heterozygous patients. Histologic hepatic iron-index was significantly lower in patients with underlying disease (median 0.047) as compared to patients without underlying liver disease (median 0.274, P < 0.05). Conclusions: The underlying liver disease determines the extent of hepatic pathology seen in livers of compound heterozygous patients. However, considerable histologic fibrosis can also be found in compound heterozygous patients without underlying liver disease. [source] Raised serum ferritin predicts non-response to interferon and ribavirin treatment in patients with chronic hepatitis C infectionLIVER INTERNATIONAL, Issue 3 2002S Distante Abstract: Background/Aim: Previous studies have indicated that response to interferon therapy is inversely proportional to the amount of body iron stores. We have studied the relationship between serum ferritin, transferrin saturation, liver iron, presence of HFE-C282Y gene mutation and response to treatment in patients with chronic hepatitis C infection. Methods: Two hundred and fifty-six naive, HCV-RNA positive patients (60% males, median age 38 years, range 21,70) were treated with interferon and ribavirin for 6 months. Iron indices and the presence of the C282Y mutation were measured. In 242 (94%) patients iron deposition were determined by Perls staining method. Patients with negative HCV-RNA at 6 months after the end of treatment were defined as sustained viral responders. Results: Non-responders (n = 127) had significantly higher median s-ferritin values compared with sustained viral responders (130 µg/L vs. 75 µg/L P < 0.001). There was no difference in transferrin saturation among the two response groups. Only 23% (4/7) of patients with Perls grade 1 in liver biopsies responded to treatment vs. 54% (122/225) patients without iron deposition (P = 0.02), however, 10/13-non-responders had HCV genotype one. Two patients (0.8%) were homozygous for the C282Y mutation, 36 patients were heterozygous (14%). Among mutation carriers 26/38 achieved sustained response compared with 102/216 non-carriers (68% vs. 48%, P = 0.02). In a multivariate analysis s-ferritin (P = 0.030) and C282Y carrier status (P = 0.012) remained independent predict of sustained response. Conclusions: Raised s-ferritin values predicate non-response to interferon-ribavirin therapy in hepatitis C patients. Response rate in C282Y mutation carriers seems greater than in non-carriers. [source] Indian-subcontinent NBIA: Unusual phenotypes, novel PANK2 mutations, and undetermined genetic forms ,MOVEMENT DISORDERS, Issue 10 2010Annu Aggarwal MD Abstract Neurodegeneration with brain iron accumulation (NBIA) is etiologically, clinically, and by imaging a heterogeneous group including NBIA types 1 [pantothenate kinase-associated neurodegeneration (PKAN)] and 2 (PLA2G6 -associated neurodegeneration), neuroferritinopathy, and aceruloplasminaemia. Data on genetically defined Indian-subcontinent NBIA cases are limited. We report 6 patients from the Indian-subcontinent with a movement disorder and MRI basal ganglia iron deposition, compatible with diagnosis of an NBIA syndrome. All patients were screened for abnormalities in serum ceruloplasmin and ferritin levels and mutations in NBIA-associated genes [pantothenate kinase 2 (PANK2), PLA2G6 and ferritin light chain (exon 4)]. We present clinical, imaging and genetic data correlating phenotype,genotype relations. Four patients carried PANK2 mutations, two of these were novel. The clinical phenotype was mainly dystonic with generalized dystonia and marked orobulbar features in the 4 adolescent-onset cases. One of the four had a late-onset (age 37) unilateral jerky postural tremor. His mutation, c.1379C>T, appears associated with a milder phenotype. Interestingly, he developed the eye-of-the-tiger sign only 10 years after onset. Two of the six presented with adult-onset levodopa (L -dopa)-responsive asymmetric re-emergent rest tremor, developing L -dopa-induced dyskinesias, and good benefit to deep brain stimulation (in one), thus resembling Parkinson's disease (PD). Both had an eye-of-the-tiger sign on MRI but were negative for known NBIA-associated genes, suggesting the existence of further genetic or sporadic forms of NBIA syndromes. In conclusion, genetically determined NBIA cases from the Indian subcontinent suggest presence of unusual phenotypes of PANK2 and novel mutations. The phenotype of NBIA of unknown cause includes