Idiopathic pulmonary haemosiderosis. Epidemiology, pathogenic aspects and diagnosis.
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Idiopathic pulmonary haemosiderosis (IPH) is a rare clinical entity characterized by recurrent episodes of diffuse alveolar haemorrhage, often presenting with haemoptysis. Many patients have iron deficiency anaemia due to deposition of haemosiderin iron in the alveoli, and eventually develop moderate pulmonary fibrosis. Typically, intensive search for an aetiology ends up negative. There is no evidence of pulmonary vasculitis or capillaritis. The aetiology is obscure, but may be an immunological or toxic mechanism causing a defect in the basement membrane of the pulmonary capillary. IPH affects both children and adults. During an acute episode, a chest X-ray demonstrates bilateral, alveolar infiltrates. Sputum examination discloses haemosiderin-laden alveolar macrophages. Diagnosis is established by lung biopsy (fiber-optic or thoracoscopic), showing large numbers of haemosiderin-laden macrophages in the alveoli and without evidence of capillaritis or deposition of immunoglobulins. Corticosteroids and/or immunosuppressive drugs may be effective during an acute bleeding episode, and may in some patients improve symptoms and prognosis on the long-term, but the response to treatment displays great interindividual variation. (+info)
Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds.
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BACKGROUND AND PURPOSE: Patients with spontaneous intracerebral hemorrhage (ICH) frequently have small areas of signal loss on gradient-echo T2*-weighted MR images, which have been suggested to represent remnants of previous microbleeds. Our aim was to provide histopathologic support for this assumption and to clarify whether the presence and location of microbleeds were associated with microangiopathy. METHODS: We performed MR imaging and correlative histopathologic examination in 11 formalin-fixed brains of patients who had died of an ICH (age range, 45-90 years). RESULTS: Focal areas of signal loss on MR images were noted in seven brains. They were seen in a corticosubcortical location in six brains, in the basal ganglia/thalami in five, and infratentorially in three specimens. Histopathologic examination showed focal hemosiderin deposition in 21 of 34 areas of MR signal loss. No other corresponding abnormalities were found; however, hemosiderin deposits were noted without MR signal changes in two brains. All specimens with MR foci of signal loss showed moderate to severe fibrohyalinosis, and there was additional evidence of amyloid angiopathy in two of those brains. CONCLUSION: Small areas of signal loss on gradient echo T2*-weighted images indicate previous extravasation of blood and are related to bleeding-prone microangiopathy of different origins. (+info)
Alveolar haemorrhage in a case of high altitude pulmonary oedema.
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A case of high altitude pulmonary oedema (HAPE) in a climber who made a rapid ascent on Mt McKinley (Denali), Alaska is described. The bronchoalveolar lavage (BAL) fluid contained increased numbers of red blood cells and an abundance of haemosiderin laden macrophages consistent with alveolar haemorrhage. The timing of this finding indicates that alveolar haemorrhage began early during the ascent, well before the onset of symptoms. Although evidence of alveolar haemorrhage has been reported at necropsy in individuals dying of HAPE, previous reports have not shown the same abundance of haemosiderin laden macrophages in the BAL fluid. These findings suggest that alveolar haemorrhage is an early event in HAPE. (+info)
Anthracycline cardiotoxicity in a black rhinoceros (Diceros bicornis): evidence for impaired antioxidant capacity compounded by iron overload.
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Two weeks before dying of congestive heart failure, a juvenile black rhinoceros (Diceros bicornis minor) received a single low dose of doxorubicin as part of combination chemotherapy for acute lymphoblastic leukemia. Diffuse hemosiderosis was present at necropsy in a pattern indicative of dietary iron overload, but unique iron-positive degenerative lesions were found in isolated myocardiocytes. Serum analyses revealed hyperferremia, 87% transferrin saturation, and 5- to 10-fold elevations in ferritin concentration, reflecting markedly increased tissue iron stores. Since both toxic and therapeutic effects of anthracyclines are mediated by formation of reactive free radicals via iron-catalyzed reactions, these observations suggest that iron overload may have enhanced myocardial susceptibility to cardiotoxic effects of doxorubicin. Impairments in other myocardial antioxidant defenses, such as deficiencies in catalase and glutathione S-transferase that are known to exist in rhinoceros erythrocytes, may have been underlying factors contributing to an inherent sensitivity of rhinoceros tissues to oxidant-induced injury. (+info)
Low-frequency low-field magnetic susceptibility of ferritin and hemosiderin.
