The Experts below are selected from a list of 66 Experts worldwide ranked by ideXlab platform
Arthur M Magun - One of the best experts on this subject based on the ideXlab platform.
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Iron-rich foci in chronic viral hepatitis
Human pathology, 1998Co-Authors: Jay H. Lefkowitch, Herman T Yee, Joseph Sweeting, Peter Hr Green, Arthur M MagunAbstract:Stainable iron in the Liver (Hemosiderosis) is most commonly seen in individuals with homozygous genetic hemochromatosis, prior transfusion, hemolysis, porphyria cutanea tarda, and chronic alcohol-induced Liver disease. In chronic viral hepatitis, however, significant hepatocellular Hemosiderosis is uncommon. This report describes unusual foci of hepatocellular Hemosiderosis ("iron-rich foci" or IRF) in Liver biopsy specimens from three patients with chronic hepatitis with or without cirrhosis (two hepatitis C-related, one hepatitis B-related). IRF present within the lobular parenchyma or cirrhotic nodules contrasted sharply with the immediately adjacent hemosiderin-negative Liver tissue. Serum iron indices were abnormal in all three patients, but homozygous hemochromatosis was ruled out based on the hepatic iron concentration and hepatic iron index for each case. These cases highlight the potential for irregular iron storage in chronic viral Liver disease and possible confusion with genetic hemochromatosis. The possible pathogenesis of IRF and the relationship of iron storage to the outcome of interferon therapy in chronic viral hepatitis are discussed.
Jay H. Lefkowitch - One of the best experts on this subject based on the ideXlab platform.
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Iron-rich foci in chronic viral hepatitis
Human pathology, 1998Co-Authors: Jay H. Lefkowitch, Herman T Yee, Joseph Sweeting, Peter Hr Green, Arthur M MagunAbstract:Stainable iron in the Liver (Hemosiderosis) is most commonly seen in individuals with homozygous genetic hemochromatosis, prior transfusion, hemolysis, porphyria cutanea tarda, and chronic alcohol-induced Liver disease. In chronic viral hepatitis, however, significant hepatocellular Hemosiderosis is uncommon. This report describes unusual foci of hepatocellular Hemosiderosis ("iron-rich foci" or IRF) in Liver biopsy specimens from three patients with chronic hepatitis with or without cirrhosis (two hepatitis C-related, one hepatitis B-related). IRF present within the lobular parenchyma or cirrhotic nodules contrasted sharply with the immediately adjacent hemosiderin-negative Liver tissue. Serum iron indices were abnormal in all three patients, but homozygous hemochromatosis was ruled out based on the hepatic iron concentration and hepatic iron index for each case. These cases highlight the potential for irregular iron storage in chronic viral Liver disease and possible confusion with genetic hemochromatosis. The possible pathogenesis of IRF and the relationship of iron storage to the outcome of interferon therapy in chronic viral hepatitis are discussed.
Vineta Fellman - One of the best experts on this subject based on the ideXlab platform.
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The GRACILE syndrome, a neonatal lethal metabolic disorder with iron overload.
Blood cells molecules & diseases, 2002Co-Authors: Vineta FellmanAbstract:GRACILE syndrome (Fellman syndrome, MIM 603358), an autosomal recessive metabolic disorder of the Finnish disease heritage, has been diagnosed in 25 infants of 18 families. The incidence is at least 1/47,000 in Finland. The main findings are fetal growth retardation, Fanconi type aminoaciduria, cholestasis, iron overload (Liver Hemosiderosis, hyperferritinemia, hypotransferrinemia, increased transferrin iron saturation, and free plasma iron), profound lactic acidosis, and early death. The pathophysiology of the metabolic disturbance is unsolved. No significant deficiency of complex III activity of respiratory chain has been found, although we recently showed that the underlying genetic cause is a missense mutation (S78G) in the BCS1L gene and other mutations in that gene have been associated with complex III deficiency. BCS1L encodes a mitochondrial protein, acting as a chaperone in the assembly of complex III. Iron accumulation in Liver, a typical feature being less abundant with increasing age, might be a primary abnormality or a secondary phenomenon due to Liver dysfunction. In order to decrease the iron overload, three infants have been repeatedly treated with apotransferrin followed by exchange transfusion. Improvement in iron biochemistry occurred, but no clear beneficial effect on the clinical condition was found. Further studies will elucidate the role of iron in the pathophysiology of the disease.
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Assignment of the locus for a new lethal neonatal metabolic syndrome to 2q33-37.
American journal of human genetics, 1998Co-Authors: Ilona Visapää, Vineta Fellman, Teppo Varilo, Aarno Palotie, Kari O. Raivio, Leena PeltonenAbstract:A new neonatal syndrome characterized by intrauterine growth retardation, lactic acidosis, aminoaciduria, Liver Hemosiderosis, and early death was recently described. The pathogenesis of this disease is unknown. The mode of inheritance is autosomal recessive, and so far only 17 cases have been reported in 12 Finnish families. Here we report the assignment of the locus for this new disease to a restricted region on chromosome 2q33-37. We mapped the disease locus in a family material insufficient for traditional linkage analysis by using linkage disequilibrium, a possibility available in genetic isolates such as Finland. The primary screening of the genome was performed with samples from nine affected individuals in five families. In the next step, conventional linkage analysis was performed in eight families, with a total of 12 affected infants, and finally the locus assignment was proved by demonstrating linkage disequilibrium to the regional markers in 20 disease chromosomes. Linkage analysis restricted the disease locus to a 3-cM region between markers D2S164 and D2S2359, and linkage disequilibrium with the ancestral haplotype restricted the disease locus further to the immediate vicinity of marker D2S2250.