a PD-like presentation. © 2010 Movement Disorder Society [source] Renal tubular function in children with ,-thalassemia minorNEPHROLOGY, Issue 5 2005SÜLEYMAN KALMAN SUMMARY: Background: , -thalassemia minor is a common heterozygous haemoglobinopathy that is characterized by both microcytosis and hypochromia. It requires no treatment. It has been postulated that low-grade haemolysis, tubular iron deposition and toxins derived from erythrocytes might cause renal tubular damage in adult patients with , -thalassemia minor. Our aim was to investigate the renal tubular functions in children with ,-thalassemia minor and to determine its possible harmful effects. Methods: The study was conducted on 32 children (14 female and 18 male) at the age of 5.8 ± 3.1 years (range 2,14 years) with , -thalassemia minor. The patients were classified as anaemic (haemoglobin (Hb) , 11 g/dL) (Group 1, n = 14) and non-anaemic (Hb > 11 g/dL) (Group 2, n = 18). A control group was formed with 18 healthy children whose ages and sexes match those in other groups (Group 3, n = 18). Fractional excretion of sodium (FENa, %), fractional excretion of magnesium (FEMg, %), fractional excretion of uric acid (FEUA, %) and tubular phosphorus reabsorption (TPR,%) were calculated with standard formulas. Urinary calcium excretion (mg/kg per 24 h), zinc (Zn) (µg/dL), glucosuria (mg/dL), , -2 microglobulin (mg/dL) and N -acetyl- ,,D-glycosaminidase (NAG, U/mmol creatinine) levels were measured through biochemical methods. Results: There was no statistically significant difference among the three groups in terms of the results of FENa (%), FEMg (%), FEUA (%), TPR (%), calciuria (mg/kg per 24 h), NAG, urine Zn, proteinuria, glucosuria or urine , - 2 microglobulin levels (P > 0.05). Conclusion: On the contrary of children with , -thalassemia major, renal tubular dysfunction has not been determined in children with , -thalassemia minor in the present study. [source] Standardized T2* map of normal human heart in vivo to correct T2* segmental artefactsNMR IN BIOMEDICINE, Issue 6 2007Vincenzo Positano Abstract A segmental, multislice, multi-echo T2* MRI approach could be useful in heart iron-overloaded patients to account for heterogeneous iron distribution, demonstrated by histological studies. However, segmental T2* assessment in heart can be affected by the presence of geometrical and susceptibility artefacts, which can act on different segments in different ways. The aim of this study was to assess T2* value distribution in the left ventricle and to develop a correction procedure to compensate for artefactual variations in segmental analysis. MRI was performed in four groups of 22 subjects each: healthy subjects (I), controls (II) (thalassemia intermedia patients without iron overload), thalassemia major patients with mild (III) and heavy (IV) iron overload. Three short-axis views (basal, median, and apical) of the left ventricle were obtained and analyzed using custom-written, previously validated software. The myocardium was automatically segmented into a 16-segment standardized heart model, and the mean T2* value for each segment was calculated. Punctual distribution of T2* over the myocardium was assessed, and T2* inhomogeneity maps for the three slices were obtained. In group I, no significant variation in the mean T2* among slices was found. T2* showed a characteristic circumferential variation in all three slices. The effect of susceptibility differences induced by cardiac veins was evident, together with low-scale variations induced by geometrical artefacts. Using the mean segmental deviations as correction factors, an artefact correction map was developed and used to normalize segmental data. The correction procedure was validated on group II. Group IV showed no significant presence of segmental artefacts, confirming the hypothesis that susceptibility artefacts are additive in nature and become negligible for high levels of iron overload. Group III showed a greater variability with respect to normal subjects. The correction map failed to compensate for these variations if both additive and percentage-based corrections were applied. This may reinforce the hypothesis that true inhomogeneity in iron deposition exists. Copyright © 2007 John Wiley & Sons, Ltd. [source] Magnetic resonance evaluation of hepatic and myocardial iron deposition in transfusion-independent thalassemia intermedia compared to regularly