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Query: UMLS:C0032285 (pneumonia)
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Cunninghamella bertholletiae is a fungus of the Zygomycetes class, Mucorales order. Only very few cases of disseminated infection have been reported. We observed a new case in a 19 years old man with severe aplastic anemia, due to pulmonary primoinfection and hematologic dissemination. This aplastic anemia failed to respond first to an antithymocyte globulin and steroid treatment and then to cyclosporine A. Deferoxamine was infused weekly to prevent iron overload. During a second antithymocyte globulin and steroid treatment, the patient developed bilateral pneumonia. Culture of the broncho-alveolar washing fluid established the diagnosis by isolation of C. bertholletiae. Despite amphotericin B and 5-fluorocytosine intravenous therapy, the patient died of disseminated infection six days after diagnosis, which was confirmed by necropsy. Underlying conditions, diagnosis and treatment are discussed, together with a review of the literature.
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PMID:Cunninghamella bertholletiae: an uncommon agent of opportunistic fungal infection. Case report and review. 178 Feb 37

In a rat model of Pneumocystis carinii pneumonia, a 3-week infusion of deferoxamine producing concentrations in plasma of > or = 1.5 micrograms m-1 eliminated the trophozoite life cycle stage. Since this concentration is well below that routinely achieved in patients treated for iron overload, deferoxamine has promise as a therapy for AIDS-associated P.carinii pneumonia.
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PMID:Trophozoite elimination in a rat model of Pneumocystis carinii pneumonia by clinically achievable plasma deferoxamine concentrations. 872 89

A 58-year-old woman with a diagnosis of aplastic anemia had been treated with anabolic steroid for mild anemia in 1984. In May 1995, pancytopenia progressed and the patient became dependent on red blood cell transfusions. Chromosome analysis of bone marrow cells revealed trisomy 8 and the patient was thought to have aplastic anemia in transformation to myelodysplastic syndrome. In July 1996, deferoxamine was administered for iron overload. The patient was admitted because of pneumonia on July 31, 1998. Chest computed tomograms showed arteriothrombus of the right pulmonary artery and pulmonary mycosis. Although an antifungal agent was administered, the patient experienced respiratory failure and eventually died of hypovolemic shock due to gastric bleeding from a Dieulafoy ulcer. Autopsy revealed arteriothrombus of hyphae of Mucorales in the right pulmonary artery and right renal artery branch. Cases of mucormycosis occurring in dialysis patients receiving deferoxamine have recently appeared in the literature. Deferoxamine may be a risk factor for mucormycosis. Deferoxamine has been also used in the treatment of iron overload patients with aplastic anemia. Four cases of mucormycosis developing in such patients have been reported in Japan including this case. There may be a relationship between mucormycosis and deferoxamine in patients with aplastic anemia.
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PMID:[Development of arterial thrombus of Mucorales hyphae during deferoxamine therapy in a patient with aplastic anemia in transformation to myelodysplastic syndrome]. 1072 42

Infection is a major complication and the leading cause of death in thalassemia, especially E-beta thalassemia. The spectrum of infections in E-beta thalassemia include mild and severe infections, therapy-related infections such as Yersinia enterocolitica infection associated with desferrioxamine (DFO) therapy, and transfusion-transmitted disease, as well as unique infections such as with pythiosis. Prospective studies in Thailand indicate that patients with E-beta thalassemia had more frequent episodes of both mild and severe infections. The former included upper respiratory tract infection, acute gastroenteritis, cutaneous abscess, and gingivitis. Severe infections occurred more commonly in patients with splenectomy and included septicemia, pneumonia, biliary tract infection, salmonellosis, and urinary tract infection. Responsible organisms were Escherichia coli (26%), Klebsiella pneumoniae (23%), Salmonella (15%), and Streptococcus pneumoniae (13%). Other organisms included Pseudomonas, Staphylococci, Burkholderia pseudomallei (melioidosis), and Aeromonas. Patients undergoing DFO therapy are at risk for Y. enterocolitica infection which may be localized to mesenteric nodes and tonsils or occur as a generalized form such as septicemia. Recently, we have seen a unique infection so-called vascular pythiosis. Patients usually presented with clinical features of vascular occlusion of lower limbs from ascending arteritis and thrombosis. The causative organism, Pythium insidiosum, is fungus-like, in the kingdom Stramenopila, and in the class Oomycetes. The mortality rate is high and the only effective treatment has been early amputation or possibly immunotherapy. The predisposing factors of infections in thalassemia include splenectomy, iron overload, anemia, and granulocyte dysfunctions. General management of infections in thalassemia consist of prevention, i.e., immunization with pneumococcal and hepatitis vaccines, oral penicillins especially in patients with splenectomy, removal of predisposing factors such as gallstones, iron overload, and appropriate antibiotics.
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PMID:Infections in E-beta thalassemia. 1113 34

Iron plays a crucial role in the energy metabolism of microorganisms. Humans have developed iron-withholding mechanisms as a form of non-specific immunity. We describe a patient with iron overload and severe Legionella pneumophila pneumonia. This report emphasizes the importance of early consideration of and appropriate therapy against Legionella for patients with iron overload who present with community-acquired pneumonia.
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PMID:Severe Legionella pneumophila pneumonia in a patient with iron overload. 1247 34