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Low-frequency low-field magnetic susceptibility measurements were made on four samples of mammalian tissue iron oxide deposits. The samples comprised: (1) horse spleen ferritin; (2) dugong liver hemosiderin; (3) thalassemic human spleen ferritin; and (4) crude thalassemic human spleen hemosiderin. These samples were chosen because Mossbauer spectroscopic measurements on the samples indicated that they exemplified the variation in magnetic and mineral structure found in mammalian tissue iron oxide deposits. The AC-magnetic susceptometry yielded information on the magnetization kinetics of the four samples indicating samples 1, 2, and 3 to be superparamagnetic with values of around 10(11) s(-1) for the pre-exponential frequency factor in the Neel-Arrhenius equation and values for characteristic magnetic anisotropy energy barriers in the range 250-400 K. Sample 4 was indicated to be paramagnetic at all temperatures above 1.3 K. The AC-magnetic susceptometry data also indicated a larger magnetic anisotropy energy distribution in the dugong liver sample compared with samples 1 and 3 in agreement with previous Mossbauer spectroscopic data on these samples. At temperatures below 200 K, samples 1-3 exhibited Curie-Weiss law behavior, indicating weak particle-particle interactions tending to favor antiparallel alignment of the particle magnetic moments. These interactions were strongest for the dugong liver hemosiderin, possibly reflecting the smaller separation between mineral particles in this sample. This is the first magnetic susceptometry study of hemosiderin iron deposits and demonstrates that the AC-magnetic susceptometry technique is a fast and informative method of studying such tissue iron oxide deposits. (+info)
Benign transport of breast epithelium into axillary lymph nodes after biopsy.
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The most important prognostic indicator of distant metastasis in breast cancer is histologic documentation of axillary lymph node metastasis. Controversy exists about the importance of micrometastases (< 0.2 cm), and current pathology practice includes a careful search for their presence. We describe the histologic findings in a series of axillary lymph node dissections taken approximately 2 weeks after breast biopsy. Each case has limited presence of epithelial cells in the subcapsular sinus of a draining lymph node that we attribute to mechanical transport of tumor and/or normal breast epithelium secondary to the previous surgical or needle manipulation. These cells were accompanied by hemosiderin-laden macrophages and damaged RBCs. While the clinical implication of these findings is unknown, we believe that it will be of no clinical significance and have no untoward prognostic effect. (+info)
Iron overload and kidney lysosomes.
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Iron overload has been associated with damage of the liver and other organs of patients with primary or secondary increased iron load. In order to study the effect of iron overload on the pathophysiology of kidney lysosomes, experimentally induced iron overload models were employed. Iron overload was achieved through intraperitoneal injections of Fe-dextran (Imferon) in male rats, at different final iron concentrations (825 and 1650 mg/kg, single and double dose groups respectively). Controls were injected with dextran following a similar protocol. The animals were killed at different time points after the last injection. Subcellular fractionation studies of kidney homogenates were carried out by differential centrifugation and density gradient centrifugation. The kidney iron load was increased with both doses. Iron appeared to accumulate mainly in the lysosomes, bringing about distinct changes in the behaviour of the organelles as judged by subcellular fractionation studies. Lysosomes became more fragile and showed increased density. The extent of the above changes seemed to correlate with the extent and duration of iron accumulation and could be reversed when the iron load was reduced. (+info)
Ferritin iron absorption in man.
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The iron absorption from ferritin and hemosiderin biosynthetically labeled with radioiron was studied in 108 subjects. The geometric mean absorption of ferritin iron in both normal and iron-deficient subjects was 1.9 percent. Its mean absorption ranged from 0.9 percent in normal subjects to 2.5 percent in subjects with moderate iron deficiency and 5.7 percent in subjects with marked iron deficiency. The administration of this iron compound with vegetals in a meal showed distinctly lower absorption values than the absorption from either maize, wheat, or soybean. Ferritin iron absorption was also different from that of ferric chloride when they were administered together as a drink or mixed with maize or liver. The iron absorption from ferritin was markedly increased when it was administered with either meat or liver, but it did not reach the absorption level of these foods. It is still to be elucidated whether the difference in iron absorption between ferritin and vegetable foods administered together reflect that this iron is incompletely miscible with a nonheme iron pool or that it really forms a third iron pool. (+info)