transfused thalassemia major patients,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2010Ali T. Taher No abstract is available for this article. [source] Patterns of hepatic iron distribution in patients with chronically transfused thalassemia and sickle cell disease,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2009Nilesh R. Ghugre Patients with sickle cell disease (SCD) appear to be at lower risk of endocrinopathies and cardiac dysfunction than those with thalassemia major (TM). Circulating redox active iron is lower in these patients, possibly due to increased systemic inflammation and circulating cytokines. Hepcidin synthesis is upregulated during chronic inflammation, reducing intestinal iron absorption and promoting retention of iron in the reticuloendothelial cells. Hence, we hypothesized that livers of patients with SCD would exhibit greater iron deposition in sinusoidal spaces relative to hepatocytes and less in portal tracts when compared to patients with TM. To test this hypothesis, iron scoring analysis was performed on 70 clinically indicated liver biopsy specimens from children and young adults with the two syndromes. Sinusoidal scores were lower in around 1 of 4 patients with TM but the relative iron loading in hepatocytes, and portal tracts was identical in both diseases. Sinusoidal iron burdens saturated at low hepatic iron concentration (HIC) while hepatocyte and portal iron depots increased proportionally to HIC. Liver fibrosis was increased in patients with TM regardless of their chronic hepatitis status. Overall, liver iron distribution was relatively insensitive to differences in disease type and to the presence or absence of hepatitis. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Mechanisms of iron loading and toxicityAMERICAN JOURNAL OF HEMATOLOGY, Issue S12 2007Gregory J. Anderson Normal iron homeostasis is a finely balanced system that reflects iron absorption, loss and utilization. The body has no mechanism for the active excretion of iron, so body iron levels are controlled at the point of absorption in the small intestine. Disturbances in this equilibrium, such as those leading to enhanced absorption, can have significant clinical consequences. Continued excessive iron uptake is followed by iron deposition in various tissues, ultimately leading to tissue damage, and possibly end-organ failure. In this review, current concepts in normal iron homeostasis, and iron loading are explained. The clinical consequences as well as the differences between primary and secondary iron loading are also reviewed, and some future research priorities are discussed. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Hematologic iron analyte values as an indicator of hepatic hemosiderosis in callitrichidaeAMERICAN JOURNAL OF PRIMATOLOGY, Issue 7 2008Kristine M. Smith Abstract Hepatic hemosiderosis is one of the most common postmortem findings in captive callitrichid species. Noninvasive evaluation of hematologic iron analytes has been used to diagnose hepatic iron storage disease in humans, lemurs, and bats. This study evaluated the relationship between hematologic iron analyte values (iron, ferritin, total iron binding capacity, and percent transferrin saturation) and hepatic hemosiderosis in callitrichids at the Wildlife Conservation Society's Central Park and Bronx Zoos. Results revealed that both ferritin and percent transferrin saturation levels had strong positive correlations with hepatic iron concentration (P<0.001, r=0.77, n=20; P<0.001, r=0.85, n=10, respectively). Serum iron levels positively correlated with hepatic iron concentration (P=0.06, r=0.56, n=11), but this finding was not significant. Serum total iron binding capacity did not significantly correlate with hepatic iron concentration (P=0.47, r=0.25, n=10). Both ferritin and hepatic iron concentration positively correlated with severity of hepatic iron deposition on histology (P<0.05, r=0.49, n=21; P<0.001, r=0.67, n=21, respectively). This study suggests that ferritin, serum iron concentration, and percent transferrin saturation are convenient, noninvasive, antemortem methods for assessing severity of hemosiderosis in callitrichids. Am. J. Primatol. 