Home About us Contact
|
Home About us Contact | ||
|
|
||
Ferritin Levels (ferritin + level)
Kinds of Ferritin Levels Selected AbstractsHyperferritinemia and iron overload in type 1 Gaucher disease,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2010Philip Stein Hyperferritinemia occurs in Gaucher disease but its clinical spectrum or its association with systemic iron overload and HFE mutations are not known. In 114 patients with Type 1 Gaucher disease, we determined serum ferritin, transferrin saturation and HFE genotype. The results were correlated with the extent of hepatosplenomegaly, overall Gaucher disease severity score index, and response to enzyme replacement therapy. In a subset of patients with radiological and/or laboratory evidence of systemic iron overload, liver biopsy was performed. There was a mean 3.7-fold elevation of serum ferritin over the upper limit of normal (ULN). Prior splenectomy was associated with most severe hyperferritinemia compared to patients with intact spleen (6.53 × ULN vs. 2.69 × ULN, P = 0.003). HFE genotyping revealed two patients homozygous for H63D mutation and 30% of patients heterozygote carriers of H63D mutation; no patients harbored C282Y mutation; there was no correlation of ferritin with HFE genotype. Ferritin level correlated with liver volume (Pearson correlation coefficient = 0.254, P = 0.035) and it was negatively correlated with hemoglobin (r = ,0.315, P = 0.004); there was no relationship with other indicators of Gaucher disease activity. Enzyme replacement therapy (ERT) resulted in amelioration of hyperferritinemia: 707 ± 898 ng/ml vs. 301 ± 310 ng/ml (P = 0.001), transferrin saturation remained normal. Three patients were suspected of clinical iron overload, confirmed on liver biopsy. Iron accumulation was variably noted in hepatocytes and Kupffer cells. There is a high prevalence of hyperferritinemia in Type 1 Gaucher disease that is associated with indicators of disease severity, reversed by ERT and is not related to HFE mutations. Am. J. Hematol. 2010. © 2010 Wiley-Liss, Inc. [source] INTRAVENOUS IRON IN CHRONIC KIDNEY DISEASE: HAEMOGLOBIN CHANGE SHORTLY AFTER TREATMENT OF PATIENTS NEITHER ON DIALYSIS NOR ON ERYTHROPOIETINJOURNAL OF RENAL CARE, Issue 3 2008Senyo Tagboto SUMMARY Anaemia is a common in chronic kidney disease. Although erythropoietin and iron supplementation are established treatments, knowledge on the use of IV iron alone in patients not on dialysis or erythropoietin is incomplete. The responses of 82 patients referred to the renal anaemia service with haemoglobin of 11.5 g/dl or less were assessed 1 week after completing four once weekly doses of 200 mg of venofer. No patients were on dialysis or erythropoietin. The haemoglobin rise 1 week after treatment was 0.53 g/dl. Ferritin levels improved from 110.8 to 410.2 ng/l and transferrin saturation from 17.7 to 27.3%. Ferritin levels remained below our target range (200,500 ng/l) in 7.7% while 25.6% had levels above this. Ferritin levels remained less than 800 ng/l in nearly all patients. Intravenous iron is cost effective and should be considered for use in patients with renal anaemia. Patients with CKD stage 5 appeared to respond less well. [source] Serum thioredoxin elucidates the significance of serum ferritin as a marker of oxidative stress in chronic liver diseasesLIVER INTERNATIONAL, Issue 5 2001Yoshio Sumida Abstract:Background/Aims: Serum thioredoxin (TRX) levels have recently been established as an indicator of oxidative stress in various diseases. The aim of the present study was to clarify the clinical significance of serum ferritin in chronic liver diseases. Methods: Levels of ferritin, transferrin saturation (TS), aspartate aminotransferase (AST), and TRX were measured in the sera of patients with chronic hepatitis C (CH-C, n=92), chronic hepatitis B (CH-B, n=28), nonalcoholic fatty liver (FL, n=31), or alcoholic liver diseases (ALD, n=17). Serum TRX levels were evaluated with a recently established sandwich enzyme-linked immunosorbent assay kit. Results: Serum TRX levels were significantly higher in CH-C, FL, and ALD than in healthy volunteers. A larger proportion of patients with CH-C, FL, and ALD had elevated levels of serum ferritin than CH-B. Serum ferritin levels were positively correlated with levels of TS, AST, and TRX in CH-C, but were merely correlated with TS values in CH-B. Ferritin levels were also well correlated with AST and TRX, but not with TS in FL and ALD. Conclusion: Oxidative stress, which was evaluated by measuring serum TRX, in addition to storage iron and hepatocyte damage is a cause of increasing serum ferritin levels in chronic liver diseases. An elevated serum ferritin level, which was correlated with TS, indicates that iron-induced oxidative stress contributes to CH-C. Elevated ferritin levels in FL and ALD may be mostly due to iron-unrelated stresses. [source] Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosisPEDIATRIC BLOOD & CANCER, Issue 6 2008Carl E. Allen MD Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a potentially lethal condition characterized by a pathologic inflammation. The diagnostic criteria for HLH include fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, abnormal natural killer cell (NK cell) functional assay, elevated soluble IL-2R, level, and elevated ferritin level (>500 µg/L). Institution of timely therapy in these critically ill patients may be delayed by difficulties establishing the diagnosis. NK cell functional assay and soluble IL-2R, level may require send-out to a specialized lab. However, ferritin level is available on a same-day basis at most institutions. In this study, we examined the utility of quantitative ferritin levels in diagnosing HLH. Procedure All patients with ferritin values >500 µg/L obtained at Texas Children's Hospital between January 10, 2003 and January 10, 2005 were identified. Patient charts were reviewed for ferritin levels and hospital course. Results During the study interval, 330 patients had ferritin levels >500 µg/L. Ten of the 330 patients were diagnosed with HLH. A ferritin level over 10,000 µg/L was 90% sensitive and 96% specific for HLH. Another diagnostic category with