Iron overload is a common acute and long-term event associated with autologous and allogeneic hematopoietic stem cell transplantation (HSCT). In a state of iron excess, free iron becomes available to catalyze the conversion of reactive oxygen species (ROS) intermediates such as superoxide anion (O2*-) and hydrogen peroxide (H2O2) to highly toxic free radicals such as hydroxyl radical (OH*). ROS may help to promote chronic liver disease, sinusoidal obstruction syndrome, idiopathic pneumonia syndrome and bacterial, fungal and other opportunistic infections. Phlebotomy has been effectively and safely used to deplete excess iron stores post-HSCT in thalassemic and other iron-overloaded patients. Intracellular iron levels may also be decreased through pharmacologic chelating agents, while antioxidants such as N-acetylcysteine, glutamine (glutathione precursor) and captopril have been shown to replenish glutathione redox potential and scavenge free radicals. A better understanding of the mechanisms involved in the iron-generated pro-oxidant state associated with HSCT will likely lead to reduced toxicity and improved patient outcomes.
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PMID:Rust and corrosion in hematopoietic stem cell transplantation: the problem of iron and oxidative stress. 1528 99

The incidence of infections among patients with thalassaemia and the role of risk factors for infection are uncertain. We studied the occurrence of infections necessitating hospitalisation in 92 homozygous beta-thalassaemia patients who had been followed longitudinally for decades, and investigated the role of potential risk factors for these infections. Pneumonia accounted for 26% of the infections and fever of unknown origin for 14%. Staphylococcus aureus was the major pathogen possibly related to injections associated with intensive chelation with deferoxamine. There was a significant increase in the rate of infection over time, notably after 15 years. Splenectomy correlated with the incidence of infection (P < 0.001) without being confounded by other variables and with highest frequencies of infections present after 10 years. A direct correlation between iron overload and infection was evident only before the initiation of iron-chelating treatment (P < 0.01). Following initiation of deferoxamine, paradoxically, the infection rate increased (P = 0.046). The combination of splenectomy and deferoxamine treatment was associated with the highest adjusted infection rate. Parathyroid dysfunction and glucose-6-phosphate dehydrogenase deficiency were significantly associated with infection (P = 0.02 and P = 0.04 respectively). The infection rate in thalassaemia is affected mainly by the duration of the disease and is increased by splenectomy and, in the long term, by treatment with deferoxamine.
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PMID:Severe infections in thalassaemic patients: prevalence and predisposing factors. 1670 45

The purpose of the study was to analyze clinical and/or autopsy findings at the time of death among adults with sickle cell disease (SCD) at Howard University in Washington, DC over a 25-year period. A single physician recorded circumstances of death among 141 adult SCD patients he treated and knew well from 1976 to 2001. These findings were determined by autopsy report and/or clinical assessment. In a subset of 31 patients, autopsy records were reviewed for reports of iron deposition in liver and heart and of organ pathology. One hundred and fourteen (80.9%) of the patients had SS phenotype and 66 (46.8%) were female. The mean +/- SD age at death was 36 +/- 11 years. Leading circumstances of death included pulmonary hypertension (PHT) (26.2%), sudden death (23.4%), renal failure (22.6%), infection (18.4%), thromboembolism (14.9%), cardiac diagnoses (12.0%), cirrhosis (11.3%), pneumonia or acute chest syndrome (9.9%), bleeding (7.8%), and iron overload (7.0%). When circumstances of deaths that occurred after 1991 (n = 69) were compared to those that occurred in 1991 or earlier (n = 72), PHT (36.2% vs. 16.6%; P < 0.01) was significantly more common in 1992 or later. Significant associations were found between PHT and thromboembolism and between cirrhosis and iron overload. In this proportional mortality study of adults with SCD, PHT was the leading finding at the time of death. Thromboembolism was associated with PHT, and iron overload was associated with cirrhosis.
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PMID:Circumstances of death in adult sickle cell disease patients. 1692 40

Haemopoietic stem cell transplantation (HSCT) is an important intervention for malignant and non-malignant blood diseases. However, HSCT is also associated with considerable morbidity and mortality, some of which may be related to iron overload. Levels of serum iron are elevated in patients undergoing HSCT as a result of disturbed iron metabolism, pre-transplantation blood transfusions, or cytotoxic therapy for conditioning before HSCT. The complications of iron overload in HSCT patients include infections, mucositis, chronic liver disease (fibrosis progression), sinusoidal obstruction syndrome, and idiopathic pneumonia syndrome. Iron overload has an adverse impact on survival in patients undergoing HSCT for beta-thalassaemia major or haematological malignancies including myelodysplastic syndromes. It has been suggested that all candidates for and all survivors of HSCT should be screened for iron overload at various time points before and after transplantation. Few studies of iron chelation therapy after HSCT have been reported, but one small study has indicated that deferoxamine is at least as effective as phlebotomy in reducing post-transplantation iron overload in patients with beta-thalassaemia major. The new oral chelator deferasirox may be better tolerated than phlebotomy or deferoxamine infusion, and two prospective phase II studies in patients with iron overload after HSCT are now recruiting candidates.
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PMID:The role of iron in patients after bone marrow transplantation. 1905 53

Deferasirox is a new oral iron chelator used to treat transfusional iron overload. We describe a case of a 79-year-old man with myelodysplastic syndrome (MDS) who developed esophagitis induced by deferasirox. He repeatedly received multiple red blood cell transfusions after a diagnosis of MDS. Two years after starting red blood cell transfusions, he was diagnosed with iron overload, and was then started on deferasirox at 1 g/day with about 400 ml of water. He was admitted to our institution because he was unable to swallow his own saliva 1 month after starting deferasirox. Esophagogastroendoscopy revealed white-coated mucosa covering the entire esophagus. A component analysis of biopsy specimens using high-performance liquid chromatography identified deferasirox. Symptoms resolved within about 2 weeks after discontinuing deferasirox, and repeated endoscopy showed marked improvement of esophagitis after 1 month. Re-administration of deferasirox was not attempted. Unfortunately, the patient died due to pneumonia 6 months after administration of deferasirox was started. This is the first report of drug-induced esophagitis associated with deferasirox.
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PMID:First report of drug-induced esophagitis by deferasirox. 2254 95


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