70:629,633, 2008. © 2008 Wiley-Liss, Inc. [source] Effect of coenzyme Q10 as an antioxidant in ,-thalassemia/Hb E patientsBIOFACTORS, Issue 1-4 2005Ruchaneekorn W. Kalpravidh Abstract Thalassemia is a group of genetic disorders resulting from different mutations in the globin gene complex and leading to an imbalance in globin synthesis. Unmatched globin chains are less stable and susceptible to oxidation. Patients with ,-thalassemia/HbE are prone to increased oxidative stress as indicated by increased lipid peroxidation product, malondialdehyde (MDA), partly because of the presence of iron in the form of heme and hemichromes released from excess globin chains and excess iron deposition in various tissues. The level of antioxidant such as glutathione is markedly decreased while activities of antioxidant enzymes including superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) are increased. We have recently found that the levels of coenzyme Q10 (CoQ10) are also very low in thalassemia. We therefore evaluated the oxidative stress and the antioxidants in these patients before and after supplementation with 100 mg CoQ10 daily for 6 months. The results showed that the plasma level of CoQ10 significantly increased and the oxidative stress decreased as the level of MDA declined. The administration of CoQ10 led to significant improvement of biochemical parameters of antioxidant enzymes. The antioxidant supplementation will be beneficial for thalassemia patients as adjunct therapy to increase their quality of life. [source] Noninvasive assessment of liver fibrosis in thalassaemia major patients by transient elastography (TE) , lack of interference by iron depositionBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2010Vito Di Marco Summary The correlation between liver stiffness, measured by transient elastography, liver fibrosis, using the histological METAVIR score, and iron overload, measured by atomic absorption spectrometry was evaluated in 56 homozygous-,-thalassaemics. Liver stiffness increased proportionally to liver fibrosis staging (r = 0·70; P > 0·001) independently of liver iron concentration (r = 0·01; P = 0·932). The area under the receiver-operating characteristic curve for prediction of cirrhosis was 0·997 (95% confidence interval [CI]: 0·925,1·000) with cut-off of 13 kPa with 100% sensitivity (95% CI: 69·0,100·0) and 95% specificity (95% CI: 84·2,99·3). Transient elastography is a reliable non-invasive tool for diagnosing advanced liver fibrosis in homozygous-,-thalassaemics, regardless of the degree of iron overload. [source] Hepatic and cardiac iron overload among patients with end-stage liver disease referred for liver transplantationCLINICAL TRANSPLANTATION, Issue 5 2010Avital Y. O'Glasser O'Glasser AY, Scott DL, Corless CL, Zaman A, Sasaki A, Gopal DV, Rayhill SC, Orloff SL, Ham JM, Rabkin JM, Flora K, Davies CH, Broberg CS, Schwartz JM. Hepatic and cardiac iron overload among patients with end-stage liver disease referred for liver transplantation. Clin Transplant 2009 DOI: 10.1111/j.1399-0012.2009.01136.x. © 2009 John Wiley & Sons A/S. Abstract:,Background:, Iron overload is associated with fatal cardiovascular events following liver transplantation. Myocardial iron deposits were observed post-mortem in patients who died of cardiac events after transplantation at our institution. This observation prompted testing to exclude cardiac iron in subsequent transplant candidates. Aims:, To assess the results of testing for iron overload in liver transplant candidates at our institution. Methods:, Ferritin, TIBC, and serum iron were measured in cirrhotics referred for transplantation. Patients with transferrin saturation ,50% and ferritin ,250 ng/mL underwent liver biopsy graded for iron. Patients with 3,4+ hepatic iron deposits underwent HFE mutation analysis and endomyocardial biopsy with iron staining. Results:, Eight hundred and fifty-six patients were evaluated for liver transplantation between January 1997 and March 2005. Two hundred and eighty-seven patients (34%) had transferrin saturation ,50% and ferritin ,250 ng/mL. Patients with markers of iron overload had more advanced liver disease than those with normal iron indices. One hundred and fifty-three patients underwent liver biopsy. Twenty-six patients (17%) had 3,4+ hepatic iron staining. One patient was a C282Y heterozygote. Endomyocardial biopsy was performed in 14 patients of whom nine had cardiac iron deposition. Conclusions:, Non-HFE-related cardiac iron overload can occur in advanced liver disease We therefore recommend screening for cardiac iron prior to liver transplantation. [source] | |||||||||||||