significantly elevated ferritin level was illness of unknown cause (n,=,10), and only two of these patients were fully evaluated for HLH. Conclusions Ferritin levels above 10,000 µg/L appear to be specific and sensitive for HLH. In patients without a significant medical history and a new onset of febrile illness with highly elevated ferritin levels, the diagnosis of HLH should be evaluated. Pediatr Blood Cancer 2008;50:1227,1235. © 2007 Wiley-Liss, Inc. [source] The long-term impact of ferritin level on treatment and complications of type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 6 2008L. Jiang Aim:, To investigate if high-serum ferritin has long-term impact on response to treatment and the development of diabetic complications in patients with type 2 diabetes. Research design and methods:, We analysed the record of 90 consecutive type 2 diabetic subjects who had serum ferritin level determined soon after diagnosis of diabetes and who also had long-term follow-up data. Results:, Patients with higher serum ferritin level had slightly worse triglyceride, blood pressure and liver enzyme levels at the end of follow up. However, ferritin level had no impact on the initial or final requirements for diabetic medication and the development of diabetic complications. Conclusions:, Although elevated serum ferritin is a marker of insulin resistance and chronic inflammation, it is not necessarily a bad prognostic indicator that should affect the clinician's approach to management. [source] Iron Status: A Possible Risk Factor for the First Febrile SeizureEPILEPSIA, Issue 7 2002Azhar S. Daoud Summary: ,Purpose: We conducted a controlled study to investigate the relation of iron status and first febrile seizure (FFS). Methods: Measures of iron sufficiency including hemoglobin concentration (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and plasma ferritin (PF) were prospectively measured in 75 children with FFS and compared with 75 controls matched for age and sex with febrile illnesses without convulsions. Results: Mean ferritin level was significantly lower in cases with FFS (29.5 ± 21.3 ,g/L) than in controls (53.3 ± 37.6 ,g/L) with p = 0.0001. The proportion of subjects with a PF level ,30 ,g/L was significantly higher among children with FFS (49 of 75 vs. 24 of 75) than in controls (p = 0.000). Mean levels of HB, MCV, and MCH also were lower among FFS cases, but differences failed to attain statistical significance. A higher proportion of cases with FFS had an HB <110 g/L, MCV <72 fL, and MCH <24 pg than did the controls, but the differences were not statistically significant. There were no statistically significant differences between the cases and the controls in the mean peak temperature on admission, types of underlying illness, or family history of epilepsy and of febrile convulsion. Conclusions: PF level was significantly lower in children with FFS than in the reference group, suggesting a possible role for iron insufficiency in FFS. [source] Combined therapy of silymarin and desferrioxamine in patients with ,-thalassemia major: a randomized double-blind clinical trialFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2009Marjan Gharagozloo Abstract Silymarin, a flavonolignan complex isolated from Silybum marianum, has a strong antioxidant, hepatoprotective, and iron chelating activities. The present study was designed to investigate the therapeutic activity of orally administered silymarin in patients with thalassemia major under conventional iron chelation therapy. A 3-month randomized, double-blind, clinical trial was conducted in 59 ,-thalassemia major patients in two well-matched groups. Patients were randomized to receive a silymarin tablet (140 mg) three times a day plus conventional desferrioxamine therapy. The second group received the same therapy but a placebo tablet instead of silymarin. Clinical laboratory tests were assessed at the beginning and the end of the trial, except for serum ferritin level that was assessed at the middle of the trial as well. Results of this study revealed that the combined therapy was well tolerated and more effective than desferrioxamine in reducing serum ferritin level. Significant improvement in liver alkaline phosphatase and glutathione levels of red blood cells was also observed in silymarin-treated ,-thalassemia patients. However, no significant difference in serum ferritin levels was detected between silymarin and placebo groups after 1.5 and 3 months treatment, probably because of insufficient sample size to detect subtle changes in ferritin levels between groups. This is the first report showing the beneficial effects of silymarin in thalassemia patients and suggests that silymarin in combination with desferrioxamine can be safely and effectively used in the treatment of iron-loaded patients. [source] Chronic telogen effluvium or early androgenetic alopecia?INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2004Rodney Sinclair MBBS A 16-year-old girl presented with a 12-month history of generalized hair shedding from the scalp. The onset of shedding coincided with the development of Hashimoto's thyroiditis and iron deficiency. At the time of initial presentation, the Hashimoto's thyroiditis had been treated with Neo-Mercazole and she was euthyroid. Her iron stores were low, with a ferritin level of 13 µg/L. As she was vegetarian, oral iron replacement therapy was commenced without further investigation. On follow-up 6 months later, her iron stores were normal (ferritin, 36 µg/L), but the hair shedding had continued. On examination, there was a positive hair pull test from both the vertex of the scalp and the occipital scalp. There was mild bitemporal recession, but no widening of the central part, and she appeared to have a full, thick head of hair (Fig. 1). Additional investigations at that time revealed normal thyroid function and negative antinuclear antibody (ANA) and syphilis serology. She was on no medication other than Neo-Mercazole. Serum testosterone, dihydroepiandosterone sulphate (DHEAS) and sex hormone binding globulin (SHBG) were normal. Two 4-mm punch biopsies were taken from the vertex of the scalp; one was sectioned horizontally and