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Are there diagnostic histologic features of porphyria cutanea tarda in liver biopsy specimens?

In a blind review of 485 consecutive liver biopsy specimens, 16 from patients with porphyria cutanea tarda (PCT) and 469 from patients with other diseases, we have evaluated the frequency of the following features: a) needle-shaped cytoplasmic inclusions in liver cells, b) lobular aggregates of histiocytes laden with ceroid and iron, and c) the simultaneous presence of portal inflammation, hemosiderosis and fatty change, in order to ascertain their usefulness in the diagnosis of PCT. Cytoplasmic inclusions and lobular aggregates of macrophages were only found in two specimens, both of them from patients with PCT. The simultaneous presence of portal inflammation, hemosiderin and fat was found in nine patients (56%) with PCT and in nine (1.9%) of those without PCT. The localization of hemosiderin deposits differed between the two groups, being observed in periportal hepatocytes in cases with PCT, whilst it was predominantly found in Kupffer cells with a diffuse lobular distribution in cases without PCT. Thus, the finding in a liver biopsy specimen of hemosiderin in periportal hepatocytes, fatty changes and portal inflammation should alert one to the possible diagnosis of PCT and encourage the utilization of tests to confirm this diagnosis.

Adult↗

Goodpasture's syndrome in a child: natural history and effect of treatment.

An 8-year-old girl with microhematuria of recent onset developed a picture of pulmonary hemosiderosis in the space of 2 months. Some months later while pulmonary involvement was improving severe extracapillary glomerulonephritis developed. Circulating anti-glomerular basement membrane antibody was detected and linear deposition of IgG along glomerular basement membrane was observed. A diagnosis of Goodpasture's syndrome was made and treatment was started with prednisone, cyclophosphamide and periodic plasmapheresis with complete progressive disappearance of circulating anti-glomerular basement membrane antibody. After suspension of plasmapheresis despite immunosuppressive therapy and lack of evidence for circulating anti-glomerular basement membrane antibody, the child went into terminal renal failure. The natural history of the disease in this case and the results of treatment are discussed. To our knowledge this is the first case of Goodpasture's syndrome reported in childhood with demonstration of the presence of anti-glomerular basement membrane antibody.

Anti-Glomerular Basement Membrane Disease↗

How does magnetic resonance imaging represent histologic findings in the equine digit?

Magnetic resonance (MR) imaging is increasingly used in the diagnosis of equine foot pain, but improved understanding of how MR images represent tissue-level changes in the equine foot is required. We hypothesized that alterations in signal intensity and tissue contour would represent changes in tissue structure detected using histologic evaluation. The study objectives were to determine the significance of MR signal alterations in feet from horses with and without lameness, by comparison with histopathologic changes. Fifty-one cadaver feet from horses with a history of lameness improved by palmar digital analgesia (n = 32) or age-matched control horses with no history of lameness (n = 19) were stored frozen before undergoing MR imaging and subsequent histopathological examination at standard sites (deep digital flexor tendon, navicular bone, distal sesamoidean impar ligament, collateral sesamoidean ligament, and navicular bursa). Using MR images, signal intensity and homogeneity, size, definition of anatomic margins, and relationships with other structures were described. Alterations were graded as mild, moderate, or severe for each structure. For each anatomic site examined histologically the structures were described and scored as no changes, mild, moderate, or severe abnormalities, also taking into account adhesion formation within the navicular bursa detected on macroscopic examination. Alterations in MR signal intensity were related to changes at the tissue level detected by histologic examination. A sensitivity and specificity comparison of MR imaging with histologic examination was used to evaluate the significance of MR signal alterations for detection of moderate-to-severe lesions of the deep digital flexor tendon (DDFT), navicular bone, distal sesamoidean impar ligament (DSIL), collateral sesamoidean ligament (CSL) and navicular bursa. Agreement between the MR and histologic grading was assessed for each structure using a weighted kappa agreement. Direct comparison between histology and MR imaging for individual limbs revealed that signal alterations on MR imaging did represent tissue-level changes. These included structural damage, fibroplasia, fibrocartilaginous metaplasia, and hemosiderosis in ligaments and tendons; trabecular damage, osteonecrosis, fibroplasia, cortical defects, and increased vascularity in bone; and fibrocartilage defects. MR imaging had a high sensitivity and specificity for most structures. MR imaging had high specificity for lesions of the DDFT, CSL and navicular bursa, quite high specificity for lesions of the medulla of the navicular bone and its proximal aspect, with moderate specificity for the DSIL, and distal, dorsal and palmar aspects of the navicular bone, and was sensitive for detection of abnormalities in all structures except the dorsal aspect of the navicular bone. When MR and histologic grades alone were compared, there was good agreement between MR and histologic grades for the navicular bursa, DDFT, navicular bone medulla and CSL; moderate-to-good agreement in grades of the distal and palmar aspects of the navicular bone; fair to moderate in grades of the DSIL, and poor agreement for the dorsal and proximal aspects of the navicular bone. The results of this study support our hypothesis and indicate the potential use and limitations of MR imaging for visualization of structural changes within osseous and soft tissue structures of the equine foot.

