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)

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 pilocytic astrocytoma is only rarely associated with gross intratumoral hemorrhage despite rich vasculature and blood vessel changes, accompanied often by perivascular depots of hemosiderin. We report an unusual case of pigmented cerebellar pilocytic astrocytoma presenting with posttraumatic hemorrhage in a 38-year-old man with no history related to the tumor. CT and MRI examination after head injury demonstrated unexpectedly the cystic lesion of 2 cm in diameter in the region of the right cerebellar hemisphere and vermis. The lesion was associated with hematoma and it was surgically removed 3 weeks after trauma. Histopathological examination revealed pilocytic astrocytoma tissue with broad hemorrhagic changes and with an unusual pattern of massive pigmentation of the cytoplasm of pilocytic astrocytes, consistent with hemosiderosis. Positive stains for iron and ferritin and ultrastructural study confirmed deposition of hemosiderin granules in the tumour cells. There was no evidence of melanin or melanosomes. This finding of hemosiderin accumulation in the cytoplasm of neoplastic astroglia seems to be analogous to post-hemorrhagic pigmentation of the normal Bergmann glia and subpial astrocytes. In the literature, the examples of neuroepithelial tumors with hemosiderin pigmentation of tumor cells have been rarely documented. To our knowledge, this is the first reported case of pigmented pilocytic astrocytoma exhibiting extensive intracellular hemosiderin deposition.
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PMID:Hemosiderin pigmentation of tumour cells in cerebellar pilocytic astrocytoma associated with post-traumatic hemorrhage in adults. 1624 13

Chronic graft-vs.-host disease (cGVHD) occurs in 20-50% of patients who survive for at least 100 d after allogeneic stem cell transplantation (SCT). cGVHD includes scleroderma-like skin changes, chronic cholangitis, obstructive lung disease and general wasting syndrome. Polymyositis or myopathy are rare manifestations of cGVHD with approximately 40 reported cases. Polymyositis accompanied by hemosiderin deposits in cGVHD has been reported only once, and there are no reports on lipofuscin deposits in skeletal muscle cells in cGVHD. We report here on a 56-yr-old male who underwent allogeneic SCT in 1999 for osteomyelofibrosis and progressive hematopoietic insufficiency. In February 2004, the patient was hospitalized for progressive muscular weakness with loss of the ability to walk. Laboratory tests demonstrated normal values for serum creatine kinase, aldolase and lactic dehydrogenase; the ferritin level was highly elevated. The femoral muscle biopsy showed mostly perifascicular atrophy as well as numerous subsarcolemmal hemosiderin and lipofuscin deposits. Intravenous administration of the chelating agent deferoxamine was ineffective. Three weeks later the patient died of aspiration pneumonia. Interestingly, autopsy disclosed moderate hemosiderin deposits in the liver, the organ usually involved in hemosiderosis.
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PMID:Hemosiderin deposits in chronic graft-vs.-host disease related myopathy. 1631 67

Therapy with either deferiprone (DFP) or deferoxamine (DFO) is inadequate in achieving negative iron balance in many patients with thalassemia. There are mounting theoretical, experimental, and clinical evidences of increased efficacy when therapy includes both chelating agents. DFP and DFO chelate excess iron in different ways without affecting each other's metabolism. When both chelators are administered simultaneously, they interact either in an additive or synergistic manner, probably through "shuttling" iron from DFP to DFO. Iron-balance studies have shown that the use of both agents on the same day can induce negative iron balance in all patients. Long-term combined therapy with DFO with DFP results in considerable reduction of both ferritin levels and liver iron concentration as well as significant improvement in cardiac siderosis and function. This therapeutic regimen is well tolerated and safe, even though it may be related to a small increase in the incidence of agranulocytosis compared with DFP monotherapy. Apart from using both agents simultaneously, sequential administration of DFP and DFO has also shown promising results. Combining the available iron chelators offers many therapeutic options that can be tailored to each patient individually. It is an exciting advance in treating hemosiderosis in thalassemic patients.
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PMID:Combined therapy with deferoxamine and deferiprone. 1633 63