the other vertically. The vertical section was unremarkable. On the horizontal section, there were 32 hair follicles in total, 30 of which were terminal hairs and two of which were vellus hairs. One hair was in telogen. The ratio of terminal to vellus hairs was 15 : 1. Figure 1. Initial presentation A diagnosis of chronic telogen effluvium was made. The condition was explained to the patient and she was reassured that chronic telogen effluvium is not a progressive condition and does not lead to baldness. No treatment was recommended. At follow-up 12 months later, the hair loss had obviously progressed and the patient was assessed as having Ludwig Stage 1 androgenetic alopecia with widening of the central part (Fig. 2). Repeat blood tests showed normal iron studies, thyroid function, and hormone parameters. Three 4-mm punch biopsies were taken from the vertex of the scalp and all were sectioned horizontally. The terminal to vellus hair ratios were 1 : 1, 2.6 : 1, and 1.9 : 1. A diagnosis of androgenetic alopecia was made and she was commenced on oral spironolactone, 200 mg/day. Figure 2. Presentation after 12 months [source] ORIGINAL ARTICLE: Pro-hepcidin and iron metabolism parameters in multi-time blood donorsINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2010J. BOINSKA Summary A high number of blood donations may cause iron depletion. The pathophysiology behind this process may involve hepcidin, a recently discovered peptide that acts by inhibiting iron absorption and promoting iron retention in reticuloendothelial macrophages. The aim of this study was to determine serum pro-hepcidin levels and iron metabolism parameters in multi-time blood donors. The study group consisted of 132 multi-time male blood donors and 25 healthy male volunteers (nondonors). Complete blood cell count and iron status including serum iron, ferritin, soluble transferrin receptor (sTfR), total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC), erythropoietin and pro-hepcidin (ELISA) were assessed. In blood donors, ferritin level drops markedly in relation to donation frequency (P < 0.001). In contrast, TIBC and UIBC levels increase progressively corresponding to annual donation frequency. Pro-hepcidin concentration increases significantly with the number of donations per year (P = 0.0290). In blood donors having donated blood with the highest frequency per year, pro-hepcidin levels were positively correlated with haemoglobin (R = 0.31, P < 0.05) and negatively with sTfR (R = ,0.31, P < 0.05). Pro-hepcidin levels increase in relation to blood donation frequency per year. Longitudinal studies focusing on changes in serum hepcidin levels are required to address the question whether hepcidin may contribute to iron metabolism disturbances in multi-times blood donors. [source] Useful parameters for distinguishing nonalcoholic steatohepatitis with mild steatosis from cryptogenic chronic hepatitis in the Japanese populationLIVER INTERNATIONAL, Issue 8 2006Naoki Tanaka Abstract: Background/Aims: As detecting mild steatosis is difficult by abdominal ultrasonography (US), nonalcoholic steatohepatitis (NASH) with mild steatosis may sometimes be confused with cryptogenic chronic hepatitis. We aimed to test this possibility and to isolate factors that may indicate NASH. Methods: First, 53 Japanese patients diagnosed as having cryptogenic chronic hepatitis by laboratory examination and US were enrolled. These patients were histologically divided into NASH and non-NASH groups, and their clinical features were compared. Second, the diagnostic accuracy of predictors of NASH was examined prospectively. Results: Fifteen patients (28%) were histologically diagnosed as having NASH with mild steatosis. Multivariable analysis revealed that body mass index (BMI) and serum ferritin level were independent predictors of NASH. The best cutoff values to detect NASH were assessed by using receiver-operating characteristic curves: BMI>25.2 kg/m2 and serum ferritin level >142 ng/ml. When both markers were concomitantly negative, the negative predictive value to detect NASH was 100%. Conclusions: In cases of mild steatosis, US is not a perfect tool for the accurate diagnosis of NASH. BMI and serum ferritin level are useful discriminators of NASH from cryptogenic chronic hepatitis, and might be helpful markers for diagnosing NASH more accurately in Japanese patients. [source] Insulin resistance/,-cell function and serum ferritin level in non-diabetic patients with hepatitis C virus infectionLIVER INTERNATIONAL, Issue 4 2003Masanori Furutani Abstract Background/Aims: Since impaired glucose tolerance and iron overload are frequently demonstrated in hepatitis C virus (HCV)-related liver diseases, in this study we investigated insulin resistance, pancreatic ,-cell function, i.e., insulin secretion, and serum ferritin levels in patients with HCV infection, especially non-diabetic patients. Methods: Homeostasis model assessments for insulin resistance (HOMA-IR) and ,-cell function (HOMA-,) were performed in 92 HCV-infected patients. Results: The levels of plasma immunoreactive insulin (IRI), HOMA-IR, and HOMA-, were significantly correlated with fasting plasma glucose (FPG) levels. Among the 86 non-diabetics (with an FPG of <126 mg/dl), IRI, HOMA-IR, and HOMA-, were significantly higher in patients with liver cirrhosis than in patients with persistently normal alanine aminotransferase levels. The IRI and HOMA-IR values, but not the HOMA-, values, were correlated with both serum transaminase and ferritin levels in the 65 non-diabetic chronic hepatitis patients. Conclusion: Insulin resistance was connected with impaired glucose tolerance and the severity of liver diseases in non-diabetic patients with HCV infection. Iron overload may be responsible for insulin resistance, or vice versa. Pancreatic ,-cell function was unrelated to the patients' serum ferritin levels. [source] Serum thioredoxin elucidates the significance of serum ferritin as a marker of oxidative stress in chronic liver diseasesLIVER INTERNATIONAL, Issue 5 2001Yoshio Sumida Abstract:Background/Aims: Serum thioredoxin (TRX) levels have recently been established as an indicator of oxidative stress in various