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PubMed2006

Pulmonary haemosiderosis in infants and children.

Pulmonary haemosiderosis (PH) results from recurrent bleeding into alveolar spaces and interstitial lung tissue. If untreated, fibrosis and restrictive lung disease will develop and may lead to death. A distinction can be made between primary and secondary pulmonary haemosiderosis as a manifestation of auto-immune small vessel vasculitides, coagulation disorders or diseases with increased venous pressure. Interestingly, in some cases of 'idiopathic' PH, exposure to moulds and van Willebrand's disease may contribute to the pathogenesis. Haemosiderosis usually begins with haematemesis. Anaemia, alveolar infiltrates on chest x ray and siderophages in broncho-alveolar lavage fluid are diagnostic factors. Immunosuppressive treatment has improved the prognosis in recent years.

Age Factors↗
PubMed2005

Coeliac disease as a cause of unusually severe anaemia in a young man with idiopathic pulmonary haemosiderosis.

Idiopathic pulmonary haemosiderosis (IPH) is characterized by a triad of recurrent episodes of alveolar haemorrhage, haemoptysis and iron deficiency anaemia. The combination of IPH and coeliac disease (CD) is extremely rare though both diseases may have a common pathogenetic link. As illustrated by our case CD should be specifically looked for in patients with IPH, especially those in whom the severity of anaemia is disproportionate to radiologic findings even in the absence of gastrointestinal symptoms since both diseases may benefit from a gluten-free diet.

Adult↗
PubMed2005

Mode of action of butoxyethanol-induced mouse liver hemangiosarcomas and hepatocellular carcinomas.

Chronic exposure to 2-butoxyethanol resulted in an increase in liver hemangiosarcomas and hepatic carcinomas in male mouse liver. No increase in liver neoplasia was observed in similarly exposed male and female rats or female mice. We have proposed that the production of liver neoplasia in the male mouse is the result of oxidative damage secondary to the hemolytic deposition of iron in the liver. Our working hypothesis is that the mode of action of butoxyethanol-induced mouse liver hemangiosarcomas and hepatic neoplasia involves the metabolism of 2-butoxyethanol to butoxyacetic acid which results in the induction of RBC hemolysis. This hemolytic response is translated into the accumulation of iron in both liver hepatocytes and Kupffer cells. The Kupffer cell response to this insult is two-fold: (1) the production of oxidative species-through both Kupffer cell activation and through the Fenton reaction involving iron and (2) the production of cytokines (for example TNF alpha). The induction of reactive oxygen species can, if not scavenged, produce oxidative DNA damage (the formation of OH8dG), as well as increase cell growth through modulation of gene expression. While the reactive oxygen species generation would occur in the both rats and mice, the ability of the rat to detoxify the reactive oxygen species would preclude the remaining steps from occurring. In contrast, in the mouse, the reactive oxygen species would override antioxidant defense mechanisms and allow the proposed mode of action to move forward. Our results to date in male B6C3F1 mice and male F344 rats treated with 2-butoxyethanol (via daily gavage; five times per week) at doses of 0, 225, 450, and 900 mg/kg/day (mice) and 0, 225, 450 mg/kg/day (rats), respectively, showed: an increase in hemolysis in 2-butoxyethanol treated rats and mice in a dose-dependent manner, in addition, an increase in the percent of iron stained Kupffer cells in the liver was observed following treatment with 450 and 900 mg/kg of 2-butoxyethanol in mice and 225 and 450 mg/kg of 2-butoxyethanol in rat. With the iron deposition, a biphasic increase in oxidative damage (OH8dG and malondialdehyde) was seen in mouse liver after treatment with 2-butoxyethanol. In contrast, no increase in oxidative damage was observed in the rat liver at any of the doses examined. Concomitant with the increase in oxidative damage, Vitamin E levels were similarly reduced by 2-butoxyethanol in both mice and rat liver. However, the basal level of Vitamin E in rat liver was 2.5-fold greater than in mouse liver. A biphasic induction of DNA synthesis was seen following 2-butoxyethanol in the mouse. In mouse liver, increased DNA synthesis was observed in hepatocytes at 90 days and in endothelial cells at 7 and 14 days at all doses. No change in DNA synthesis was seen in 2-butoxyethanol treated rat liver. No apparent differences in apoptosis and mitosis in the liver were observed in mouse and rat liver between 2-butoxyethanol treatment groups and untreated controls. These results suggest that the induction of DNA synthesis, possibly from oxidative stress and/or Kupffer cell activation, occurs selectively in the mouse liver, in endothelial cells and in hepatocytes following exposure to 2-butoxyethanol, and support the hypothesis proposed above.

Administration, Oral↗
PubMed1975

Studies of the erythron.

