Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac complications in 110 patients (mean age, 32.5 +/- 11.4 years) with thalassemia intermedia (TI) were studied. Sixty-seven (60.9%) of them had not been transfused or were minimally transfused (group A). The rest had started transfusions after the age of 5 years (mean, 15.1 +/- 10.1 years), initially on demand and later more frequently (group B). Overall mean hemoglobin and ferritin levels were 9.1 +/- 1.1 g/dL and 1657 +/- 1477 ng/mL, respectively. Seventy-six healthy controls were also studied. The investigation included thorough history taking, clinical examination, electrocardiography, chest radiograph, and full resting echocardiography. Of 110 patients, 6 (5.4%) had congestive heart failure (CHF), and 9 (8.1%) had a history of acute pericarditis. Echocardiography showed pericardial thickening, with or without effusion, in 34.5% of the patients. Valvular involvement included leaflet thickening (48.1%), endocardial calcification (20.9%), and left-sided valve regurgitation (aortic, 15.4%; mitral, 47.2%). All patients had normal left ventricular contractility (fractional shortening, 0.43 +/- 0.05), and high cardiac output (CO; 9.34 +/- 2.28 L/min). Pulmonary hypertension (PHT), defined as Doppler peak systolic tricuspid gradient greater than 30 mm Hg, developed in 65 patients (59.1%). PHT correlated positively with age and CO and did not differ significantly between groups. Cardiac catheterization in the 6 patients with CHF revealed severe PHT, increased pulmonary resistance (PVR), and normal capillary wedge pressure. It was concluded that in patients with TI, the heart is primarily affected by PHT, which is the leading cause of CHF. High CO resulting from chronic tissue hypoxia and increased PVR are the main contributing factors. Doppler tricuspid gradient measurement should be considered, in addition to other factors, when determining the value of transfusion therapy for patients with TI. (Blood. 2001;97:3411-3416)
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PMID:Cardiac involvement in thalassemia intermedia: a multicenter study. 1136 31

The aim of this study was to assess the erythropoietic response to hypoxaemia in patients with diffuse idiopathic pulmonary fibrosis (DIPF), and to speculate on the underlying mechanisms. Patients on an established chronic respiratory failure due to DIPF or chronic obstructive pulmonary disease (COPD) were studied. The erythropoietic response to hypoxaemia in both conditions was assessed. We studied 18 patients with DIPF and 29 patients with COPD in respiratory failure in a stable stage, free from acute infection and congestive heart failure. Blood gases, erythrocytic parameters, as well the serum levels of iron, ferritin and erythropoietin were determined. All the DIPF patients studied, apart from two, had normal or subnormal haematocrit values. The patients with COPD had an inconsistant response to hypoxaemia; 12 had normal or subnormal haematocrit values and the remaining 17 were erythraemic. The mean value of erythropoietin (EPO) in both DIPF and COPD patients was significantly higher than normal. In conclusion, patients with DIPF exhibit a lack of erythropoietic response to hypoxaemia, despite the augmented erythropoietin levels. This may reflect a defective bone marrow erythropoietic response in DIPF patients. It is suggested that the pathophysiology of DIPF underlies this mechanism.
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PMID:Erythropoietic response to hypoxaemia in diffuse idiopathic pulmonary fibrosis, as opposed to chronic obstructive pulmonary disease. 1142 4

Hemochromatosis is characterized by an excessive iron deposit in different tissues. Cardiac involvement may be observed in one third of the patients due to hemochromatosis and occurs as a consequence of ferritin accumulation in the heart which on one hand induces alterations in systolic and diastolic ventricular function and on the other hand, an arrythmogenic substrate. The clinical manifestations can be indistinctly related to atrial tachyarrhythmia, ventricular tachyarrhythmia, atrio-ventricular blockade and congestive heart failure, with the first being the most frequent. We present the case of one patient with secondary hemochromatosis to repeated transfusions due to sideroblastic anemia with cardiac involvement, whose initial heart manifestations were recurrent atrial tachyarrhythmia and sustained ventricular tachycardia with syncope for which an automatic defibrillator was implanted.
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PMID:[Ventricular tachycardia and cardiac hemochromatosis]. 1170 44