diseases. The aim of the present study was to clarify the clinical significance of serum ferritin in chronic liver diseases. Methods: Levels of ferritin, transferrin saturation (TS), aspartate aminotransferase (AST), and TRX were measured in the sera of patients with chronic hepatitis C (CH-C, n=92), chronic hepatitis B (CH-B, n=28), nonalcoholic fatty liver (FL, n=31), or alcoholic liver diseases (ALD, n=17). Serum TRX levels were evaluated with a recently established sandwich enzyme-linked immunosorbent assay kit. Results: Serum TRX levels were significantly higher in CH-C, FL, and ALD than in healthy volunteers. A larger proportion of patients with CH-C, FL, and ALD had elevated levels of serum ferritin than CH-B. Serum ferritin levels were positively correlated with levels of TS, AST, and TRX in CH-C, but were merely correlated with TS values in CH-B. Ferritin levels were also well correlated with AST and TRX, but not with TS in FL and ALD. Conclusion: Oxidative stress, which was evaluated by measuring serum TRX, in addition to storage iron and hepatocyte damage is a cause of increasing serum ferritin levels in chronic liver diseases. An elevated serum ferritin level, which was correlated with TS, indicates that iron-induced oxidative stress contributes to CH-C. Elevated ferritin levels in FL and ALD may be mostly due to iron-unrelated stresses. [source] Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosisPEDIATRIC BLOOD & CANCER, Issue 6 2008Carl E. Allen MD Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a potentially lethal condition characterized by a pathologic inflammation. The diagnostic criteria for HLH include fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, abnormal natural killer cell (NK cell) functional assay, elevated soluble IL-2R, level, and elevated ferritin level (>500 µg/L). Institution of timely therapy in these critically ill patients may be delayed by difficulties establishing the diagnosis. NK cell functional assay and soluble IL-2R, level may require send-out to a specialized lab. However, ferritin level is available on a same-day basis at most institutions. In this study, we examined the utility of quantitative ferritin levels in diagnosing HLH. Procedure All patients with ferritin values >500 µg/L obtained at Texas Children's Hospital between January 10, 2003 and January 10, 2005 were identified. Patient charts were reviewed for ferritin levels and hospital course. Results During the study interval, 330 patients had ferritin levels >500 µg/L. Ten of the 330 patients were diagnosed with HLH. A ferritin level over 10,000 µg/L was 90% sensitive and 96% specific for HLH. Another diagnostic category with significantly elevated ferritin level was illness of unknown cause (n,=,10), and only two of these patients were fully evaluated for HLH. Conclusions Ferritin levels above 10,000 µg/L appear to be specific and sensitive for HLH. In patients without a significant medical history and a new onset of febrile illness with highly elevated ferritin levels, the diagnosis of HLH should be evaluated. Pediatr Blood Cancer 2008;50:1227,1235. © 2007 Wiley-Liss, Inc. [source] Red blood cell transfusion need at diagnosis adversely affects survival in primary myelofibrosis,increased serum ferritin or transfusion load does not,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2009Ayalew Tefferi Serum ferritin level at diagnosis was available in 185 patients with primary myelofibrosis (PMF); twenty-two (12%) patients had serum ferritin >1,000 ng/mL and 32 (17%) were red blood cell (RBC) transfusion-dependent. As expected, RBC transfusion need and increased serum ferritin displayed strong correlation (P < 0.0001); in addition, the latter but not the former correlated with advanced age (P < 0.0001). During median follow-up of 28 months (range 0.5,231), peak serum ferritin levels exceeded 1,000 ng/mL in 41 (22%) patients. On multivariable analysis that included age as a covariate, RBC transfusion need at diagnosis (P < 0.0001), but not increased serum ferritin or transfusion load, predicted shortened survival. The prognostic relevance of RBC transfusion need was independent of the International Prognostic Scoring System and was also illustrated for leukemia-free survival (P = 0.003). In PMF, the presence of a more severe erythropoietic defect, and not iron overload, has additional adverse prognostic value. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Granulocyte function in patients with L-ferritin iron-responsive element (IRE) 39C,T-positive hereditary hyperferritinaemia,cataract syndromeEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2004R. Fritsche-Polanz Abstract Background, Hereditary hyperferritinaemia,cataract syndrome (HHCS) is an autosomal dominant trait associated with mutations in the iron responsive element (IRE) of the ferritin light-chain (L-ferritin) gene. Patients typically show elevated serum ferritin concentrations without iron overload and a bilateral cataract. Hyperferritinaemia can be associated with granulocyte dysfunction in patients with thalassemia beta and in haemodialysis patients. The effect of increased L-ferritin levels on granulocyte function in patients with HHCS is unknown. Material and methods, We examined glucose uptake, oxidative burst, chemotaxis, phagocytosis, apoptosis and intracellular calcium concentrations in polymorphonuclear leucocytes (PMNLs) of five affected members of a family with HHCS and in five healthy individuals matched for age and gender. Results, Mutation testing revealed a 39C,T transition in IRE in all five patients with HHCS. Serum ferritin levels of patients ranged between 907 and 2030 µg L,1, respectively. In comparison with healthy individuals, PMNLs of patients with HHCS showed a significant increase in PMA-mediated stimulation of the oxidative burst, as well as a significantly higher stimulation of glucose uptake but no difference with respect to chemotaxis, phagocytosis, apoptosis and intracellular calcium concentrations. Conclusion, In summary, our study suggests that hyperferritinaemia in patients with IRE 39C,T-positive HHCS is associated with activation of PMNLs but not with disturbance of fundamental PMNL