Animals↗

Nuclear resonance scattering measurement of human iron stores.

Hepatic iron stores were measured noninvasively in 31 patients (thalassemia, hemodialysis, hemosiderosis, refractory anemia) with suspected iron overload, employing a nuclear resonance scattering (NRS) technique. The thalassemia patients were undergoing desferrioxamine chelation therapy during the NRS measurements. The hemodialysis patients were measured before chelation therapy. Iron levels measured by NRS were in general agreement with those determined in liver biopsies by atomic absorption spectroscopy. In addition, NRS measurements from the thorax of some of these patients suggest that this method may also prove useful for clinical assessment of cardiac iron.

Adolescent↗

Initial characterization of the hemolysin stachylysin from Stachybotrys chartarum.

Stachybotrys chartarum is a toxigenic fungus that has been associated with human health concerns, including pulmonary hemorrhage and hemosiderosis. This fungus produces a hemolysin, stachylysin, which in its apparent monomeric form has a molecular mass of 11,920 Da as determined by matrix-assisted laser desorption ionization-time of flight mass spectrometry. However, it appears to form polydispersed aggregates, which confounds understanding of the actual hemolytically active form. Exhaustive dialysis or heat treatment at 60 degrees C for 30 min inactivated stachylysin. Stachylysin is composed of about 40% nonpolar amino acids and contains two cysteine residues. Purified stachylysin required more than 6 h to begin lysing sheep erythrocytes, but by 48 h, lysis was complete. Stachylysin also formed pores in sheep erythrocyte membranes.

Hemolysin Proteins↗

Stachylysin may be a cause of hemorrhaging in humans exposed to Stachybotrys chartarum.

Stachybotrys chartarum is a toxigenic fungus that has been associated with human health concerns such as nasal bleeding in adults and pulmonary hemosiderosis (PH) in infants. Seven of eight strains of S. chartarum isolated from homes of infants with PH in Cleveland, Ohio, and the strain from the lung of an infant with PH in Texas produced stachylysin in tryptic soy broth (TSB), whereas only one out of eight strains isolated from control homes produced stachylysin. However, all strains produced stachylysin when grown on TSB with 0.7% sheep's blood. When stachylysin was injected into Lumbricus terrestis, the erythrocruorin hemoglobin (absorbance peaks at 280 and 415 nm) was released, resulting in a lethal effect. These results support the hypothesis that stachylysin may be one agent responsible for hemorrhaging in humans.

Animals↗

Myocardial biopsy.

The history, technique, complications, and evaluation of myocardial biopsy, particularly in cardiomyopathies, have been reviewed and discussed. As expected, specific histological abnormalities for the diagnosis of cardiomyopathies were hard to obtain in such small fragments of myocardium. Rather, myocardial biopsy at present provides information on the severity and prognosis of cardiomyopathies, especially those with a diffuse disease process. However, morphologic examination is definitely valuable in diagnosing cardiomyopathies, even if it merely confirms the clinical diagnosis, because none of the information presently given by any one diagnostic tool is specific enough to correctly diagnose cardiomyopathy. Endomyocardial biopsy is most useful from a diagnostic standpoint in acute cardiac rejection in transplant recipients as well as in secondary myocardial diseases: myocarditis, amyloidosis, hemosiderosis, glycogen storage disease, sarcoidosis, etc. Advances in biochemical, immunologic, and more specific morphologic analyses will increase the usefulness of myocardial biopsy in diagnosing and assessing the etiology of idiopathic cardiomyopathy.

Biopsy↗

The air bronchogram in interstitial disease of the lungs. A radiological-pathological correlation.