With the introduction of "hypertransfusion" regimens the extent of disease- and therapy-related hemosiderosis has become the survival limiting factor for patients with beta-thalassemia major as iron transferred with transfusions cannot be excreted by physiological means. Subsequent introduction of deferoxamine therapy for iron elimination and prophylaxis of hemosiderosis has improved prognosis and life quality of these patients considerably. We report our experience with seven adolescent patients with beta-thalassemia and ineffective subcutaneous therapy and severe hemosiderosis-related organ complications. For that reason they received i. v. intensified chelate therapy. The patients were given 70 to 120 mg/kg DFO 7 days a week continuously via a Port-a-cath or Hickman central venous line. Under high-dose i. v. DFO therapy, serum ferritin levels significantly decreased in all patients. Target serum ferritin levels of 3 000 ng/ml were reached after 12 to 20 months of treatment. In 3 of the 5 patients that were treated for longer than 43 months serum ferritin levels even dropped below 2 000 ng/ml. Serum ferritin levels also correlated well with SQUID examinations. Therefore, monitoring of serum ferritin may be useful to monitor patient's compliance and control intensified DFO therapy. Continuous administration of the intensified DFO therapy induced normalization of liver function and left ventricular cardiac function in all patients who are still alive. Two patients died due to cardiac decompensation. In five patients 19 episodes of central catheter-related infections were observed (1.5 infections per 1 000 catheter days). No DFO-associated allergic reactions nor irreversible organ dysfunction were observed. Our results indicate that intensified i. v. DFO therapy is an effective and safe method for treatment of severe organ dysfunction in patients with thalassemia major. The most severe problems are catheter-related infections and inconsistent long-term compliance.
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PMID:Intensification of chelating-therapy in patients with thalassemia major. 1585 2

We describe a case of a female who developed haemosiderosis, in the course of treatment for very severe unstable aplastic anaemia for fourteen years. She was 37 years old at the time of initial diagnosis. Her management consisted of regular blood transfusions aimed at haemoglobin above 8.5 g/dl, antimicrobials, oxymetholone, low dose prednisone and folate. She had received about seventy five units of blood at the start of 2 grams of desferrioxamine with every subsequent blood transfusion. Annual tests of serum ferritin showed progressive increase. She developed skin changes, diabetes mellitus, heart disease, recurrent infections, generalized joint and abdominal pains and liver failure. She died within six weeks of developing congestive heart failure coupled with liver failure due to haemosiderosis despite regular use of desferrioxamine.
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PMID:Transfusion haemosiderosis inspite of regular use of desferrioxamine: case report. 1616 82

The incidence of cardiomyopathy was monitored in a 6-year follow-up study involving 56 transfused thalassemia patients treated with deferoxamine (DFO), deferiprone (L1) or their combination. During this period, five female patients on regular subcutaneous or intravenous DFO presented with cardiac complications. Three patients suffered congestive heart failure and the other two arrhythmias. Four of the five patients maintained serum ferritin levels of about 1 mg/L or below and the fifth about 1.5 mg/L for several years prior to the cardiomyopathy. Cardiac magnetic resonance imaging (MRI) T2* and T2 was performed in four patients after the cardiomyopathy, identifying the presence of moderate-to-heavy siderosis. The treatment of the five patients has since changed, involving mainly the use of L1. Low serum ferritin levels appear to be misleading for detecting cardiac iron overload and this may increase the risk of cardiomyopathy. The MRI T2 and T2* relaxation time measurements are a more accurate method of detecting cardiac iron overload. Chelation therapy using L1 or appropriate L1/DFO combinations can reduce cardiac iron overload and the mortality rate in thalassemia patients.
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PMID:Low serum ferritin levels are misleading for detecting cardiac iron overload and increase the risk of cardiomyopathy in thalassemia patients. The importance of cardiac iron overload monitoring using magnetic resonance imaging T2 and T2*. 1679 47

Chronic hypercoagulable state expressed clinically by thromboembolic events has been described in thalassemia. One of the affected organs is the brain where symptomatic and asymptomatic damage has been reported. The present report describes seven cases who presented with the signs of cerebrovascular accident (CVA), five ischemic and two with hemorrhage. Two of them died. All patients were splenectomized, five received regular blood transfusions, and their ferritin levels were between 1,200 and 3,000 mg %. In addition, four patients had congestive heart failure and atrial fibrillation, and three had "Bronze diabetes," The recommendation on the basis of the results is that well-designed clinical trials are indicated to monitor asymptomatic brain damage by magnetic resonance imaging in splenectomized patients over the age of 20 years, who are not regularly transfused and have a high risk to develop thromboembolic events. In this subset of patients, anticoagulant and/or antiplatelet therapy should be considered. Moreover, treatment of additional complications resulting from iron overload, which may contribute to the etiology of CVA such as cardiac failure and arrhythmia with or without "bronze diabetes," is mandatory.
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PMID:Cerebrovascular accident in beta-thalassemia major (beta-TM) and beta-thalassemia intermedia (beta-TI). 1818 11