function. [source] Oxidative stress in red blood cells, platelets and polymorphonuclear leukocytes from patients with myelodysplastic syndromeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2007Hussam Ghoti Abstract Low-risk myelodysplastic syndrome (MDS) is characterized by cytopenia, mainly anemia, because of ineffective hematopoiesis. Some of the patients with ineffective erythropoiesis, with or without ring sideroblasts in their bone marrow, develop severe anemia requiring frequent blood transfusions and consequently develop iron overload. Excess free iron in cells catalyses the generation of reactive oxygen species (ROS) that cause cell and tissue damage. Using flow cytometry techniques, we compared the oxidative status of red blood cells (RBC), platelets and neutrophils in 14 MDS patients with those of normal donors. The results show that ROS were higher while reduced glutathione (GSH) was lower in their RBC and platelets compared with normal cells. In neutrophils, no difference was found in ROS, while the GSH levels were lower. A correlation (r = 0.6) was found between serum ferritin levels of the patients and the ROS in their RBC and platelets. The oxidative stress was ameliorated by a short incubation with the iron-chelators, the deferrioxamine and deferiprone or with antioxidants such as N -acetylcysteine, suggesting that MDS patients might benefit from treatment with iron-chelators and antioxidants. [source] H63D homozygotes with hyperferritinaemia: is this genotype, the primary cause of iron overload?EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2007Carles De Diego Abstract Objectives:,Hereditary haemochromatosis is a disease that affects iron metabolism and leads to iron overload. Homozygosity for the H63D mutation is associated with increased transferrin saturation (TS) and ferritin levels. Our objective was to find out if the homozygosity of H63D mutation was the primary cause of iron overload. Patients and methods:,We studied 45 H63D homozygotes (31 males and 14 females) with biochemical iron overload and/or clinical features of haemochromatosis. The simultaneous detection of 18 known HFE, TFR2 and FPN1 mutations and sequencing of the HAMP gene were performed to rule out the possible existence of genetic modifier factors related with iron overload. Results:,Values of biochemical iron overload, measured as percentage TS and serum ferritin concentration (SF), in our H63D homozygotes were significantly higher in patients than in controls: TS 55 ± 15% vs. 35 ± 15% and SF 764 (645,883) ,g/L vs. 115 (108,123) ,g/L for patients and controls, respectively. These H63D homozygotes presented extreme hyperferritinaemia and no additional mutations in HFE, TFR2, FPN1 and HAMP genes were detected. Conclusions:,The lack of additional mutations in our H63D homozygotes suggests that this genotype could be the primary cause of iron overload in these patients. Despite our results, we cannot entirely discount the possibility that one or more genetic modifier factor exists, simply because we were unable to find it, although there was a precedent in the HFE gene. Genetic modifier factors have been described for C282Y mutations in the HFE gene, but at the present time they have never been reported in H63D homozygotes. [source] Reversal of cardiac complications in thalassemia major by long-term intermittent daily intensive iron chelationEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2003H. Miskin Abstract: Objectives: In patients with thalassemia major (TM) who are non-compliant with long-term deferoxamine (DFO) chelation, survival is limited mainly because of cardiac complications of transfusional siderosis. It was recently shown in a small group of TM patients with established cardiac damage that continuous 24-h DFO infusion via an indwelling intravenous (i.v.) catheter is effective in reversing cardiac toxicity. The aim of the present study was to evaluate the results with intermittent daily (8,10 h) i.v. DFO. Patients: Eight TM patients with cardiac complications treated with intensive intermittent DFO were retrospectively evaluated by the mean annual serum ferritin, radionucleated ventriculography and 24-h electrocardiography recordings. Results: The median age at diagnosis of cardiac disease was 17.5 yr (range 14,21), and the median follow-up time was 84 months (range, 36,120). In the majority of patients (seven of eight) high-dose DFO (mean 95 ± 18.3 mg/kg/d) was administered via a central venous line. During follow-up, there was a significant decrease in the mean ferritin levels (5828 ± 2016 ng/mL to 1585 ± 1849 ng/mL, P < 0.001). Both cardiac failure (mean ejection fraction 32 ± 5) and cardiac arrhythmias were resolved in four of five patients. One non-compliant patient died during the follow-up. Following discontinuation of the i.v. therapy, compliance with conventional DFO therapy improved. The complications of this regimen, mainly catheter-related infections and catheter-related thrombosis, were similar to those described earlier. Conclusions: These results with the longest follow-up period in the literature suggest that i.v. high-dose DFO for 8,10 h daily may be as effective as continuous 24-h infusion for the reversal of established cardiac disease in TM. [source] Combined therapy of silymarin and desferrioxamine in patients with ,-thalassemia major: a randomized double-blind clinical trialFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2009Marjan Gharagozloo Abstract Silymarin, a flavonolignan complex isolated from Silybum marianum, has a strong antioxidant, hepatoprotective, and iron chelating activities. The present study was designed to investigate the therapeutic activity of orally administered silymarin in patients with thalassemia major under conventional iron chelation therapy. A 3-month randomized, double-blind, clinical trial was conducted in 59 ,-thalassemia major patients in two well-matched groups. Patients were randomized to receive a silymarin tablet (140 mg) three times a day plus conventional desferrioxamine therapy. The second group received the same therapy but a placebo tablet instead of silymarin. Clinical laboratory tests were assessed at the beginning and the end of