Radionuclide studies of the erythron are valuable to the physician in evaluating the clinical situation in a wide variety of hematologic disorders. A complete and accurate analysis of the life cycle of the red cell can be obtained with a full iron kinetic study, in conjunction with a DF32P red-cell survival study. However, a complete iron kinetic study is not always necessary. It may be abbreviated by deleting the in vitro phase of the iron kinetic procedure. The abbreviated iron kinetic study is also done in conjunction with a DF32P red-cell survival study. It can easily be performed by injecting 59Fe-labeled plasma and monitoring externally over the spleen, liver, and sacrum. Measurements of red-cell survival may be obtained with either 51Cr or DF32P. Although 51Cr provides a relatively uniform label of circulating red cells and is convenient to count in vitro, its highly variable elution rate precludes an accurate measurement of erythrocyte survival. The 51Cr method provides only a rough index of circulating red-cell half-times as a measure of red-cell survival. DF32P, HOWEVER, IS A PERMANENT LABEL OF CIRCULATING RED CELLS. It provides a direct measurement of erythrocyte survival and permits in vivo labeling of red cells simply by means of direct intravenous injection. Because it has an elution rate that is virtually zero after minimal elution on the day of injection, and because it is not reutilized, DF32P is unquestionably the best agent known for the determination of red-cell survival. In addition to these diagnostic data, the complete iron kinetic study can provide data on the deposition of iron in storage and the rate of iron storage exchange. It can also determine if erythropoiesis is quantitatively abnormal and if the abnormality is located in the bone marrow or in other organs such as the liver or spleen. Although the study of hematologic disorders is one of the most rapidly developing areas of medical research, techniques that are currently available can provide an understanding of the life cycle of the red cell and valuable data that can be applied directly to the clinical situation. When performed accurately, these studies provide a thorough analysis of the pathophysiology of the erythron and are valuable clinical tools that can be used successfully in the diagnosis and evaluation of a broad spectrum of hematological disorders.

Anemia↗
PubMed1975

Nuclear medicine and ultrasound; correlation in diagnosis of disease of liver and biliary tract.

Even though the radiocolloid scan is nonspecific it will be approximately 70%-80% accurate in predicting the presence or absence of liver disease and somewhat less accurate than that in making statements as to the specific type of disease. This compares well with other modalities. The ability of nuclear medicine techniques to provide a correct diagnosis is improved when additional isotopic techniques such as hepatic blood flow studies and 131I-rose bengal and 67Ga scanning are performed. Ultrasound scanning is also non specific. To date, the major application of ultrasound in the study of the liver has been in deciphering puzzling contour abnormalities seen on nuclear medicine scans and in demonstrating fluid-filled abnormalities. Its usefulness in diffuse and solid focal lesions has been less dramatic. More recently, however, the development of gray scale has necessitated a reevaluation of the technique. Gray scale demonstrates a large number of intrahepatic interfaces that were previously invisible, and it has already been shown to demonstrate focal disorders such as metastasis more easily than the nongray-scale method. It can also demonstrate dilated biliary radicals, the gallbladder, and gallstones. In addition, while routinely studying the liver one can evaluate diaphragmatic motion and various retroperitoneal structures such as the pancreas, lymph nodes, and abdominal vascular structures.

Adult↗
PubMed1977

Echocardiographic observations in patients with systemic infiltrative disease involving the heart.

Echocardiography was used to evaluate the heart in 19 patients with one of various systemic diseases known to be associated with infiltrative cardiomyopathy. Four patients had systemic amyloidosis, 10 had idiopathic hypereosinophilia and 5 had iron overload caused by multiple blood transfusions. Although 10 patients (53 percent) had no clinical evidence of cardiac disease, all 19 had echocardiographic abnormalities; the left ventricle was symmetrically thickened (more than 11 mm) and left ventricular mass was increased (more than 275 g) in all; the left ventricular transverse dimension was modestly increased (more than 52 mm) in 5 patients (26 percent) and the velocity of mitral valve closure in early diastole was reduced (less that 60 mm/sec) in 5 patients. Systolic function, as evidenced by ejection fraction, was well maintained (greater than 60 percent) in 18 of 19 patients. Thus, it appears that echocardiographic abnormalities can be detected in many patients with a systemic disease associated with infiltrative cardiomyopathy even before clinically evident heart disease develops.

Adult↗
PubMed1995

Iron overload in African Americans.