The air bronchogram classically signals an end-air-space or "alveolar" filling process such as alveolar proteinosis and bronchioloalveolar-cell carcinoma. However, it can also occur in interstitial diseases, possibly leading to compressive atelectasis and causing crowding of tissue around open airways. In addition, such disease processes may encroach on distal airways, producing obstructive pneumonia which may then surround open proximal airways, as in sarcoidosis and lymphoma. In mixed "alveolar" and interstitial processes such as Pneumocystis carinii pneumonia and the late stages of hemosiderosis, "alveolar" filling may mask the interstitial disease.

Adenocarcinoma, Bronchiolo-Alveolar↗

Pulmonary hemorrhage associated with systemic lupus erythematosus in children.

Four children with systemic lupus erythematosus (SLE) and pulmonary hemorrhage are discussed. Radiologists should be aware of the possibility of such bleeding when confronted with diffuse parenchymal abnormalities in a child, particularly if there is (a) evidence of unexplained blood loss or (b) signs and symptoms of collagen vascular disease. Pulmonary hemorrhage may occur long before SLE is suspected and appear identical to idiopathic pulmonary hemosiderosis.

Adolescent↗

Pediatric pulmonary disease: assessment with high-resolution ultrafast CT.

High-resolution computed tomography (HRCT) is widely used to assess pulmonary parenchymal disease in adults. The authors used ultrafast CT with 3-mm collimation and a 100-msec scan time to obtain HRCT scans in 36 children (mean age, 49.4 months). Clinical diagnoses included normal lungs (n = 6), cystic fibrosis (n = 12), obliterative bronchiolitis (n = 6), idiopathic pulmonary hemosiderosis (n = 2), and other lung diseases (n = 10). The HRCT scans and chest radiographs were reviewed separately in blinded fashion. Pulmonary parenchymal abnormalities were categorized into interstitial, airspace, and airway processes. Nine patients with normal chest radiographs had abnormal HRCT scans. In five other patients, the extent of abnormal lung parenchyma was considerably greater on HRCT scans than on chest radiographs. HRCT scans allowed accurate characterization of the type of lung process in 24 of 30 patients when compared with clinical or biopsy findings. Early HRCT findings in cystic fibrosis included lobular air trapping, bronchial wall thickening, and centrilobular nodules. The use of cine CT with high-resolution techniques is feasible in children too young or too sick to hold their breath. HRCT may enable early detection and characterization of pulmonary disease and depiction of the extent of lung abnormality.

Bronchiolitis Obliterans↗

Dual gradient-echo in-phase and opposed-phase hepatic MR imaging: a useful tool for evaluating more than fatty infiltration or fatty sparing.

A T1-weighted gradient-echo in-phase and opposed-phase sequence has become a routine part of every hepatic magnetic resonance (MR) imaging protocol. Although this sequence is primarily used to identify common pathologic conditions, such as diffuse or focal steatosis and focal fatty sparing, it is also helpful in detection of pathologic entities associated with T2* effects owing to the double-echo approach. Thus, pathologic conditions such as hemochromatosis or hemosiderosis can be identified and characterized with a high level of confidence. In cases of iron storage disease, the hepatic parenchymal signal intensity decreases on the image with the longer echo time due to the continued decay of the transverse magnetization. In addition, susceptibility artifacts can be easily detected and characterized with in-phase and opposed-phase MR imaging. Metallic objects demonstrate a larger susceptibility artifact on the image with the second or longer echo time, which is usually the in-phase image. Finally, intrahepatic pneumobilia can be identified with the T1-weighted gradient-echo in-phase and opposed-phase sequence because gas also causes a susceptibility artifact, which is more pronounced on the image with the longer echo time. A complete understanding of both the chemical shift cancellation artifact and the T2* effects of the in-phase and opposed-phase sequence is important for correct interpretation of hepatic MR images.

Diagnosis, Differential↗

Long-term results of functional hemispherectomy for intractable seizures.