the trial, except for serum ferritin level that was assessed at the middle of the trial as well. Results of this study revealed that the combined therapy was well tolerated and more effective than desferrioxamine in reducing serum ferritin level. Significant improvement in liver alkaline phosphatase and glutathione levels of red blood cells was also observed in silymarin-treated ,-thalassemia patients. However, no significant difference in serum ferritin levels was detected between silymarin and placebo groups after 1.5 and 3 months treatment, probably because of insufficient sample size to detect subtle changes in ferritin levels between groups. This is the first report showing the beneficial effects of silymarin in thalassemia patients and suggests that silymarin in combination with desferrioxamine can be safely and effectively used in the treatment of iron-loaded patients. [source] ORIGINAL ARTICLE Clinical haemophilia: Remission of paroxysmal atrial fibrillation with iron reduction in haemophilia AHAEMOPHILIA, Issue 5 2010L. R. ZACHARSKI Summary., Two male first cousins with mild haemophilia A had baseline factor VIII levels of 12,15% and experienced bleeding requiring coagulation factor infusion therapy with trauma and surgical procedures. Both the patients with haemophilia A also had electrocardiographically documented symptomatic paroxysmal atrial fibrillation (PAF) for several years that had become resistant to pharmacological suppression. Radiofrequency ablation was considered in both the cases but deferred considering refusal of consent by the patients to undergo the procedure. Remission of arrhythmias has been reported in patients with iron-overload syndromes. Body iron stores assessed by serum ferritin levels were elevated in both men but neither had the C282Y or H63D genes for haemochromatosis. Calibrated reduction of iron stores by serial phlebotomy, avoiding iron deficiency, was followed by remission of symptomatic PAF in both cases. Iron reduction may be an effective treatment for arrhythmias apart from the classic iron-overload syndromes and deserves further study particularly in patients with bleeding disorders who might be at risk for arrhythmias and other diseases of ageing. [source] Iron-overload and genotypic expression of HFE mutations H63D/C282Y and transferrin receptor Hin6I and BanI polymorphism in German patients with hereditary haemochromatosisINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2000R. Gottschalk Gene variations of HFE, a HLA-class I like molecule, are highly associated with hereditary haemochromatosis (HH). Functional as well as molecular studies of the HFE protein have indicated that the molecule is involved in iron metabolism and that the HFE gene variations observed among HH patients affect its interaction with the transferrin receptor (TfR). In the present study, we have therefore analysed the relationship between the HFE gene variants, C282Y and H63D, and body iron status among 85 German HH patients. In addition, two TfR gene polymorphism, TfR-Hin6I and TfR-BanI, were typed that have been reported to define ethnically distinct haplotypes. As controls we used 251/159 healthy German blood donors. Seventy-eight (92%) patients were C292Y homozygous, the H63D mutation was present in five (6%) patients with none of the patients being H63D homozygous. Serum transferrin, transferrin saturation and liver iron content were determined prior to therapeutic intervention. Among C282Y homozygous patients serum ferritin levels (2294 ± 3174 vs. 463 ± 224 µg L,1, P < 0.0001) and transferrin saturation (86 ± 18% vs. 62 ± 25%, P = 0.048) were elevated significantly compared with C282Y and/or H63D heterozygous patients. In addition, the liver iron content (291 ± 165 vs. 138 ± 95 µmol g,1, P = 0.028) and liver iron index (6.4 ± 2.8 vs. 3.2 ± 2.3, P = 0.019) were increased among C282Y homozygotes compared with C282Y heterozygotes. In contrast, no difference was observed between patients and controls regarding the distribution of TfR- Hin6I and TfR- BanI alleles. These data indicate that the iron intake is higher among C282Y homozygous patients compared with C282Y heterozygous or C282Y/H63D compound heterozygous individuals and supports the functional role of the HFE protein in iron metabolism whereas the TfR gene variants seem to have no influence on iron uptake. [source] Restriction of dietary calories, fat and iron improves non-alcoholic fatty liver diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2007Mika Yamamoto Abstract Background:, The pathogenesis of non-alcoholic steatohepatitis (NASH) is unclear. Recent studies suggested that oxidative stress plays an important role in the mechanism of NASH. Excessive accumulation of iron in the liver causes oxidative stress. The aim of the present study was to evaluate the grade of hepatic iron accumulation and the therapeutic response to restriction of calories, fat and iron in patients with non-alcoholic fatty liver disease (NAFLD). Methods:, Twenty-seven NAFLD patients were enrolled. The patients were categorized into two groups: 17 patients with NASH and 10 with simple steatosis. Twelve NAFLD patients (NASH, n = 9; simple steatosis, n = 3) were given a dietary prescription including restriction of energy, fat and iron. Results:, Positive iron staining was observed in 71% and 50% of patients with NASH and simple steatosis, respectively. The average energy intake, fat energy fraction and iron intake decreased significantly 6 months after the beginning of the diet in all patients. In addition, the levels of serum transaminase and ferritin were significantly decreased. Conclusion:, Dietary restriction of calories, fat and iron improved NAFLD. Reduced serum ferritin levels appear to reduce oxidative stress in the liver. [source] Dietary intakes and nutrient status of vegetarian preschool children from a British national surveyJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 3 2000C.W. Thane Background Dietary intakes and nutrient status were compared in meat-eaters and non-meat-eaters from the National Diet and Nutrition Survey of children aged 1.5,4.5 years. Methods Children (n = 1351) were categorized as ,omnivores' or ,vegetarians', according to whether they consumed meat or meat products during a 4-day dietary record. Blood samples were also obtained for analysis of haematological and biochemical nutrient status. Results Three per cent of children were ,vegetarian'. They consumed higher proportions of milk and milk products, although this was significant only in older children (P = 0.007), owing to high consumption by the high proportion of Asian children. In vegetarians, energy intakes tended to be lower in both age groups. Percentage energy from protein and fat were lower, while that from carbohydrate was higher compared with omnivores. Cholesterol intakes were lower, significantly so for younger children (P < 0.001). Intakes of micronutrients were either higher (vitamins C and E, potassium) or lower (niacin and sodium) in younger vegetarians compared with omnivores. Energy-adjusted intakes of iron and zinc did not differ significantly from those of omnivores, although both intakes were low in many children (6,20% < LRNI), particularly in the younger group. Haematological and biochemical nutrient status indices showed few differences. Serum ferritin was lower in vegetarians, significantly so in younger children (P = 0.002). Antioxidant vitamin (A, C and E) status tended to be higher in vegetarians, while vitamin B12 intakes and status were more than adequate. Apart from poorer vitamin D intake and status in older Asian vegetarians, very few ethnic differences were observed. Conclusions Nutrient intakes and status were generally adequate in preschool children who did not eat meat. Although serum ferritin levels were inferior (particularly in vegetarians under 3 years old), the lower intakes of fat, cholesterol and sodium, and higher antioxidant vitamin intakes and status indices were potentially beneficial. Given a balanced diet, adequate nutrient intakes and status can be maintained without consuming meat. [source] Helicobacter pylori infection detected by 14C-Urea breath test is associated with iron deficiency anemia in pregnant womenJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 6 2008s Mulayim Abstract Aims:, To determine whether there is a relationship between Helicobacter pylori (H. pylori) infection, iron deficiency anemia and thrombocytopenia in pregnant women. Methods:, Hemoglobin and ferritin levels and platelet counts of pregnant women were measured during the third trimester. H. pylori infection was determined using a 14C-urea breath test (14C-UBT) after delivery. Statistical analyses were determined with a Mann,Whitney U -test and the ,2 test. Statistical significance was determined with a P -value less than .05. Results:, Seventy-two of 117 women had positive results on the 14C-UBT. Overall, 27 of 117 pregnant women had anemia (23.1%), and all them were in the H. pylori -positive group; 18 of 27 (66.7%) had iron deficiency anemia. Median hemoglobin levels and neonatal body weights were 12.0 g/dL vs 12.0 g/dL and 3320.0 grams vs 3520.0 grams in the H. pylori -positive and negative groups, respectively. Serum hemoglobin and ferritin levels and neonatal body weight were found to be lower in the anemic group compared with the non-anemic group among H. pylori -infected women (P = 0.0001, P = 0.02, P = 0.008, respectively). There were no statistically significant differences with regard to gestational thrombocytopenia between the H. pylori -positive and H. pylori -negative groups (P = 0.532). Conclusions:, Our study indicates that there is a strong relationship between H. pylori infection and iron deficiency anemia in women with uncomplicated pregnancy. However, an association between H. pylori infection and thrombocytopenia was not found. [source] Influence of Helicobacter pylori infection on iron accumulation in hepatitis CLIVER INTERNATIONAL, Issue 7 2006Yoshio Sumida Abstract: Goal: Iron may play a role in the pathogenesis of chronic hepatitis C. Helicobacter pylori (Hp) infection was recently associated with iron-deficiency anemia. We examined the influence of Hp infection on hepatic iron accumulation in hepatitis C. Methods: Ninety-five hepatitis C virus (HCV)-RNA-positive patients, including 60 chronic hepatitis, 17 cirrhosis and 18 hepatocellular carcinoma as well as 95 age- and sex-matched normal subjects without HCV infection as control, were studied. Liver biopsies were also obtained from 44 HCV-infected patients. Serum Hp antibodies were measured by an enzyme-linked immunosorbent assay and clinical data, including iron parameters and histological findings, were compared between Hp-positive and -negative HCV-infected patients. Results: The percentage of serum Hp antibodies was lower in HCV-infected patients than in controls (52/95 (54.7%) vs. 68/95 (71.6%); P<0.05). HCV-infected patients had higher serum ferritin levels than controls (120 [2.8,1700] vs. 58 [2.2,420] ng/ml; P<0.0001). In HCV-infected patients, the serum ferritin levels (medians and [ranges]) in Hp-positive patients were significantly lower than those of Hp-negative patients (99 [8.5,770] vs. 150 [2.8,1700] ng/ml; P<0.05). The grades of hepatic iron deposit in Hp-positive patients were significantly lower than those in Hp-negative patients (P<0.01). Conclusions: Hp infection may at least partly affect hepatic iron accumulation in HCV-related liver diseases. [source] Insulin resistance/,-cell function and serum ferritin level in non-diabetic patients with hepatitis C virus infectionLIVER INTERNATIONAL, Issue 4 2003Masanori Furutani Abstract Background/Aims: Since impaired glucose tolerance and iron overload are frequently demonstrated in hepatitis C virus (HCV)-related liver diseases, in this study we investigated insulin resistance, pancreatic ,-cell function, i.e., insulin secretion, and serum ferritin levels in patients with HCV infection, especially non-diabetic patients. Methods: Homeostasis model assessments for insulin resistance (HOMA-IR) and ,-cell function (HOMA-,) were performed in 92 HCV-infected patients. Results: The levels of plasma immunoreactive insulin (IRI), HOMA-IR, and HOMA-, were significantly correlated with fasting plasma glucose (FPG) levels. Among the 86 non-diabetics (with an FPG of <126 mg/dl), IRI, HOMA-IR, and HOMA-, were