Iron-induced organ degeneration is the main factor of mortality in patients with thalassemia major. Since chelation therapy is at a turning point, from the laborious parenteral route to the use of new promising oral agents, we investigated the current status of survival of these patients to present reliable data that will be useful in future comparative studies. Survival probabilities were estimated by the Kaplan-Meier method, and results were compared by the log-rank test in a total of 647 thalassemic patients (pts) (52% males) born between 1/1/58 and 1/2/04. Terminal follow-up was 1/12/04. All transfusion-dependent pts monitored in our center, or in frequent contact if they had moved elsewhere, were strictly selected, excluding all rarely transfused or intermediate cases. Pts born before 1/1/75 were classified in group A (n = 366), while pts born later were included in group B (n = 281). According to the last 5 years' mean serum ferritin level, pts were divided into three hemosiderosis groups: (1) mild (<2000 microg/L) 49%, (2) moderate (2000-4000 microg/L) 28%, and (3) severe (>4000 microg/L) 23%. Of the 647 pts, 115 died (mean age: 22.6 +/- 6.2 years), most frequently by heart failure (71.3%) followed by sepsis (7.8%). Life expectancy in the entire population was up to 59% at 46 years. Survival was higher for pts born after 1975 than those before (P < .001). Statistically significantly different survival probabilities were found between groups with mild, moderate, or severe hemosiderosis (P < .001). Effective management with improved chelation therapy could lead to better results.
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PMID:Longitudinal study of survival and causes of death in patients with thalassemia major in Greece. 1633 95

Lemurs kept in captivity have been reported to be highly prone to accumulate excessive amounts of iron in tissues (hemosiderosis). Diagnosis of the condition is most commonly made during a postmortem examination because an antemortem diagnosis requires a liver biopsy, a procedure that may not be well tolerated by all animals. The lack of a noninvasive method to evaluate iron status in captive lemurs limits investigators' ability to effectively screen animals for the presence of hemosiderosis, and to detect the condition early when treatment protocols are most effective. This study was conducted in an effort to provide data regarding iron analyte values in healthy captive lemurs of multiple species. The relationship of various iron-related metabolites was evaluated in 177 clinically normal lemurs of nine different species. Serum iron (sI), total iron binding capacity (TIBC), and ferritin concentration were measured directly and the percent transferrin saturation (TS) was calculated. Significant differences in various iron metabolites were observed among several species, suggesting that normal reference values for iron metabolites in lemurs may need to be developed on a species by species basis.
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PMID:Comparison of serum iron, total iron binding capacity, ferritin, and percent transferrin saturation in nine species of apparently healthy captive lemurs. 1655 May 26

Transfusional iron overload may occur in the lungs. We hypothesized that quantitating siderophages in the bronchoalveolar fluid (BALF) of heavily transfused patients may prove to be a useful tool in determining lung iron overload in transfusion-dependent patients. The study included six patients (7-20 years) with thalassemia major (TM) who had received multiple blood transfusions, one with hereditary spherocytosis (four blood transfusions) and one with sickle cell disease (never transfused); they were compared to three children with idiopathic pulmonary hemosiderosis (IPH) (2.5-7.0 years) as positive controls. Fiberoptic bronchoscopy with bronchoalveolar lavage was performed in seven patients under general anesthesia for elective surgery and the rest were bronchoscoped electively under sedation. Spirometry was also performed in eight patients. There was no significant difference between children with TM and IPH in siderophages as percentage of total count (95% CI -31.0 to 1.5, P = 0.068). There were positive relationships between both mean serum ferritin values during the preceding year and the total number of units of transfused blood, and percent siderophage count among multiply transfused patients (P = 0.010, P = 0.052, respectively); similar findings were noted for the Golde score (P = 0.001, P = 0.031, respectively). None of the patients showed lung function impairment. In conclusion, in this small study, we found that the BALF of multiply transfused patients with benign hematological disorders contain similar numbers of siderophages to that of patients with IPH; this is strongly suggestive of secondary pulmonary hemosiderosis. The correlation between the patients' serum ferritin, and the BALF siderophages suggests that the later may serve as a marker of pulmonary iron overload in patients requiring blood transfusion and appear to be more sensitive than standard pulmonary function tests.
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PMID:Quantification of siderophages in bronchoalveolar fluid in transfusional and primary pulmonary hemosiderosis. 1687 95