HFE-related hereditary haemochromatosis (HH) is an iron overload disease attributed to the highly prevalent homozygosity for the C282Y mutation in the HFE gene. The pathophysiology of this error in iron metabolism is not completely elucidated yet, although deficiency of the iron regulatory hormone hepcidin appears to play a role. Ways of diagnosing iron overload include measurement of the serum iron parameters, i.e. serum transferrin saturation and serum ferritin, by a liver biopsy or by calculating the amount of mobilisable body iron withdrawn by phlebotomies. Clinical signs attributed to HFE-related HH include liver failure, arthralgia, chronic fatigue, diabetes mellitus and congestive heart failure. organ failure can be prevented by phlebotomies starting before irreversible damage has occurred. Therefore, screening to facilitate early diagnosis is desirable in individuals at risk of developing HFE-related iron overload. over time it appeared that the clinical penetrance of the HFE mutations was much lower than had previously been thought. This changed the opinion about a suitable screening modality from case detection, via population screening, to family screening as the most appropriate method to prevent HFE-related disease. However, before the implementation of family screening it is vital to have thorough information on the relevance of the specific health problem involved, on the clinical penetrance of C282Y homozygosity and on the effectiveness of the screening approach.
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PMID:Changing aspects of HFE-related hereditary haemochromatosis and endeavours to early diagnosis. 1807 64

Cardiac damage caused by iron overload toxicity is the main cause of death in thalassemia patients. Biopsy samples of poorly chelated thalassemia patients who suffered congestive cardiac failure (CCF) show extensive iron deposition in the myocardium. In one patient who survived CCF, a cardiac biopsy was performed during the removal of a thrombus caused by a port-a-cath, which was used for the administration of intravenous (iv) deferoxamine (DFO). Ultrastructural pathology studies of the cardiac biopsy indicated extensive iron deposition in myocytes with accumulation of iron mainly in lysosomes, leading in some cases to their disruption. Damage to other intracellular components of the myocytes and loss of myofibers was also observed. The patient became intolerant to iv and subcutaneous (sc) DFO 2 years after the CCF, and was then treated with deferiprone (L1) for 7 years. Within 1 year of L1 treatment at 75-80 mg/kg/day, serum ferritin levels were reduced to <0.45 mg/L and she became asymptomatic, needing no further drugs for her cardiomyopathy. Lowering the L1 dose to 50-70 mg/kg/day caused an increase in serum ferritin levels. Maintenance of normal iron stores during the last 3 years as detected by cardiac and liver magnetic resonance imaging (MRI) T2 and T2* and normalization of serum ferritin levels (<0.15 mg/L) was observed following L1 therapy at 80-85 mg/kg/day. Deferiprone (>80 mg/kg/day) appears to be effective in the rapid clearance of cardiac iron, in the reversal of iron overload related cardiomyopathy, in the maintenance of normal iron stores and the overall long-term survival of thalassemia patients.
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PMID:Myocyte damage and loss of myofibers is the potential mechanism of iron overload toxicity in congestive cardiac failure in thalassemia. Complete reversal of the cardiomyopathy and normalization of iron load by deferiprone. 1827 79

Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents. The mechanisms underlying nitrate tolerance remain incompletely defined and are likely multifactorial. One mechanism seems to be a diminished bioconversion of nitroglycerin, another seems to be the induction of vascular oxidative stress, and a third may include neurohumoral adaptations. Recent studies have revealed that mitochondrial reactive oxygen species (ROS) formation and a subsequent oxidative inactivation of nitrate reductase, the mitochondrial aldehyde dehydrogenase (ALDH-2), play an important role in the development of nitrate and cross-tolerance. The present review focus first on the role of oxidative stress and second on the role of ALDH-2 in organic nitrate bioactivation leading to the development of tolerance and cross-tolerance (endothelial dysfunction) in response to nitroglycerin treatment. Recently, the role of mitochondrial oxidative stress in the development of nitrate tolerance was demonstrated in a mouse model with a heterozygous deletion of manganese superoxide dismutase (MnSOD(+/-)), which is the mitochondrial isoform of this enzyme. Studies from our own laboratory have provided evidence for cross-talk between mitochondrial and cytosolic (Nox-dependent) sources of ROS. We close this review by focusing on the protective properties of the organic nitrate pentaerithrityl tetranitrate, which upregulates enzymes that have strong antioxidative activity, such as heme oxygenase-1 and ferritin, thereby preventing the development of tolerance and endothelial dysfunction.
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PMID:Nitrate tolerance as a model of vascular dysfunction: roles for mitochondrial aldehyde dehydrogenase and mitochondrial oxidative stress. 1930 91


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