significantly higher in patients with liver cirrhosis than in patients with persistently normal alanine aminotransferase levels. The IRI and HOMA-IR values, but not the HOMA-, values, were correlated with both serum transaminase and ferritin levels in the 65 non-diabetic chronic hepatitis patients. Conclusion: Insulin resistance was connected with impaired glucose tolerance and the severity of liver diseases in non-diabetic patients with HCV infection. Iron overload may be responsible for insulin resistance, or vice versa. Pancreatic ,-cell function was unrelated to the patients' serum ferritin levels. [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] Serum thioredoxin elucidates the significance of serum ferritin as a marker of oxidative stress in chronic liver diseasesLIVER INTERNATIONAL, Issue 5 2001Yoshio Sumida Abstract:Background/Aims: Serum thioredoxin (TRX) levels have recently been established as an indicator of oxidative stress in various diseases. The aim of the present study was to clarify the clinical significance of serum ferritin in chronic liver diseases. Methods: Levels of ferritin, transferrin saturation (TS), aspartate aminotransferase (AST), and TRX were measured in the sera of patients with chronic hepatitis C (CH-C, n=92), chronic hepatitis B (CH-B, n=28), nonalcoholic fatty liver (FL, n=31), or alcoholic liver diseases (ALD, n=17). Serum TRX levels were evaluated with a recently established sandwich enzyme-linked immunosorbent assay kit. Results: Serum TRX levels were significantly higher in CH-C, FL, and ALD than in healthy volunteers. A larger proportion of patients with CH-C, FL, and ALD had elevated levels of serum ferritin than CH-B. Serum ferritin levels were positively correlated with levels of TS, AST, and TRX in CH-C, but were merely correlated with TS values in CH-B. Ferritin levels were also well correlated with AST and TRX, but not with TS in FL and ALD. Conclusion: Oxidative stress, which was evaluated by measuring serum TRX, in addition to storage iron and hepatocyte damage is a cause of increasing serum ferritin levels in chronic liver diseases. An elevated serum ferritin level, which was correlated with TS, indicates that iron-induced oxidative stress contributes to CH-C. Elevated ferritin levels in FL and ALD may be mostly due to iron-unrelated stresses. [source] Neonatal hemochromatosis , medical treatment vs.LIVER TRANSPLANTATION, Issue 11 2005Transplantation: The king's experience The aim of our study was to compare the outcome of medical treatment vs. liver transplantation in infants with neonatal hemochromatosis (NH) referred to King's College Hospital from 1990-2002. We conducted a retrospective review of 19 children from 14 families. Fifteen children presented at birth and 4 during the first week of life. One child was diagnosed by cordocentesis at 30 weeks of gestation. NH recurred in 7 of 9 families with further children. In one family, 2 children from different fathers were affected. All patients had elevated ferritin levels, hypoalbuminemia, and coagulopathy. Liver histology showed parenchymal collapse, diffuse fibrosis, and moderate to severe hepatocyte hemosiderin deposition. Extrahepatic siderosis was demonstrated by magnetic resonance in 2 patients, lip biopsy in 3, and autopsy in 10. Ten patients received a chelation-antioxidant cocktail: 1 survived, 4 died, and 5 required liver transplantation, of whom 2 died. One of the 9 infants who did not receive the cocktail survived with medical support, 3 died, and 5 required transplantation, of whom 3 died. Seven children are alive, 5 after transplantation, at a median follow-up of 5.6 years, with excellent quality of life and no recurrence of the disease. In conclusion, chelation-antioxidant treatment does not appear to modify the prognosis of NH, at least in severe cases. Liver transplantation, with 50% long-term survival, remains the treatment of choice and should be promptly offered to those infants who do not improve with supportive medical treatment. (Liver Transpl 2005;11:1417,1424.) [source] Nutritional status in pregnant adolescents: a systematic review of biochemical markersMATERNAL & CHILD NUTRITION, Issue 2 2007Victoria Hall Moran Abstract Adolescent pregnancy is a major public health challenge for many industrialized countries and is associated with significant medical, nutritional, social and economic risk for mothers and their infants. Despite this, relatively little is known about the nutritional status of this population. The aim of this paper was to conduct a systematic review of the current evidence relating to the biochemical markers of nutritional status of pregnant adolescents living in industrialized countries. Six papers were identified that fulfilled the inclusion criteria, the majority of which were conducted in the United States. The studies were of variable quality and most failed to control for potential confounders which may have strongly influenced the findings. Due to limited research, conclusions cannot be drawn about the zinc and calcium status of pregnant adolescents, and data on folate and vitamin B12 status appeared conflicting. There was some consensus among studies, however, to suggest that indicators of anaemia and iron status were compromised in pregnant adolescents, particularly during the third trimester of pregnancy. Chronological age did not appear to influence nutritional status, although there was some evidence to suggest that increasing gynaecologic age may positively influence plasma ferritin levels. Current research is limited by sampling and measurement bias, and research is urgently required to address these limitations. Further consideration should also be made of the influence of the role of socio-economic support on pregnant adolescents' nutritional status. The achievement of improved nutrition in pregnancy among adolescents requires multidisciplinary collaborations of adolescent healthcare providers, academics, professional organizations, policymakers, industry and service users. Only once this is achieved can adolescent nutrition, and adolescent nutrition in pregnancy, be significantly and sustainably optimized. [source] | |||||||||||||||||||||||||||||||