Dimitrios Christoulas - One of the best experts on this subject based on the ideXlab platform.
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Combination therapy of deferasirox and deferoxamine shows significant improvements in markers of iron overload in a patient with β-thalassemia major and severe iron burden
Transfusion, 2013Co-Authors: Ersi Voskaridou, Veroniki Komninaka, Antonis Karavas, Evangelos Terpos, Vasilis Akianidis, Dimitrios ChristoulasAbstract:BACKGROUND: Iron overload is a common complication of patients with b-thalassemia major (TM). Despite the availability of three iron chelators, deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX), some patients fail to respond adequately to monotherapy with any of them. We report a case of TM who had refractory severe iron overload and was successfully and safely chelated with the combination of DFX with DFO. CASE REPORT: A 40-year-old male with b-TM, who had been regularly transfused from the age of 2, had been administered in the past iron chelation with DFO, DFP, and DFX monotherapy, without major improvement on his iron overload status. Liver and cardiac magnetic resonance imaging (MRI) revealed severe iron overload, while serum ferritin was persistently greater than 2500 mg/L. After the patient gave informed consent, he was administered combination therapy of DFX at 30 mg/kg/day for 7 days per week and DFO at 2500 mg/day for 4 days every week and routinely followed up for compliance. RESULTS: Eighteen months later, serum ferritin was reduced to 680 mg/L, while both Liver and cardiac MRI T2* values improved, reflecting lower iron overload. The combination regimen was well tolerated and no adverse events were documented. CONCLUSION: This is the first official report of simultaneous daily administration of the two iron chelators DFX and DFO that demonstrates the beneficial effect of the combination on heart and Liver Hemosiderosis. If our observation is confirmed in more patients, this combination could constitute a useful option in tailoring individual chelation therapy for b-TM patients with iron overload. I ron overload is a common complication of patients with b-thalassemia major (b-TM) mainly resulting from frequent blood transfusions. Without adequate iron chelation therapy, the majority of b-TM patients will eventually accumulate potentially fatal iron levels leading to cardiac disease, Liver disease (cirrhosis, hepatocellular carcinoma) and endocrine abnormalities. Deferoxamine (DFO) has been the standard of care for more than 40 years doubling the average life span of patients, although the administration through subcutaneous infusions negatively affects patients’ compliance. 1 The available oral iron chelators deferiprone (DFP) and deferasirox (DFX) have shown to be effective in reducing iron burden, simultaneously improving compliance and patients’ quality of life. 2,3 The combination of DFP with DFO has been used to increase the efficacy and induce negative iron balance in some patients with severe iron overload. 4
Fritz Schick - One of the best experts on this subject based on the ideXlab platform.
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Magnetic field distribution in the presence of paramagnetic plates in magnetic resonance imaging: a combined numerical and experimental study.
Medical physics, 2008Co-Authors: Philipp Mertens, Juergen Machann, Bernd Mueller-bierl, Guenter Steidle, Matthias E. Bellemann, Fritz SchickAbstract:The amount and geometric distribution of paramagnetic components in tissue is considered as the basis of T 2 * -weighted magnetic resonance imaging(MRI). Such techniques are routinely applied for assessment of iron in parenchymal organs such as the Liver (Hemosiderosis). Furthermore, susceptibility sensitive MRI is discussed as an alternative method to x-ray techniques for quantitative assessment of paramagnetic spongy bone components in patients with osteoporosis. The presented work is dedicated to systematically examining the possible influences of macroscopic arrangements of paramagnetic plates on the magnetic field. In a theoretical approach magnetic field distribution was simulated applying decomposition of the plates in single dipoles. Plate size and distances between parallel plates, as well as plate orientation with respect to the static field, were varied for these numerical simulations. Experiments on corresponding plate arrangements were carried out on a 3 T whole body MR scanner using the field-sensitive MR sequence technique for B 0 field mapping. Further examinations were carried out on a bone preparation of the femur, where T 2 * maps were measured and analyzed on a pixel-by-pixel basis at two orientations with respect to the static field. A series of experiments were performed using isotropic and anisotropic volume elements in three-dimensional gradient echo sequences. Resulting magnetic field distributions in the experimentally recorded B 0 field maps were in good agreement with the numerical simulations. Field distortions dominated in areas close to the plates and especially near the edges. Those areas showed strong local field gradients, leading to pronounced signal dephasing effects. The examination of the bone preparations revealed different T 2 * values for identical regions in the bone when the orientation of the bone or the pixel geometry was changed with respect to the magnetic field. Those effects amounted to nearly 70% ( 22.9 ms versus 13.6 ms in a region of interest in the femur) for 90° rotation of the femur in the magnetic fields. The orientation of anisotropic picture elements with constant size also showed a strong influence on the derived T 2 * value (up to 80%, increasing with anisotropy of picture elements).