OBJECTIVE: From May 1989 to April 1997, functional hemispherectomy was performed in 8 cases of intractable seizures. We retrospectively analyzed our experience to evaluate the seizure control and complications of this surgical technique. METHODS: Following Dr. Rasmussen's model of functional hemispherectomy or performing a modification of this operation, we removed the sensorimotor cortex and temporal lobe associated with disconnection of the remaining portions of the frontal lobe and parieto-occipital lobe. RESULTS: All the patients were followed up for 3-11 years (mean 6.7 years). Satisfactory seizure control was obtained in all the cases. Life quality improved and patients worked or studied well after the operations. No cases of superficial cerebral hemosiderosis were found. CONCLUSION: Modified functional hemispherectomy may allow the patients to lead more independent lives by leading to a cessation or reduced frequency of seizures.

Adolescent↗

Disconnective hemispherectomy.

Hemispherectomy is a valuable procedure in the management of seizure disorders caused by unilateral hemispheric disease. Modifications to anatomical hemispherectomy have been proposed to reduce the incidence of superficial cerebral hemosiderosis and hydrocephalus while still achieving seizure control. We report on the modification of a previously described disconnective form of hemispherectomy. We used this procedure on 2 children, with the aid of stereotactic navigation in 1 of the 2 cases. This disconnection was achieved via a transventricular route with minimal cortical resection or disruption of the blood supply. Over the 20 months of follow-up, 1 patient achieved complete seizure control, and 1 patient achieved control of previously incapacitating seizures with few minor seizures persisting. Motor function and speech significantly improved in both patients. Blood loss during the two procedures was significantly less than that reported for anatomical hemispherectomy, and so far there have been no signs of postoperative complications. The hospital stay was limited to 7-14 days after surgery.

Cerebral Cortex↗

Hemimegalencephaly and intractable epilepsy: complications of hemispherectomy and their correlations with the surgical technique. A report on 15 cases.

Hemispherectomy is required in most cases of hemimegalencephaly in order to control epilepsy refractory to medical treatment. Although there is a general agreement on the effectiveness of the procedure in controlling the seizure disorder, the choice of the surgical technique is still a subject of debate. In particular, anatomical hemispherectomy is blamed to be associated with a higher incidence of surgical complications, namely hydrocephalus and hemosiderosis, than other less ablative operations such as functional hemispherectomies. A series of 15 children with hemimegalencephaly, who had undergone anatomical hemispherectomy (11 cases), functional hemispherectomy (2 cases), and hemidecortication (2 cases) at the Pediatric Neurosurgery Section, Catholic University Medical School, Rome, is reported. Twelve of these patients presented with one or more complications in their postoperative course. Temporary complications, which resolved spontaneously or following medical therapy, included fever, wound breakdown, worsening of preoperative motor deficit, unilateral third cranial nerve deficit, dystonia, and anemia. In 8 patients, postoperative complications led to a second surgical procedure. A CSF shunt was necessary in 5 children, to control a secondary hydrocephalus. Two subjects underwent a toilette of the residual cavity because of persisting chemical abnormalities in CSF parameters. In a child a cranioplasty procedure was necessary as a consequence of an infection of the hemicranial bone flap. There was no apparent correlation between the rate and the type of complications with a specific surgical procedure. On the other hand, the age factor appeared to play an important role in the occurrence of secondary hydrocephalus, as all 5 children with this complication were less than 9 months old at the time of the hemispherectomy. Surgical mortality was nil in this series.

Brain↗

Improvement of cardiac function in thalassemia major treated with L-carnitine.

INTRODUCTION: Heart disease secondary to chronic anemia and hemosiderosis remains the major cause of morbidity and mortality in thalassemic patients. Chronic anemia and the tissue hypoxia it induces impair free fatty acid oxidation and ATP production in myocardial cells. The use of L-carnitine, a butyric acid derivative, may help overcome some of these defects. OBJECTIVE: To investigate the effect of L-carnitine therapy on cardiac function in thalassemia major patients. MATERIALS AND METHODS: Cardiac function was evaluated in 30 patients attending our clinic. The mean (+/-SD) age was 15.87 +/- 3.19 years. The studies we performed included echocardiography, Doppler and multigated equilibrium radionuclide angiography (MUGA). Systolic and diastolic function was evaluated before starting L-carnitine treatment and after 6 months of oral L-carnitine (50 mg/kg/day). RESULTS: Echocardiography studies revealed no significant changes in systolic and diastolic function after L-carnitine therapy (p > 0.05). Analysis of the data taken by MUGA performed in 20 of the patients, however, showed a significant improvement of diastolic function after 6 months of L-carnitine therapy. The mean peak filling rate (end-diastolic volume/s) increased from 3.15 +/- 1.06 to 3.61 +/- 1.68 (p < 0.03). The time to peak (during filling) decreased significantly from 143.45 +/- 42.04 to 117.70 +/- 24.40 s (p < 0.02). Systolic function showed a significant increase in the left ventricular ejection fraction from 58.25 +/- 9.92 to 63.95 +/- 10.11% (p = 0.0001). CONCLUSION: L-carnitine may be an effective drug for improving the cardiac status of thalassemic patients. MUGA is the most accurate technique of those used here for assessing left ventricular function in these patients.