PURPOSE: Iron overload unexplained by dietary or medicinal iron excess, transfusion, or sideroblastic anemia has been described infrequently in Americans of African descent. The purpose of this study was to characterize iron overload attributable to excessive iron absorption in African Americans. PATIENTS AND METHODS: In a community hematology and medical oncology practice during the interval 1990 to 1993, we identified and evaluated a series of cases comprised of 6 men and 1 woman, with a mean age of 55 +/- 14 (SD) years (range 33 to 69). Data on clinical features, serum iron parameters, liver and body iron stores, evaluations of anemia, human leukocyte antigen (HLA) typing, and family studies were analyzed. RESULTS: Among our patients, the serum iron parameters were: iron concentration 26 +/- 13 mumol/L, transferrin saturation 59 +/- 21%, and ferritin concentration 1,588 +/- 1,053 micrograms/L. Clinical abnormalities observed included weakness and fatigue, decreased libido and impotence, hepatopathy, arthropathy, diabetes mellitus, hypogonadotrophic hypogonadism, and hyperpigmentation. Hepatic parenchymal cell iron deposits were increased in each of the 6 patients studied, and Kupffer cell iron deposits were prominent in 4. The occurrence of iron overload was verified by liver iron quantification and therapeutic phlebotomy. Four subjects had alpha-thalassemia minor; 2 others had hemoglobin S and C traits. No proband had HLA-A3 positivity. Four probands had other family members with iron overload. CONCLUSIONS: In comparison with Caucasians with hemochromatosis, our patients have slightly lower mean values of serum iron concentration and transferrin saturation, more Kupffer cell iron deposits, a higher incidence of thalassemia and hemoglobinopathy, and infrequent positivity for HLA-A3. Iron overload in African Americans appears to be more similar to that in certain sub-Saharan African natives than to hemochromatosis.

Adult↗
PubMed1979

The chest X-ray in pulmonary capillary haemorrhage: correlation with carbon monoxide uptake.

Serial changes in carbon monoxide uptake (KCO or DLCO/VA) were used to monitor episodes of pulmonary capillary haemorrhage in Goodpasture's syndrome (13 cases), immune complex nephritis (three cases) and idiopathic haemosiderosis (one case). Air-space shadowing on the chest X-ray (on a scoring system 0 to 12) was assessed in the light of the changes of KCO. In 14 out of 27 episodes of bleeding, the rise and fall of KCO was matched in time by the appearance and disappearance of air-space shadowing on the chest X-ray. In six episodes the chest X-ray remained normal despite a rise of KCO. In two cases air-space shadowing appeared up to 48 h after the rise of KCO. On five occasions chest X-ray abnormalities preceded the rise of KCO but chest infection or fluid overload accounted for three of these. In cases with suspected pulmonary capillary haemorrhage, measurements of carbon monoxide uptake will provide additional information and will assist in the interpretation of the chest X-ray.

Adolescent↗
PubMedDate not supplied

Secondary keratoconus with corneal epithelial iron ring similar to Fleischer's ring.

BACKGROUND: Fleischer's ring is considered to be a characteristic of keratoconus, but we have seen a ring similar to Fleischer's ring in patients with secondary keratoconus, in which the cornea becomes thinner secondarily for undetermined reasons. CASES: We report 6 cases of secondary keratoconus with a corneal epithelial ring similar to the Fleischer's ring pattern. OBSERVATIONS: In these 6 cases (2 men and 4 women), the causes of secondary keratoconus were trachoma in 2 cases, trauma in 2 cases, keratitis in 1 case and unknown etiology in one case. All showed thinning of the cornea and a corneal iron ring similar to Fleischer's ring pattern. The corneal button obtained after keratoplasty in 1 case showed the deposition of hemosiderin in the corneal epithelium after staining with Prussian blue. At the same time we confirmed the existence of iron in the corneal epithelium by x-ray ultimate analysis. CONCLUSIONS: All 6 patients we encountered had a past history of corneal disease in their childhood except for 1 case with unknown etiology. Primary keratoconus is also considered to develop by the early teens at the latest. These facts led us to an assumption that the occurrence of some abnormalities in the cornea during the growth period may result in iron deposition in the epithelium and thinning of the stroma. In light of these facts, abnormalities of the iron metabolism must be thoroughly investigated in considering the etiology of keratoconus.

Adult↗
PubMedDate not supplied

Pathology of toxoplasmosis in captive new world primates.

Clinical information was available for 32 of 33 New World primates with fatal toxoplasmosis, all of which were subjected to a variable number of pathological observations. Death without apparent clinical signs occurred in 43.7% of cases. The most common clinical findings were malaise (40.6%), dyspnoea (18.7%), hypothermia (15.6%) and a sero-sanguinous or foamy nasal discharge (12.5%). Nutritional status was good in 71.8%, average in 18.7% and poor in 9.4%. The most common post-mortem findings were pulmonary congestion (78.8%), pulmonary oedema (75.8%), splenomegaly (57.6%) and mesenteric lymphadenitis (54.6%). The most common histopathological findings were multifocal necrotic hepatitis (97%), lymphadenitis (95.4%), interstitial pneumonia (90.3%) and necrotic splenitis (71.4%). The gross post-mortem changes in cebids were more variable than those observed in callitrichids, a fact that may complicate the diagnosis of toxoplasmosis in cebids.

Animals↗