Lemurs in captivity progressively accumulate iron deposits in a variety of organs (hemosiderosis) including duodenum, liver, and spleen throughout their lives. When excessive, the toxic effects of intracellular iron on parenchymal cells, particularly the liver, can result in clinical disease and death. The pathogenesis of excessive iron storage in these species has been attributed to dietary factors related to diets commonly fed in captivity. Tissue iron stores can be directly estimated by tissue biopsy and histologic examination, or quantitated by chemical analysis of biopsy tissue, However, expense and risk associated with anesthesia and surgery prevent routine use of tissue biopsy to assess iron status. A noninvasive means of assessing total body iron stores is needed to monitor iron stores in lemurs to determine whether dietary modification is preventing excessive iron deposition, and to monitor potential therapies such as phlebotomy or chelation. Serum ferritin concentration correlates with tissue iron stores in humans, horses, calves, dogs, cats, and pigs. Serum ferritin is considered the best serum analyte to predict total body iron stores in these species and is more reliable than serum iron or total iron binding capacity, both of which may be affected by disorders unrelated to iron adequacy or excess including hypoproteinemia, chronic infection, hemolytic anemia, hypothyroidism, renal disease, and drug administration. We have developed an enzyme-linked immunosorbent assay to measure serum ferritin in lemurs. The assay uses polyclonal rabbit anti-human ferritin antibodies in a sandwich arrangement. Ferritin isolated from liver and spleen of a black and white ruffed lemur (Varecia variegata variegata) was used as a standard. Ferritin standards were linear from 0 to 50 microg/L. Recovery of purified ferritin from lemur serum varied from 95% to 110%. The within-assay variability was 4.5%, and the assay-to-assay variability for three different samples ranged from 10% to 17%. The assay also measures serum ferritin in several other lemur species.
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PMID:Enzyme-linked immunosorbent assay to quantitate serum ferritin in black and white ruffed lemurs (Varecia variegata variegata). 1731 22

A 30-year-old woman with transfusion-dependent, homozygous beta-thalassemia major and transfusional hemosiderosis had 2 successful pregnancies after ovulation induction and in vitro fertilization. Treatment with subcutaneous desferrioxamine (DF) was discontinued before the conception but restarted at 6 months of gestation. Elective cesarean section was performed at 35 weeks of pregnancy because of partial placenta previa. The infant was clinically normal. At the time of delivery, the maternal serum ferritin was 2000 ng/mL, serum iron/iron binding capacity (SI/TIBC) were 274/380 microg/dL, and % saturation 72%. Serum ferritin level in the infant was 42 ng/mL, SI/TIBC were 53/222 microg/dL, and % saturation 23%. During a twin pregnancy 2 years later, DF therapy was totally withheld. Elective cesarian section was performed at 36 weeks of gestation. Both twins were clinically normal. At delivery, the maternal serum ferritin was 1700 ng/mL, SI/TIBC 447/450 microg/dL, and % saturation 99%. Serum ferritins of the twins were 227 and 203 ng/mL, SI/TIBC were 30/182 and 27/203 microg/dL, and % saturations 16% and 13%. Despite elevated iron studies in the mother during both pregnancies, the SI/TIBC of the infants were quite low. In the first pregnancy in which DF was administered in last months of gestation, a low level of serum ferritin was present in the newborn that was even lower at 3 months of age. In the second pregnancy, high normal, levels of ferritin were present in both twin newborns. Despite comparable gestational ages, hemoglobin levels were lower in the first pregnancy than the second. These studies indicate that very high maternal levels of SI/TIBS and serum ferritin were not associated with increased fetal SI/TIBC, which were, in fact, quite low. Because of the different fetal ferritin levels in the 2 pregnancies, it is possible that treatment of the mother with DF in the last weeks of pregnancy may have resulted in depletion of fetal iron stores.
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PMID:Iron studies in infants born to an iron overloaded mother with beta-thalassemia major: possible effects of maternal desferrioxamine therapy. 1735 94


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