Adolescent↗

Treatment of beta-thalassemia patients with recombinant human erythropoietin: effect on transfusion requirements and soluble adhesion molecules.

The most common single genetic disorder and a major public health issue in Greece and other Mediterranean countries is beta-thalassemia. Current therapeutic approaches for homozygous beta-thalassemia entail blood transfusions and iron chelation therapy with deferoxamine or deferiprone for preventing tissue hemosiderosis. Recently, much effort has focused on various inducers of fetal hemoglobin (HbF) such as recombinant human erythropoietin (rHuEPO), especially in beta-thalassemia intermedia. Ten adult patients, 5 with beta-thalassemia major and 5 with beta-thalassemia intermedia, received 150 IU/kg rHuEPO (epoetin-alpha) subcutaneously three times a week. Seven patients were transfused every 14-30 days and 3 with beta-thalassemia intermedia were only occasionally transfused. The minimum duration of treatment was 12 weeks in order to define if there was any response. Transfusion intervals were modified according to the rHuEPO response to maintain stable Hb values. Lower transfusion requirements were observed in 5 patients after rHuEPO treatment (p = 0.028). In the 3 non-transfused patients, Hb values increased, and the patients are still being treated and followed up for a period ranging from 14 weeks to 2 years. Two patients with thalassemia major discontinued treatment after 12 weeks, as they did not achieve any response regarding transfusion requirements or Hb values. Pretreatment serum transferrin receptor levels were higher than in controls (p < 0.001) and significantly increased following rHuEPO treatment (p = 0.027). Patients had higher serum endothelin-3, sICAM-1 and sE-selectin values before rHuEPO treatment compared to controls (p < 0.001, p < 0.001 and p = 0.016, respectively), but these values were not altered during treatment. HbF values presented a slight, non-significant increase. rHuEPO treatment has a beneficial effect in transfusion-dependent beta-thalassemia patients. Although a slight increase in HbF levels was observed, other possible mechanisms are probably involved. None of our patients experienced thrombotic complications and a rise in blood pressure.

Adolescent↗

GH secretion in thalassemia patients with short stature.

The physiological role of GH secretion on growth retardation remains to be elucidated especially in patients with beta-thalassemia. In the present study, we investigated IGF-1 circulating levels as well as GH release following GHRH alone or combined with some inhibitors of somatostatin: pyridostigmine and arginine. In thalassemic patients lower IGF-1 circulating levels appear to be negatively correlated with both aspartate aminotransferase and alanine aminotransferase as well as with ferritin circulating levels indicating a probable role of hepatic hemosiderosis in IGF-1 production. The authors however suggest that reduced IGF-1 secretion is not the main cause of growth retardation since this would have elicited an enhanced response of GHRH in the presence of a normal hypothalamic pituitary axis. In contrast, they noticed that GH response to GHRH when expressed as area under the curve was lower in thalassemic patients compared to controls. The combination of GHRH with either pyridostigmine or arginine induced a GH secretion in thalassemics which was comparable to that of controls. The results of this study lead to conclude that the alteration of GH secretion is due, in such patients, to an increased somatostatin activity.

Adolescent↗

Reticuloendothelial phagocytic function in children with beta-thalassemia major.

Reticuloendothelial phagocytic capacity (REPC) was determined in 14 children with beta-thalassemia major, by means of technetium 99m sulfur colloid uptake, who had not had splenectomy. No difference was observed in the REPC between patient and controls. The REPC of liver and spleen were evaluated separately by determining the half-time for the clearance of 99mTc from the blood. The REPC of both liver and spleen in patients was expected to be decreased when compared with controls; however, we found that the REPC of the liver was increased in patients and that there was no difference between patients' and controls' spleen values. This suggests that chronic anemia and hemosiderosis do not alter the REPC in beta-thalassemia major.

Adolescent↗